Cell-to-cell variation in gene expression and the aging process - Alexander R. Mendenhall; George M. Martin; Matt Kaeberlein; Rozalyn M. Anderson (GeroScience, 2021)

Aging, stress, and senescence in plants: what can biological diversity teach us? - Marina Pérez-Llorca; Sergi Munné-Bosch (GeroScience, 2021)

Are the 50’s, the transition decade, in choroid plexus aging? - Ana Tahira; Fernanda Marques; Bianca Lisboa; Arthur Feltrin; André Barbosa; Kátia Cristina de Oliveira; Carlos Alberto de Bragança Pereira; Renata Leite; Lea Grinberg; Claudia Suemoto; Renata Eloah de Lucena Ferretti-Rebustini; Carlos Augusto Pasqualucci; et al. (GeroScience, 2021)
The choroid plexus (CP) is an important structure for the brain. Besides its major role in the production of cerebrospinal fluid (CSF), it conveys signals originating from the brain, and from the circulatory system, shaping brain function in health and in pathology. Previous studies in rodents have revealed altered transcriptome both during aging and in various diseases of the central nervous system, including Alzheimer’s disease. In the present study, a high-throughput sequencing of the CP transcriptome was performed in postmortem samples of clinically healthy individuals aged 50’s through 80’s. The data shows an age-related profile, with the main changes occurring in the transition from the 50’s to the 60’s, stabilizing thereafter. Specifically, neuronal and membrane functions distinguish the transcriptome between the 50’s and the 60’s, while neuronal and axon development and extracellular structure organization differentiate the 50’s from the 70’s. These findings suggest that changes in the CP transcriptome occur early in the aging process. Future studies will unravel whether these relate with processes occurring in late- onset brain diseases.

Sex differences in the contribution of different physiological systems to physical function in older adults - Siana Jones; Martin G. Schultz; Therese Tillin; Chloe Park; Suzanne Williams; Nishi Chaturvedi; Alun D. Hughes (GeroScience, 2021)
Having the physical function to undertake activities of daily living (ADLs) is essential in order to maintain independence. The aim of this study is to investigate factors associated with physical function in older adults and determine if these associations differ in men versus women. In total, 726 participants (57% men; 73±7 years old) from a population-based cohort, the Southall and Brent Revisited (SABRE) study, completed questionnaires permitting a physical function score (PFS) to be calculated. Detailed phenotyping was performed including cardiovascular (echocardiography and macrovascular and microvascular functions), skeletal muscle (grip strength and oxidative capacity) and lung (pulmonary) function measurements. In a sub-group, maximal aerobic capacity was estimated from a sub-maximal exercise test. In women versus men, the association between grip strength and PFS was nearly 3 times stronger, and the association between microvascular dysfunction and PFS was over 5 times stronger (standardized β-coefficient (95% CI) 0.34 (0.22, 0.45) versus 0.11 (0.01,0.22) and −0.27 (−0.37, −0.17) versus −0.05 (−0.14, 0.04), respectively). In men, the association between cardiorespiratory fitness and PFS was 3 times greater than that in women (standardized β-coefficient (95% CI) 0.33 (0.22, 0.45) versus 0.10 (−0.04, 0.25). Cardiovascular, skeletal muscle and pulmonary factors all contribute to self-reported physical function, but the relative pattern of contribution differs by sex. Grip strength and microvascular function are most strongly associated with physical function in women while cardiorespiratory fitness is most strongly associated with physical function in men. This is relevant to the design of effective interventions that target maintenance of physical function in old age.

The impact of immuno-aging on SARS-CoV-2 vaccine development - Jennifer Connors; Matthew R. Bell; Jennifer Marcy; Michele Kutzler; Elias K. Haddad (GeroScience, 2021)

Alterations in the estrogen receptor profile of cardiovascular tissues during aging - Rakesh Gurrala; Isabella M. Kilanowski-Doroh; Dillion D. Hutson; Benard O. Ogola; Margaret A. Zimmerman; Prasad V. G. Katakam; Ryousuke Satou; Ricardo Mostany; Sarah H. Lindsey (GeroScience, 2021)

Effects of sleep deprivation on endothelial function in adult humans: a systematic review - Brady J. Holmer; Stephanie S. Lapierre; Danielle E. Jake-Schoffman; Demetra D. Christou (GeroScience, 2021)

Quest for a summary measure of biological age: the health and retirement study - Eileen M. Crimmins; Bharat Thyagarajan; Jung Ki Kim; David Weir; Jessica Faul (GeroScience, 2021)
Measures of biological age and its components have been shown to provide important information about individual health and prospective change in health as there is clear value in being able to assess whether someone is experiencing accelerated or decelerated aging. However, how to best assess biological age remains a question. We compare prediction of health outcomes using existing summary measures of biological age with a measure created by adding novel biomarkers related to aging to measures based on more conventional clinical chemistry and exam measures. We also compare the explanatory power of summary biological age measures compared to the individual biomarkers used to construct the measures. To accomplish this, we examine how well biological age, phenotypic age, and expanded biological age and five sets of individual biomarkers explain variability in four major health outcomes linked to aging in a large, nationally representative cohort of older Americans. We conclude that different summary measures of accelerated aging do better at explaining different health outcomes, and that chronological age has greater explanatory power for both cognitive dysfunction and mortality than the summary measures. In addition, we find that there is reduction in the variance explained in health outcomes when indicators are combined into summary measures, and that combining clinical indicators with more novel markers related to aging does best at explaining health outcomes. Finally, it is hard to define a set of assays that parsimoniously explains the greatest amount of variance across the range of health outcomes studied here. All of the individual markers considered were related to at least one of the health outcomes.

Recent advances and future avenues in understanding the role of adipose tissue cross talk in mediating skeletal muscle mass and function with ageing - Andrew Wilhelmsen; Kostas Tsintzas; Simon W. Jones (GeroScience, 2021)
Sarcopenia, broadly defined as the age-related decline in skeletal muscle mass, quality, and function, is associated with chronic low-grade inflammation and an increased likelihood of adverse health outcomes. The regulation of skeletal muscle mass with ageing is complex and necessitates a delicate balance between muscle protein synthesis and degradation. The secretion and transfer of cytokines, long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), both discretely and within extracellular vesicles, have emerged as important communication channels between tissues. Some of these factors have been implicated in regulating skeletal muscle mass, function, and pathologies and may be perturbed by excessive adiposity. Indeed, adipose tissue participates in a broad spectrum of inter-organ communication and obesity promotes the accumulation of macrophages, cellular senescence, and the production and secretion of pro-inflammatory factors. Pertinently, age-related sarcopenia has been reported to be more prevalent in obesity; however, such effects are confounded by comorbidities and physical activity level. In this review, we provide evidence that adiposity may exacerbate age-related sarcopenia and outline some emerging concepts of adipose-skeletal muscle communication including the secretion and processing of novel myokines and adipokines and the role of extracellular vesicles in mediating inter-tissue cross talk via lncRNAs and miRNAs in the context of sarcopenia, ageing, and obesity. Further research using advances in proteomics, transcriptomics, and techniques to investigate extracellular vesicles, with an emphasis on translational, longitudinal human studies, is required to better understand the physiological significance of these factors, the impact of obesity upon them, and their potential as therapeutic targets in combating muscle wasting.

Heterochronic blood exchange attenuates age-related neuroinflammation and confers cognitive benefits: do microvascular protective effects play a role? - Derek M. Huffman; Anna Csiszar; Zoltan Ungvari (GeroScience, 2021)

Correction to: Hydrogen sulfide ameliorates aging-associated changes in the kidney - Hak Joo Lee; Denis Feliers; Jeffrey L. Barnes; Sae Oh; Goutam Ghosh Choudhury; Vivian Diaz; Veronica Galvan; Randy Strong; James Nelson; Adam Salmon; Christopher G. Kevil; Balakuntalam S. Kasinath (GeroScience, 2021)

Level of the SARS-CoV-2 receptor ACE2 activity is highly elevated in old-aged patients with aortic stenosis: implications for ACE2 as a biomarker for the severity of COVID-19 - Miklós Fagyas; Attila Kertész; Ivetta Mányiné Siket; Viktor Bánhegyi; Bertalan Kracskó; Andrea Szegedi; Miklós Szokol; Gusztáv Vajda; Ildikó Rácz; Hajnalka Gulyás; Noémi Szkibák; Vivienn Rácz; et al. (GeroScience, 2021)
Coronavirus disease 2019 (COVID-19) has a high mortality in elderly patients with pre-existing cardiovascular diseases. The cellular receptor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the angiotensin-converting enzyme 2 (ACE2), thereby implicating a link between cardiovascular diseases and SARS-CoV-2 susceptibility. Aortic stenosis (AS) represents a chronic inflammatory state with severe cardiovascular complications in the elderly, a prime condition for COVID-19 mortality. The circulating ACE2 levels were measured in 111 patients with severe AS and compared to patients with hypertension and healthy individuals. About 4 times higher circulating ACE2 activity was found in patients with severe AS than in hypertensives or healthy individuals (88.3 ± 61.6., n = 111, 20.6 ± 13.4, n = 540, and 16.1 ± 7.4 mU/L, n = 46, respectively). Patients with severe AS were older than patients with hypertension (80 ± 6 years vs. 60 ± 15 years, P < 0.05). Serum ACE2 activity correlated negatively with the left ventricular ejection fraction, aortic root area, TAPSE, and positively with the right ventricular systolic pressure, cardiac diameters in patients with AS. In contrast, circulating ACE2 activity was independent of the blood pressure, peak flow velocity at the aortic root, kidney function (GFR), and inflammatory state (CRP). We found no effect of RAAS inhibitory drugs on the serum ACE2 activity in this group of patients. Our results illustrate circulating ACE2 as a potential interface between chronic inflammation, cardiovascular disease, and COVID-19 susceptibility. Elderly patients with AS have markedly elevated ACE2 levels together with altered left and right ventricular functions, which may pose higher risks during COVID-19. Our clinical data do not support a role for RAAS inhibitors in regulating circulating ACE2 levels.

Progression of neuropsychiatric symptoms in young-onset versus late-onset Alzheimer’s disease - Melisa Gumus; Namita Multani; Michael L. Mack; Maria Carmela Tartaglia (GeroScience, 2021)

Morbidity compression or expansion? A temporal analysis of the age at onset of non-communicable diseases in India - Sanjay K. Mohanty; Justin Rodgers; Rajeev R. Singh; Radhe Shyam Mishra; Rockli Kim; Junaid Khan; Priyamadhaba Behera; S. V. Subramanian (GeroScience, 2021)

Senescent cell accumulation mechanisms inferred from parabiosis - Omer Karin; Uri Alon (GeroScience, 2021)
Senescent cells are growth-arrested cells that cause inflammation and play a causal role in aging. They accumulate with age, and preventing this accumulation delays age-related diseases. However, the mechanism for senescent cell accumulation is not fully understood. Accumulation can result from increasing production or decreasing removal of senescent cells with age, or both. To distinguish between these possibilities, we analyze data from parabiosis, the surgical conjoining of two mice so that they share circulation. Parabiosis between a young and old mouse, called heterochronic parabiosis, reduces senescent cell levels in the old mouse, while raising senescent cell levels in the young mouse. We show that parabiosis data can reject mechanisms for senescent cell accumulation in which only production rises with age or only removal decreases with age; both must vary with age. Since removal drops with age, senescent cell half-life rises with age. This matches a recent model for senescent cell accumulation developed from independent data on senescent cell dynamics, called the SR model, in which production rises linearly with age and senescent cells inhibit their own removal. The SR model further explains the timescales and mechanism of rejuvenation in parabiosis, based on transfer of spare removal capacity from the young mouse to the old. The present quantitative understanding can help design optimal treatments that remove senescent cells, by matching the time between treatments to the time it takes senescent cells to re-accumulate.

Plasma dilution improves cognition and attenuates neuroinflammation in old mice - Melod Mehdipour; Taha Mehdipour; Colin M. Skinner; Nathan Wong; Chao Liu; Chia-Chien Chen; Ok Hee Jeon; Yi Zuo; Michael J. Conboy; Irina M. Conboy (GeroScience, 2021)
Our recent study has established that young blood factors are not causal, nor necessary, for the systemic rejuvenation of mammalian tissues. Instead, a procedure referred to as neutral blood exchange (NBE) that resets signaling milieu to a pro-regenerative state through dilution of old plasma, enhanced the health and repair of the muscle and liver, and promoted better hippocampal neurogenesis in 2-year-old mice (Mehdipour et al., Aging 12:8790–8819, 2020). Here we expand the rejuvenative phenotypes of NBE, focusing on the brain. Namely, our results demonstrate that old mice perform much better in novel object and novel texture (whisker discrimination) tests after a single NBE, which is accompanied by reduced neuroinflammation (less-activated CD68 + microglia). Evidence against attenuation/dilution of peripheral senescence-associated secretory phenotype (SASP) as the main mechanism behind NBE was that the senolytic ABT 263 had limited effects on neuroinflammation and did not enhance hippocampal neurogenesis in the old mice. Interestingly, peripherally acting ABT 263 and NBE both diminished SA-βGal signal in the old brain, demonstrating that peripheral senescence propagates to the brain, but NBE was more robustly rejuvenative than ABT 263, suggesting that rejuvenation was not simply by reducing senescence. Explaining the mechanism of the positive effects of NBE on the brain, our comparative proteomics analysis demonstrated that dilution of old blood plasma yields an increase in the determinants of brain maintenance and repair in mice and in people. These findings confirm the paradigm of rejuvenation through dilution of age-elevated systemic factors and extrapolate it to brain health and function.

Comparison of clinical characteristics of patients with pandemic SARS-CoV-2-related and community-acquired pneumonias in Hungary – a pilot historical case-control study - Viktor J. Horváth; Noémi Hajdú; Orsolya Vági; Karolina Schnábel; Emese Szelke; Anna E. Körei; Magdolna Békeffy; Márk M. Svébis; Beatrix A. Domján; Tamás Berényi; István Takács; Zoltán Ungvári; et al. (GeroScience, 2021)
The distinction between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–related and community-acquired pneumonias poses significant difficulties, as both frequently involve the elderly. This study aimed to predict the risk of SARS-CoV-2-related pneumonia based on clinical characteristics at hospital presentation. Case-control study of all patients admitted for pneumonia at Semmelweis University Emergency Department. Cases ( n = 30) were patients diagnosed with SARS-CoV-2-related pneumonia (based on polymerase chain reaction test) between 26 March 2020 and 30 April 2020; controls ( n = 82) were historical pneumonia cases between 1 January 2019 and 30 April 2019. Logistic models were built with SARS-CoV-2 infection as outcome using clinical characteristics at presentation. Patients with SARS-CoV-2-related pneumonia were younger (mean difference, 95% CI: 9.3, 3.2–15.5 years) and had a higher lymphocyte count, lower C-reactive protein, presented more frequently with bilateral infiltrate, less frequently with abdominal pain, diarrhoea, and nausea in age- and sex-adjusted models. A logistic model using age, sex, abdominal pain, C-reactive protein, and the presence of bilateral infiltrate as predictors had an excellent discrimination (AUC 0.88, 95% CI: 0.81–0.96) and calibration ( p = 0.27–Hosmer-Lemeshow test). The clinical use of our screening prediction model could improve the discrimination of SARS-CoV-2 related from other community-acquired pneumonias and thus help patient triage based on commonly used diagnostic approaches. However, external validation in independent datasets is required before its clinical use.

Whole brain irradiation in mice causes long-term impairment in astrocytic calcium signaling but preserves astrocyte-astrocyte coupling - Adam Institoris; Ciaran Murphy-Royal; Stefano Tarantini; Andriy Yabluchanskiy; Jordan N. Haidey; Anna Csiszar; Zoltan Ungvari; Grant R. Gordon (GeroScience, 2021)

“Cerebral small vessel disease and other influential factors of cognitive impairment in the middle-aged: a long-term observational cohort PURE-MIND study in Poland” - Dorota Szcześniak; Joanna Rymaszewska; Anna Zimny; Marek Sąsiadek; Katarzyna Połtyn-Zaradna; Eric E. Smith; Katarzyna Zatońska; Tomasz Zatoński; Sumathy Rangarajan; Salim Yusuf; Andrzej Szuba (GeroScience, 2021)
A complex picture of factors influencing cognition is necessary to be drawn for a better understanding of the role of potentially modifiable factors in dementia. The aim was to assess the prevalence and determinants of cognitive impairment, including the role of cerebral small vessel disease (CSVD) in Polish middle-aged cohort. A comprehensive set of clinical (hypertension, coronary heart disease, diabetes mellitus, hyperlipidaemia, body mass index, smoking status, alcohol intake) and socio-demographic data was collected in the PURE study in years 2007–2016, which was the basis for detailed analysis of risk factors of cognitive impairments in years 2016–2018 in the PURE-MIND sub-study. Five hundred forty-seven subjects (age range 39–65, mean 56.2 ± 6.5) underwent neuropsychological assessment with Montreal Cognitive Assessment (MoCA), Trail Making Test (TMT) and Digit Symbol Substitution Test (DSST) followed by brain MRI. Mean MoCA score was 26.29 and 33% participants met criteria for mild cognitive impairment (MCI) (MoCA< 26). Seventy-three percent showed findings related to CSVD. Higher WMH burden and lacunar infarcts were associated with lower MoCA and DSST scores. Severe CSVD was associated with twofold incidence of MCI, and obesity increased its probability by 53% and hypertension by 37%. The likelihood of MCI was reduced in nonsmokers. One factor analysis showed the important role of lower level of education, older age, rural area of residence and hypertension. MCI and CSVD are highly prevalent in the middle-aged population in Poland. A greater importance should be given to potentially modifiable risk factors of dementia which are already present in mid-life.

Quality of life after traumatic brain injury: a cross-sectional analysis uncovers age- and sex-related differences over the adult life span - Katrin Rauen; Claudia B. Späni; Maria Carmela Tartaglia; Maria Teresa Ferretti; Lara Reichelt; Philipp Probst; Barbara Schäpers; Friedemann Müller; Klaus Jahn; Nikolaus Plesnila (GeroScience, 2021)
Traumatic brain injury (TBI) is the leading cause of disability in the working population and becomes increasingly prevalent in the elderly. Thus, TBI is a major global health burden. However, age- and sex-related long-term outcome regarding patient’s health-related quality of life (HRQoL) is yet not clarified. In this cross-sectional study, we present age- and sex-related demographics and HRQoL up to 10 years after TBI using the Quality of Life after Brain Injury (QOLIBRI) instrument. The QOLIBRI total score ranges from zero to 100 indicating good (≥ 60), moderate (40–59) or unfavorable (< 40) HRQoL. Two-thirds of the entire chronic TBI cohort (102 males; 33 females) aged 18–85 years reported good HRQoL up to 10 years after TBI. TBI etiology differed between sexes with females suffering more often from traffic- than fall-related TBI ( p = 0.01) with increasing prevalence during aging ( p = < 0.001). HRQoL (good/moderate/unfavorable) differed between sexes ( p < 0.0001) with 17% more females reporting moderate outcome ( p = 0.01). Specifically, older females (54–76-years at TBI) were affected, while males constantly reported good HRQoL ( p = 0.017). Cognition ( p = 0.014), self-perception ( p = 0.009), and emotions ( p = 0.016) rather than physical problems ( p = 0.1) constrained older females’ HRQoL after TBI. Experiencing TBI during aging does not influence HRQoL outcome in males but females suggesting that female brains cope less well with a traumatic injury during aging. Therefore, older females need long-term follow-ups after TBI to detect neuropsychiatric sequels that restrict their quality of life. Further investigations are necessary to uncover the mechanisms of this so far unknown phenomenon.

Internalize at your peril: internalizing disorders as risk factors for dementia—cohort study - Yoram Barak; David Barson; Gabrielle Davie; Paul Glue; Diana Paleacu (GeroScience, 2021)

Primary neuron and astrocyte cultures from postnatal Callithrix jacchus: a non-human primate in vitro model for research in neuroscience, nervous system aging, and neurological diseases of aging - Angela O. Dorigatti; Stacy A. Hussong; Stephen F. Hernandez; Aubrey M. Sills; Adam B. Salmon; Veronica Galvan (GeroScience, 2021)

Association of physical activity and sedentary time with structural brain networks—The Maastricht Study - Laura W. M. Vergoossen; J. F. A. Jansen; J. J. A. de Jong; C. D. A. Stehouwer; N. C. Schaper; H. H. C. M. Savelberg; A. Koster; W. H. Backes; M. T. Schram (GeroScience, 2021)
We assessed whether objectively measured low- and high-intensity physical activity (LPA and HPA) and sedentary time (ST) were associated with white matter connectivity, both throughout the whole brain and in brain regions involved in motor function. In the large population-based Maastricht Study ( n = 1715, age 59.6 ± 8.1 (mean ± standard deviation) years, and 48% women), the amounts of LPA, HPA, and ST were objectively measured during 7 days by an activPAL accelerometer. In addition, using 3T structural and diffusion MRI, we calculated whole brain node degree and node degree of the basal ganglia and primary motor cortex. Multivariable linear regression analysis was performed, and we report standardized regression coefficients (stβ) adjusted for age, sex, education level, wake time, diabetes status, BMI, office systolic blood pressure, antihypertensive medication, total-cholesterol-to-HDL-cholesterol ratio, lipid-modifying medication, alcohol use, smoking status, and history of cardiovascular disease. Lower HPA was associated with lower whole brain node degree after full adjustment (stβ [95%CI] = − 0.062 [− 0.101, − 0.013]; p = 0.014), whereas lower LPA (stβ [95%CI] = − 0.013 [− 0.061, 0.034]; p = 0.580) and higher ST (stβ [95%CI] = − 0.030 [− 0.081, 0.021]; p = 0.250) was not. In addition, lower HPA was associated with lower node degree of the basal ganglia after full adjustment (stβ [95%CI] = − 0.070 [− 0.121, − 0.018]; p = 0.009). Objectively measured lower HPA, but not lower LPA and higher ST, was associated with lower whole brain node degree and node degree in specific brain regions highly specialized in motor function. Further research is needed to establish whether more HPA may preserve structural brain connectivity.

Traumatic brain injury-induced cerebral microbleeds in the elderly - Luca Toth; Andras Czigler; Peter Horvath; Balint Kornyei; Nikolett Szarka; Attila Schwarcz; Zoltan Ungvari; Andras Buki; Peter Toth (GeroScience, 2021)
Traumatic brain injury (TBI) was shown to lead to the development of cerebral microbleeds (CMBs), which are associated with long term cognitive decline and gait disturbances in patients. The elderly is one of the most vulnerable parts of the population to suffer TBI. Importantly, ageing is known to exacerbate microvascular fragility and to promote the formation of CMBs. In this overview, the effect of ageing is discussed on the development and characteristics of TBI-related CMBs, with special emphasis on CMBs associated with mild TBI. Four cases of TBI-related CMBs are described to illustrate the concept that ageing exacerbates the deleterious microvascular effects of TBI and that similar brain trauma may induce more CMBs in old patients than in young ones. Recommendations are made for future prospective studies to establish the mechanistic effects of ageing on the formation of CMBs after TBI, and to determine long-term consequences of CMBs on clinically relevant outcome measures including cognitive performance, gait and balance function.

HIV-1 Tat promotes age-related cognitive, anxiety-like, and antinociceptive impairments in female mice that are moderated by aging and endocrine status - Alaa N. Qrareya; Fakhri Mahdi; Marc J. Kaufman; Nicole M. Ashpole; Jason J. Paris (GeroScience, 2021)

Estrogen receptor involvement in vascular cognitive impairment and vascular dementia pathogenesis and treatment - Dianna H. Nguyen; J. Thomas Cunningham; Nathalie Sumien (GeroScience, 2021)

A short digital eye-tracking assessment predicts cognitive status among adults - Joshua L. Gills; Nick T. Bott; Erica N. Madero; Jordan M. Glenn; Michelle Gray (GeroScience, 2021)

The gut microbiome–derived metabolite trimethylamine N-oxide modulates neuroinflammation and cognitive function with aging - Vienna E. Brunt; Thomas J. LaRocca; Amy E. Bazzoni; Zachary J. Sapinsley; Jill Miyamoto-Ditmon; Rachel A. Gioscia-Ryan; Andrew P. Neilson; Christopher D. Link; Douglas R. Seals (GeroScience, 2021)

Contribution of Porphyromonas gingivalis lipopolysaccharide to experimental periodontitis in relation to aging - Juliet Akkaoui; Chiaki Yamada; Carolina Duarte; Anny Ho; Saynur Vardar-Sengul; Toshihisa Kawai; Alexandru Movila (GeroScience, 2021)

A chemical biology approach to identifying molecular pathways associated with aging - Antonio Currais; Ling Huang; Michael Petrascheck; Pamela Maher; David Schubert (GeroScience, 2021)

Biomarkers of senescence in non-human primate adipose depots relate to aging - Kylie Kavanagh; Chrissy Sherrill; Alistaire Ruggiero; Masha Block; Ravichandra Vemuri; Matthew Davis; Amanda Olivier (GeroScience, 2021)

Muscle from aged rats is resistant to mechanotherapy during atrophy and reloading - Marcus M. Lawrence; Douglas W. Van Pelt; Amy L. Confides; Zachary R. Hettinger; Emily R. Hunt; Justin J. Reid; Jaime L. Laurin; Frederick F. Peelor; Timothy A. Butterfield; Benjamin F. Miller; Esther E. Dupont-Versteegden (GeroScience, 2021)

Late-life voluntary wheel running reverses age-related aortic stiffness in mice: a translational model for studying mechanisms of exercise-mediated arterial de-stiffening - Rachel A. Gioscia-Ryan; Zachary S. Clayton; Bradley S. Fleenor; Jason S. Eng; Lawrence C. Johnson; Matthew J. Rossman; Melanie C. Zigler; Trent D. Evans; Douglas R. Seals (GeroScience, 2021)

The coming of age of AGE - Aubrey D. N. J. de Grey (GeroScience, 2020)

Longitudinal trends in master track and field performance throughout the aging process: 83,209 results from Sweden in 16 athletics disciplines - Bergita Ganse; Anthony Kleerekoper; Matthias Knobe; Frank Hildebrand; Hans Degens (GeroScience, 2020)
In the research of age-related performance declines, the value of cross-sectional versus longitudinal data is an ongoing debate. This paper analyses the largest longitudinal master track and field data set ever published to compare the age-related decline in performance between 16 athletics disciplines in cross-sectional and longitudinal data. The data set contained 83,209 results (64,948 from men, 78.1%; 18,261 from women, 21.9%) from 34,132 athletes (26,186 men, 76.7%; 7946 women, 23.3%), aged 35–97 years. In 61 athletes, 20 or more, and in 312 athletes, 15 or more results were available. The data were analyzed by regression statistics/ANCOVA. Men had a higher performance than women, irrespective of discipline in both cross-sectional and longitudinal data ( p < 0.001). The performance in cross-sectional data was lower compared with the longitudinal data in all events and at any age ( p ≤ 0.007) except for 1000 m men. The average age was lower in the cross-sectional than the longitudinal data ( p < 0.001); men 46 and 58 years, women 44 and 56 years, respectively. The annual percentage rate of decline did not differ significantly between cross-sectional and longitudinal data, or between sexes in most disciplines. Performance declines after age 70 were 1.7 times (men) and 1.4 times (women) as steep as before. In conclusion, although longitudinal master athletics data of athletes with 10 and more results has higher average performance and age compared with cross-sectional data, cross-sectional data give a good impression of the annual percentage decline in performance, which was similar in men and women.

Candidate rejuvenating factor GDF11 and tissue fibrosis: friend or foe? - Jan Frohlich; Manlio Vinciguerra (GeroScience, 2020)

Imaging the role of blood–brain barrier disruption in normal cognitive ageing - Inge C. M. Verheggen; Joost J. A. de Jong; Martin P. J. van Boxtel; Alida A. Postma; Jacobus F. A. Jansen; Frans R. J. Verhey; Walter H. Backes (GeroScience, 2020)
To investigate whether blood–brain barrier (BBB) disruption is a potential mechanism of usual age-related cognitive decline, we conducted dynamic contrast–enhanced (DCE) MRI to measure BBB leakage in a healthy sample, and investigated the association with longitudinal cognitive decline. In a sample of neurologically and cognitively healthy, older individuals, BBB leakage rate in the white and grey matter and hippocampus was measured using DCE MRI with pharmacokinetic modelling. Regression analysis was performed to investigate whether the leakage rate was associated with decline in cognitive performance (memory encoding, memory retrieval, executive functioning and processing speed) over 12 years. White and grey matter BBB leakages were significantly associated with decline in memory retrieval. No significant relations were found between hippocampal BBB leakage and cognitive performance. BBB disruption already being associated with usual cognitive ageing, supports that this neurovascular alteration is a possible explanation for the cognitive decline inherent to the ageing process. More insight into BBB leakage during the normal ageing process could improve estimation and interpretation of leakage rate in pathological conditions. The current results might also stimulate the search for strategies to maintain BBB integrity and help increase the proportion people experiencing successful ageing. Netherlands Trial Register number: NL6358, date of registration: 2017-03-24.

Retinal biomarkers for Alzheimer’s disease and vascular cognitive impairment and dementia (VCID): implication for early diagnosis and prognosis - Cecilia Czakó; Tibor Kovács; Zoltan Ungvari; Anna Csiszar; Andriy Yabluchanskiy; Shannon Conley; Tamas Csipo; Agnes Lipecz; Hajnalka Horváth; Gábor László Sándor; Lilla István; Trevor Logan; et al. (GeroScience, 2020)
Cognitive impairment and dementia are major medical, social, and economic public health issues worldwide with significant implications for life quality in older adults. The leading causes are Alzheimer’s disease (AD) and vascular cognitive impairment/dementia (VCID). In both conditions, pathological alterations of the cerebral microcirculation play a critical pathogenic role. Currently, the main pathological biomarkers of AD—β-amyloid peptide and hyperphosphorylated tau proteins—are detected either through cerebrospinal fluid (CSF) or PET examination. Nevertheless, given that they are invasive and expensive procedures, their availability is limited. Being part of the central nervous system, the retina offers a unique and easy method to study both neurodegenerative disorders and cerebral small vessel diseases in vivo. Over the past few decades, a number of novel approaches in retinal imaging have been developed that may allow physicians and researchers to gain insights into the genesis and progression of cerebromicrovascular pathologies. Optical coherence tomography (OCT), OCT angiography, fundus photography, and dynamic vessel analyzer (DVA) are new imaging methods providing quantitative assessment of retinal structural and vascular indicators—such as thickness of the inner retinal layers, retinal vessel density, foveal avascular zone area, tortuosity and fractal dimension of retinal vessels, and microvascular dysfunction—for cognitive impairment and dementia. Should further studies need to be conducted, these retinal alterations may prove to be useful biomarkers for screening and monitoring dementia progression in clinical routine. In this review, we seek to highlight recent findings and current knowledge regarding the application of retinal biomarkers in dementia assessment.

Sarcopenia during COVID-19 lockdown restrictions: long-term health effects of short-term muscle loss - Richard Kirwan; Deaglan McCullough; Tom Butler; Fatima Perez de Heredia; Ian G. Davies; Claire Stewart (GeroScience, 2020)
The COVID-19 pandemic is an extraordinary global emergency that has led to the implementation of unprecedented measures in order to stem the spread of the infection. Internationally, governments are enforcing measures such as travel bans, quarantine, isolation, and social distancing leading to an extended period of time at home. This has resulted in reductions in physical activity and changes in dietary intakes that have the potential to accelerate sarcopenia, a deterioration of muscle mass and function (more likely in older populations), as well as increases in body fat. These changes in body composition are associated with a number of chronic, lifestyle diseases including cardiovascular disease (CVD), diabetes, osteoporosis, frailty, cognitive decline, and depression. Furthermore, CVD, diabetes, and elevated body fat are associated with greater risk of COVID-19 infection and more severe symptomology, underscoring the importance of avoiding the development of such morbidities. Here we review mechanisms of sarcopenia and their relation to the current data on the effects of COVID-19 confinement on physical activity, dietary habits, sleep, and stress as well as extended bed rest due to COVID-19 hospitalization. The potential of these factors to lead to an increased likelihood of muscle loss and chronic disease will be discussed. By offering a number of home-based strategies including resistance exercise, higher protein intakes and supplementation, we can potentially guide public health authorities to avoid a lifestyle disease and rehabilitation crisis post-COVID-19. Such strategies may also serve as useful preventative measures for reducing the likelihood of sarcopenia in general and in the event of future periods of isolation.

Semiautomatic morphometric analysis of skeletal muscle obtained by needle biopsy in older adults - Henry J. Bonilla; Maria L. Messi; Khalima A. Sadieva; Craig A. Hamilton; Aron S. Buchman; Osvaldo Delbono (GeroScience, 2020)

Correction to: Reflections on designing population surveys for COVID-19 infection and prevalence - Akshay Swaminathan; S. V. Subramanian (GeroScience, 2020)

A multivariate model of time to conversion from mild cognitive impairment to Alzheimer’s disease - María Eugenia López; Agustín Turrero; Pablo Cuesta; Inmaculada Concepción Rodríguez-Rojo; Ana Barabash; Alberto Marcos; Fernando Maestú; Alberto Fernández (GeroScience, 2020)

Amyloidosis increase is not attenuated by long-term calorie restriction or related to neuron density in the prefrontal cortex of extremely aged rhesus macaques - GA Stonebarger; HF Urbanski; RL Woltjer; KL Vaughan; DK Ingram; PL Schultz; SM Calderazzo; JA Siedeman; JA Mattison; DL Rosene; SG Kohama (GeroScience, 2020)

Increases in hypertension-induced cerebral microhemorrhages exacerbate gait dysfunction in a mouse model of Alzheimer’s disease - Ádám Nyúl-Tóth; Stefano Tarantini; Tamas Kiss; Peter Toth; Veronica Galvan; Amber Tarantini; Andriy Yabluchanskiy; Anna Csiszar; Zoltan Ungvari (GeroScience, 2020)

Reflections on designing population surveys for COVID-19 infection and prevalence - Akshay Swaminathan; S. V. Subramanian (GeroScience, 2020)

Association of inflammatory mediators with frailty status in older adults: results from a systematic review and meta-analysis - Diego Marcos-Pérez; María Sánchez-Flores; Stefania Proietti; Stefano Bonassi; Solange Costa; Joao Paulo Teixeira; Juan Fernández-Tajes; Eduardo Pásaro; Blanca Laffon; Vanessa Valdiglesias (GeroScience, 2020)

Decline in endothelial function across the menopause transition in healthy women is related to decreased estradiol and increased oxidative stress - Kerrie L. Moreau; Kerry L. Hildreth; Jelena Klawitter; Patrick Blatchford; Wendy M. Kohrt (GeroScience, 2020)

Integrated metabolomics reveals altered lipid metabolism in adipose tissue in a model of extreme longevity - Justin Darcy; Yimin Fang; Samuel McFadden; Matthew D. Lynes; Luiz O. Leiria; Jonathan M. Dreyfuss; Valerie Bussburg; Vladimir Tolstikov; Bennett Greenwood; Niven R. Narain; Michael A. Kiebish; Andrzej Bartke; et al. (GeroScience, 2020)

Development of a cyclophosphamide stress test to predict resilience to aging in mice - Lida Zhu; Yan Dou; Marianne Bjorner; Warren Ladiges (GeroScience, 2020)

eIF4E phosphorylation modulates pain and neuroinflammation in the aged - Prapti H. Mody; Natalia L. Dos Santos; Luz R. Barron; Theodore J. Price; Michael D. Burton (GeroScience, 2020)

Advanced maternal age impacts physiologic adaptations to pregnancy in vervet monkeys - Maren Plant; Cecilia Armstrong; Alistaire Ruggiero; Chrissy Sherrill; Beth Uberseder; Rachel Jeffries; Justin Nevarez; Matthew J. Jorgensen; Kylie Kavanagh; Matthew A. Quinn (GeroScience, 2020)

Polygenic risk scores: pleiotropy and the effect of environment - Yury Loika; Irina Irincheeva; Irina Culminskaya; Alireza Nazarian; Alexander M. Kulminski (GeroScience, 2020)

Vaccination mitigates influenza-induced muscular declines in aged mice - Spencer R. Keilich; Erica C. Lorenzo; Blake L. Torrance; Andrew G. Harrison; Jenna M. Bartley; Laura Haynes (GeroScience, 2020)

Superoxide-mediated oxidative stress accelerates skeletal muscle atrophy by synchronous activation of proteolytic systems - Young C. Jang; Karl Rodriguez; Michael S. Lustgarten; Florian L. Muller; Arunabh Bhattacharya; Anson Pierce; Jeongmoon J. Choi; Nan Hee Lee; Asish Chaudhuri; Arlan G. Richardson; Holly Van Remmen (GeroScience, 2020)

Hypoxic response regulators RHY-1 and EGL-9/PHD promote longevity through a VHL-1-independent transcriptional response - Joseph C.P. Kruempel; Hillary A. Miller; Megan L. Schaller; Abrielle Fretz; Marshall Howington; Marjana Sarker; Shijiao Huang; Scott F. Leiser (GeroScience, 2020)

A summary of the Proceedings of the Fourteenth International Symposium on the Neurobiology and Neuroendocrinology of Aging, Bregenz, Austria July 15-20, 2018 - Holly M. Brown-Borg; Kurt E. Borg (GeroScience, 2020)

Cardiovascular fitness and structural brain integrity: an update on current evidence - Tracy d’Arbeloff (GeroScience, 2020)

Role of B cells and the aging brain in stroke recovery and treatment - E. B. Engler-Chiurazzi; K. L. Monaghan; E. C. K. Wan; X. Ren (GeroScience, 2020)

Companion animals likely do not spread COVID-19 but may get infected themselves - Anna Csiszar; Ferenc Jakab; Teresa G. Valencak; Zsófia Lanszki; Gábor Endre Tóth; Gábor Kemenesi; Stefano Tarantini; Vince Fazekas-Pongor; Zoltan Ungvari (GeroScience, 2020)

Sleep, brain vascular health and ageing - Arehally M. Mahalakshmi; Bipul Ray; Sunanda Tuladhar; Abid Bhat; Muhammed Bishir; Srinivasa Rao Bolla; Jian Yang; Musthafa Mohamed Essa; Saravana Babu Chidambaram; Gilles J. Guillemin; Meena Kishore Sakharkar (GeroScience, 2020)

Acute cognitive deficits after traumatic brain injury predict Alzheimer’s disease-like degradation of the human default mode network - Andrei Irimia; Alexander S. Maher; Nikhil N. Chaudhari; Nahian F. Chowdhury; Elliot B. Jacobs (GeroScience, 2020)

An evaluation of the SARS-CoV-2 epidemic 16 days after the end of social confinement in Hungary - Veronica Galvan; Jorge Quarleri (GeroScience, 2020)

Learning from success: how has Hungary responded to the COVID pandemic? - Martin McKee (GeroScience, 2020)

New view on older adults with COVID-19: comments on “SARS-CoV-2 and COVID-19 in older adults: what we may expect regarding pathogenesis, immune responses, and outcomes” - Gang Xu; Min Ye; Jun Zhao; Feng Liu; Wei Ma (GeroScience, 2020)

Brain angiotensin II and angiotensin IV receptors as potential Alzheimer’s disease therapeutic targets - Jessika Royea; Edith Hamel (GeroScience, 2020)

Aging exacerbates impairments of cerebral blood flow autoregulation and cognition in diabetic rats - Shaoxun Wang; Wenshan Lv; Huawei Zhang; Yedan Liu; Longyang Li; Joshua R. Jefferson; Ya Guo; Man Li; Wenjun Gao; Xing Fang; Ian A. Paul; Grazyna Rajkowska; et al. (GeroScience, 2020)

The relationship of parental longevity with the aging brain—results from UK Biobank - Qu Tian; Luke C. Pilling; Janice L. Atkins; David Melzer; Luigi Ferrucci (GeroScience, 2020)

Seropositivity for pathogens associated with chronic infections is a risk factor for all-cause mortality in the elderly: findings from the Memory and Morbidity in Augsburg Elderly (MEMO) Study - Marius Zeeb; Tobias Kerrinnes; Luka Cicin-Sain; Carlos A. Guzman; Wolfram Puppe; Thomas F. Schulz; Annette Peters; Klaus Berger; Stefanie Castell; André Karch (GeroScience, 2020)
Immunostimulation by chronic infection has been linked to an increased risk for different non-communicable diseases, which in turn are leading causes of death in high- and middle-income countries. Thus, we investigated if a positive serostatus for pathogens responsible for common chronic infections is individually or synergistically related to reduced overall survival in community dwelling elderly. We used data of 365 individuals from the German MEMO (Memory and Morbidity in Augsburg Elderly) cohort study with a median age of 73 years at baseline and a median follow-up of 14 years. We examined the effect of a positive serostatus at baseline for selected pathogens associated with chronic infections ( Helicobacter pylori , Borrelia burgdorferi sensu lato , Toxoplasma gondii , cytomegalovirus, Epstein-Barr virus, herpes simplex virus 1/2, and human herpesvirus 6) on all-cause mortality with multivariable parametric survival models. We found a reduced survival time in individuals with a positive serostatus for Helicobacter pylori (accelerated failure time (AFT) − 15.92, 95% CI − 29.96; − 1.88), cytomegalovirus (AFT − 22.81, 95% CI − 36.41; − 9.22) and Borrelia burgdorferi sensu lato (AFT − 25.25, 95% CI − 43.40; − 7.10), after adjusting for potential confounders. The number of infectious agents an individual was seropositive for had a linear effect on all-cause mortality (AFT per additional infection − 12.42 95% CI − 18.55; − 6.30). Our results suggest an effect of seropositivity for Helicobacter pylori , cytomegalovirus, and Borrelia burgdorferi sensu lato on all-cause mortality in older community dwelling individuals. Further research with larger cohorts and additional biomarkers is required, to assess mediators and molecular pathways of this effect.

Common transcriptome, plasma molecules, and imaging signatures in the aging brain and a Mendelian neurovascular disease, cerebral cavernous malformation - Janne Koskimäki; Sean P. Polster; Yan Li; Sharbel Romanos; Abhinav Srinath; Dongdong Zhang; Julián Carrión-Penagos; Rhonda Lightle; Thomas Moore; Seán B. Lyne; Agnieszka Stadnik; Kristina Piedad; et al. (GeroScience, 2020)

Patterns of multi-domain cognitive aging in participants of the Long Life Family Study - Paola Sebastiani; Stacy L. Andersen; Benjamin Sweigart; Mengtian Du; Stephanie Cosentino; Bharat Thyagarajan; Kaare Christensen; Nicole Schupf; Thomas T Perls (GeroScience, 2020)

A novel multi-marker discovery approach identifies new serum biomarkers for Parkinson’s disease in older people: an EXosomes in PArkiNson Disease (EXPAND) ancillary study - Riccardo Calvani; Anna Picca; Giovanni Landi; Federico Marini; Alessandra Biancolillo; Hélio José Coelho-Junior; Jacopo Gervasoni; Silvia Persichilli; Aniello Primiano; Annalaura Arcidiacono; Andrea Urbani; Maurizio Bossola; et al. (GeroScience, 2020)

Angiotensin (1–7) delivered orally via probiotic, but not subcutaneously, benefits the gut-brain axis in older rats - Thomas W. Buford; Yi Sun; Lisa M. Roberts; Anisha Banerjee; Sujitha Peramsetty; Anthony Knighton; Amrisha Verma; Drake Morgan; Gonzalo E. Torres; Qiuhong Li; Christy S. Carter (GeroScience, 2020)

Novel coronavirus epidemic in the Hungarian population, a cross-sectional nationwide survey to support the exit policy in Hungary - Béla Merkely; Attila J. Szabó; Annamária Kosztin; Ervin Berényi; Andor Sebestyén; Csaba Lengyel; Gergő Merkely; Júlia Karády; István Várkonyi; Csaba Papp; Attila Miseta; József Betlehem; et al. (GeroScience, 2020)
After months of restrictive containment efforts to fight the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) epidemic, European countries are planning to reopen. To support the process, we conducted a cross-sectional survey among the Hungarian population to estimate the prevalence of infectious cases and prior SARS-CoV-2 exposure. A representative sample ( n = 17,787) for the Hungarian population of 14 years or older living in private households ( n = 8,283,810) was selected. The study was performed within 16 days after 50 days of restrictions, when the number of confirmed cases was stable low. Naso- and oropharyngeal smears and blood samples were collected for PCR and antibody testing. The testing was accompanied by a questionnaire about symptoms, comorbidities, and contacts. Design-based prevalence estimates were calculated. In total, 10,474 individuals (67.7% taken into account a sample frame error of 2315) of the selected sample participated in the survey. Of the tested individuals, 3 had positive PCR and 69 had positive serological test. Population estimate of the number of SARS-CoV-2 infection and seropositivity were 2421 and 56,439, respectively, thus active infection rate (2.9/10,000) and the prevalence of prior SARS-CoV-2 exposure (68/10,000) was low. Self-reported loss of smell or taste and body aches were significantly more frequent among those with SARS-CoV-2. In this representative, cross-sectional survey of the Hungarian population with a high participation rate, the overall active infection rate was low in sync with the prevalence of prior SARS-CoV-2 exposure. We demonstrated a potential success of containment efforts, supporting an exit strategy. NCT04370067, 30.04.2020.

Increase in blood–brain barrier leakage in healthy, older adults - Inge C. M. Verheggen; Joost J. A. de Jong; Martin P. J. van Boxtel; Ed H. B. M. Gronenschild; Walter M. Palm; Alida A. Postma; Jacobus F. A. Jansen; Frans R. J. Verhey; Walter H. Backes (GeroScience, 2020)
Blood–brain barrier (BBB) breakdown can disrupt nutrient supply and waste removal, which affects neuronal functioning. Currently, dynamic contrast-enhanced (DCE) MRI is the preferred in-vivo method to quantify BBB leakage. Dedicated DCE MRI studies in normal aging individuals are lacking, which could hamper value estimation and interpretation of leakage rate in pathological conditions. Therefore, we applied DCE MRI to investigate the association between BBB disruption and age in a healthy sample. Fifty-seven cognitively and neurologically healthy, middle-aged to older participants (mean age: 66 years, range: 47–91 years) underwent MRI, including DCE MRI with intravenous injection of a gadolinium-based contrast agent. Pharmacokinetic modeling was applied to contrast concentration time-curves to estimate BBB leakage rate in each voxel. Subsequently, leakage rate was calculated in the white and gray matter, and primary (basic sensory and motor functions), secondary (association areas), and tertiary (higher-order cognition) brain regions. A difference in vulnerability to deterioration was expected between these regions, with especially tertiary regions being affected by age. Higher BBB leakage rate was significantly associated with older age in the white and gray matter, and also in tertiary, but not in primary or secondary brain regions. Even in healthy individuals, BBB disruption was stronger in older persons, which suggests BBB disruption is a normal physiologically aging phenomenon. Age-related increase in BBB disruption occurred especially in brain regions most vulnerable to age-related deterioration, which may indicate that BBB disruption is an underlying mechanism of normal age-related decline. Netherlands Trial Register number: NL6358, date of registration: 2017-03-24.

Age-related decline of de novo T cell responsiveness as a cause of COVID-19 severity - Francesco Nicoli; Maria Teresa Solis-Soto; Deepak Paudel; Peggy Marconi; Riccardo Gavioli; Victor Appay; Antonella Caputo (GeroScience, 2020)

Composition of Caenorhabditis elegans extracellular vesicles suggests roles in metabolism, immunity, and aging - Joshua C. Russell; Taek-Kyun Kim; Ayush Noori; Gennifer E. Merrihew; Julia E. Robbins; Alexandra Golubeva; Kai Wang; Michael J. MacCoss; Matt Kaeberlein (GeroScience, 2020)

Elderly at time of COronaVIrus disease 2019 (COVID-19): possible role of immunosenescence and malnutrition - Leonardo Bencivenga; Giuseppe Rengo; Gilda Varricchi (GeroScience, 2020)

Inducible aging in Hydra oligactis implicates sexual reproduction, loss of stem cells, and genome maintenance as major pathways - Shixiang Sun; Ryan R. White; Kathleen E. Fischer; Zhengdong Zhang; Steven N. Austad; Jan Vijg (GeroScience, 2020)

Gene expression and regulatory factors of the mechanistic target of rapamycin (mTOR) complex 1 predict mammalian longevity - Natalia Mota-Martorell; Mariona Jove; Irene Pradas; Rebeca Berdún; Isabel Sanchez; Alba Naudi; Eloi Gari; Gustavo Barja; Reinald Pamplona (GeroScience, 2020)

Poor mitochondrial health and systemic inflammation? Test of a classic hypothesis in the Baltimore Longitudinal Study of Aging - Marta Zampino; Nicholas A. Brennan; Pei-Lun Kuo; Richard G. Spencer; Kenneth W. Fishbein; Eleanor M. Simonsick; Luigi Ferrucci (GeroScience, 2020)

Severe COVID-19 and aging: are monocytes the key? - Brandt D. Pence (GeroScience, 2020)
The ongoing pandemic severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes a disproportionate number of severe cases and deaths in older adults. Severe SARS-CoV-2-associated disease (coronavirus disease 2019 (COVID-19)) was declared a pandemic by the World Health Organization in March 2020 and is characterized by cytokine storm, acute respiratory distress syndrome, and in some cases by systemic inflammation–related pathology. Currently, our knowledge of the determinants of severe COVID-19 is primarily observational. Here, I review emerging evidence to argue that monocytes, a circulating innate immune cell, are principal players in cytokine storm and associated pathologies in COVID-19. I also describe changes in monocyte function and phenotype that are characteristic of both aging and severe COVID-19, which suggests a potential mechanism underlying increased morbidity and mortality due to SARS-CoV-2 infection in older adults. The innate immune system is therefore a potentially important target for therapeutic treatment of COVID-19, but experimental studies are needed, and SARS-CoV-2 presents unique challenges for pre-clinical and mechanistic studies in vivo. The immediate establishment of colonies of SARS-CoV-2-susceptible animal models for aging studies, as well as strong collaborative efforts in the geroscience community, will be required in order to develop the therapies needed to combat severe COVID-19 in older adult populations.

The effect of social distance measures on COVID-19 epidemics in Europe: an interrupted time series analysis - Zoltán Vokó; János György Pitter (GeroScience, 2020)
Following the introduction of unprecedented “stay-at-home” national policies, the COVID-19 pandemic recently started declining in Europe. Our research aims were to characterize the changepoint in the flow of the COVID-19 epidemic in each European country and to evaluate the association of the level of social distancing with the observed decline in the national epidemics. Interrupted time series analyses were conducted in 28 European countries. Social distance index was calculated based on Google Community Mobility Reports. Changepoints were estimated by threshold regression, national findings were analyzed by Poisson regression, and the effect of social distancing in mixed effects Poisson regression model. Our findings identified the most probable changepoints in 28 European countries. Before changepoint, incidence of new COVID-19 cases grew by 24% per day on average. From the changepoint, this growth rate was reduced to 0.9%, 0.3% increase, and to 0.7% and 1.7% decrease by increasing social distancing quartiles. The beneficial effect of higher social distance quartiles (i.e., turning the increase into decline) was statistically significant for the fourth quartile. Notably, many countries in lower quartiles also achieved a flat epidemic curve. In these countries, other plausible COVID-19 containment measures could contribute to controlling the first wave of the disease. The association of social distance quartiles with viral spread could also be hindered by local bottlenecks in infection control. Our results allow for moderate optimism related to the gradual lifting of social distance measures in the general population, and call for specific attention to the protection of focal micro-societies enriching high-risk elderly subjects, including nursing homes and chronic care facilities.

Does SARS-CoV-2 infection cause chronic neurological complications? - Erin R. Hascup; Kevin N. Hascup (GeroScience, 2020)

COVID-19-associated cardiovascular morbidity in older adults: a position paper from the Italian Society of Cardiovascular Researches - F. Moccia; A. Gerbino; V. Lionetti; M. Miragoli; L. M. Munaron; P. Pagliaro; T. Pasqua; C. Penna; C. Rocca; M. Samaja; T. Angelone (GeroScience, 2020)

Nursing homes and the elderly regarding the COVID-19 pandemic: situation report from Hungary - Gábor Kemenesi; László Kornya; Gábor Endre Tóth; Kornélia Kurucz; Safia Zeghbib; Balázs A. Somogyi; Viktor Zöldi; Péter Urbán; Róbert Herczeg; Ferenc Jakab (GeroScience, 2020)
The global impact of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is significant in terms of public health effects and its long-term socio-economic implications. Among all social groups, the elderly is by far the most affected age group regarding morbidity and mortality. In multiple countries spanning several continents, there are an increasing number of reports referencing the novel coronavirus disease-2019 (COVID-19) spread among nursing homes. These areas are now recognized as potent hotspots regarding the pandemic, which one considers with special regard. Herein, we present currently available data of fatal COVID-19 cases throughout Hungary, along with the analysis of the co-morbidity network. We also report on viral genomic data originating from a nursing home resident. The genomic data was used for viral haplotype network analysis. We emphasize the urgent need for public health authorities to focus on nursing homes and residential service units worldwide, especially in the care of the elderly and infirmed. Our results further emphasize the recent statement released by the World Health Organization (WHO) regarding the vulnerability among seniors and especially the high risk of COVID-19 emergence throughout nursing and social homes.

Molecular changes in transcription and metabolic pathways underlying muscle atrophy in the CuZnSOD null mouse model of sarcopenia - Kavithalakshmi Sataranatarajan; Gavin Pharaoh; Jacob L. Brown; Rojina Ranjit; Katarzyna M. Piekarz; Kaitlyn Street; Jonathan D. Wren; Constantin Georgescu; Caroline Kinter; Michael Kinter; Willard M. Freeman; Arlan Richardson; et al. (GeroScience, 2020)

Perinatal diet influences health and survival in a mouse model of leukemia - Dushani L. Palliyaguru; Annamaria L. Rudderow; Alex M. Sossong; Kaitlyn N. Lewis; Caitlin Younts; Kevin J. Pearson; Michel Bernier; Rafael de Cabo (GeroScience, 2020)

The importance of diversity and outreach in geroscience research: Insights from the Annual Biomedical Research Conference for Minority Students - Mitchell B. Lee; Dibyadeep Datta; Cristal M. Hill; Alessandro Bitto (GeroScience, 2020)

Correction to: SARS-CoV-2 and COVID-19 in older adults: what we may expect regarding pathogenesis, immune responses, and outcomes - Janko Nikolich-Zugich; Kenneth S. Knox; Carlos Tafich Rios; Bhupinder Natt; Deepta Bhattacharya; Mindy J. Fain (GeroScience, 2020)

A short life on the farm: aging and longevity in agricultural, large-bodied mammals - Jessica M. Hoffman; Teresa G. Valencak (GeroScience, 2020)

Mitochondrial adaptations in liver and skeletal muscle to pro-longevity nutritional and genetic interventions: the crosstalk between calorie restriction and CYB5R3 overexpression in transgenic mice - Sandra Rodríguez-López; Sara López-Bellón; José A. González-Reyes; M. Isabel Burón; Rafael de Cabo; José M. Villalba (GeroScience, 2020)

Aging alters acetylation status in skeletal and cardiac muscles - Dongwook Yeo; Chounghun Kang; Li Li Ji (GeroScience, 2020)

Long-term treatment with spermidine increases health span of middle-aged Sprague-Dawley male rats - Madalina Filfan; Andrei Olaru; Ion Udristoiu; Claudiu Margaritescu; Eugen Petcu; Dirk M Hermann; Aurel Popa-Wagner (GeroScience, 2020)

Heterochronic parabiosis regulates the extent of cellular senescence in multiple tissues - Matthew J. Yousefzadeh; John E. Wilkinson; Brian Hughes; Namrata Gadela; Warren C. Ladiges; Nam Vo; Laura J. Niedernhofer; Derek M. Huffman; Paul D. Robbins (GeroScience, 2020)

Developmental exposure to Δ9-tetrahydrocannabinol (THC) causes biphasic effects on longevity, inflammation, and reproduction in aged zebrafish (Danio rerio) - Zacharias Pandelides; Cammi Thornton; Kayla G. Lovitt; Anika S. Faruque; Alyssa P. Whitehead; Kristine L. Willett; Nicole M. Ashpole (GeroScience, 2020)

DNA methylation and histone acetylation changes to cytochrome P450 2E1 regulation in normal aging and impact on rates of drug metabolism in the liver - Mohamad M. Kronfol; Fay M. Jahr; Mikhail G. Dozmorov; Palak S. Phansalkar; Lin Y. Xie; Karolina A. Aberg; MaryPeace McRae; Elvin T. Price; Patricia W. Slattum; Philip M. Gerk; Joseph L. McClay (GeroScience, 2020)

Drug synergy as a strategy for compression of morbidity in a Caenorhabditis elegans model of Alzheimer’s disease - Emelyne Teo; Sheng Fong; Nicholas Tolwinski; Jan Gruber (GeroScience, 2020)

n-3 polyunsaturated fatty acids as modulators of thermogenesis in Ames dwarf mice - Nadine Lenzhofer; Sarah A. Ohrnberger; Teresa G. Valencak (GeroScience, 2020)

Increased nuclear permeability is a driver for age-related motoneuron loss - Ashley Gillon; Charlotte Steel; Jon Cornwall; Philip Sheard (GeroScience, 2020)

Age-related changes in the cartilage of the temporomandibular joint - Po-Jung Chen; Eliane Hermes Dutra; Shivam Mehta; Mara H. O’Brien; Sumit Yadav (GeroScience, 2020)

Tryptophan metabolism is differently regulated between large and small dogs - Jessica M. Hoffman; J. Veronika Kiklevich; Marika Austad; ViLinh Tran; Dean P. Jones; Angela Royal; Carolyn Henry; Steven N. Austad (GeroScience, 2020)
Companion dogs have recently been promoted as an animal model for the study of aging due to their similar disease profile to humans, the sophistication of health assessment and disease diagnosis, and the shared environments with their owners. In addition, dogs show an interesting life history trait pattern where smaller individuals are up to two-fold longer lived than their larger counterparts. While some of the mechanisms underlying this size and longevity trade-off are strongly suspected (i.e., growth hormone/IGF-I), there are likely a number of undiscovered mechanisms as well. Accordingly, we have completed a large-scale global metabolomic profiling of dogs encompassing a range of sizes and ages from three cities across the USA. We found a surprisingly strong location signal in the metabolome, stronger in fact than any signal related to age, breed, or sex. However, after controlling for the effects of location, tryptophan metabolism emerged as significantly associated with weight of the dogs, with small dogs having significantly higher levels of tryptophan pathway metabolites. Overall, our results point toward novel, testable hypotheses about the underlying physiological mechanisms that influence size and longevity in the companion dog and suggest that dogs may be useful in sorting out the complexities of the tryptophan metabolic network.

A pro longevity role for cellular senescence - Amany Attaallah; Monia Lenzi; Silvia Marchionni; Giacomo Bincoletto; Veronica Cocchi; Eleonora Croco; Patrizia Hrelia; Silvana Hrelia; Christian Sell; Antonello Lorenzini (GeroScience, 2020)

What is the rate-limiting step towards aging? Chemical reaction kinetics might reconcile contradictory observations in experimental aging research - Sascha Kunath; Bernd Moosmann (GeroScience, 2020)

Regulation of senescence traits by MAPKs - Carlos Anerillas; Kotb Abdelmohsen; Myriam Gorospe (GeroScience, 2020)

SARS-CoV-2 and COVID-19 in older adults: what we may expect regarding pathogenesis, immune responses, and outcomes - Janko Nikolich-Zugich; Kenneth S. Knox; Carlos Tafich Rios; Bhupinder Natt; Deepta Bhattacharya; Mindy J. Fain (GeroScience, 2020)

Single-cell RNA sequencing identifies senescent cerebromicrovascular endothelial cells in the aged mouse brain - Tamas Kiss; Ádám Nyúl-Tóth; Priya Balasubramanian; Stefano Tarantini; Chetan Ahire; Jordan DelFavero; Andriy Yabluchanskiy; Tamas Csipo; Eszter Farkas; Graham Wiley; Lori Garman; Anna Csiszar; et al. (GeroScience, 2020)

Commentary: rapamycin for the aging skin - Christian Sell (GeroScience, 2020)

Developmental exposure to cannabidiol (CBD) alters longevity and health span of zebrafish (Danio rerio) - Zacharias Pandelides; Cammi Thornton; Anika S. Faruque; Alyssa P. Whitehead; Kristine L. Willett; Nicole M. Ashpole (GeroScience, 2020)

A novel tissue culture model for evaluating the effect of aging on stem cell fate in adult microvascular networks - Mohammad S. Azimi; Jessica M. Motherwell; Maria Dutreil; Ryan L. Fishel; Matthew Nice; Nicholas A. Hodges; Bruce A. Bunnell; Adam Katz; Walter L. Murfee (GeroScience, 2020)

Circulating anti-geronic factors from heterochonic parabionts promote vascular rejuvenation in aged mice: transcriptional footprint of mitochondrial protection, attenuation of oxidative stress, and rescue of endothelial function by young blood - Tamas Kiss; Stefano Tarantini; Tamas Csipo; Priya Balasubramanian; Ádám Nyúl-Tóth; Andriy Yabluchanskiy; Jonathan D. Wren; Lori Garman; Derek M. Huffman; Anna Csiszar; Zoltan Ungvari (GeroScience, 2020)

Human brain networks: a graph theoretical analysis of cortical connectivity normative database from EEG data in healthy elderly subjects - Fabrizio Vecchio; Francesca Miraglia; Elda Judica; Maria Cotelli; Francesca Alù; Paolo Maria Rossini (GeroScience, 2020)

Accelerated cerebral vascular injury in diabetes is associated with vascular smooth muscle cell dysfunction - Ya Guo; Shaoxun Wang; Yedan Liu; Letao Fan; George W. Booz; Richard J. Roman; Zongbo Chen; Fan Fan (GeroScience, 2020)

Strain-specificity in the hydrogen sulphide signalling network following dietary restriction in recombinant inbred mice - Stephen E. Wilkie; Lorna Mulvey; William A. Sands; Diana E. Marcu; Roderick N. Carter; Nicholas M. Morton; Christopher Hine; James R. Mitchell; Colin Selman (GeroScience, 2020)
Modulation of the ageing process by dietary restriction (DR) across multiple taxa is well established. While the exact mechanism through which DR acts remains elusive, the gasotransmitter hydrogen sulphide (H 2 S) may play an important role. We employed a comparative-type approach using females from three ILSXISS recombinant inbred mouse strains previously reported to show differential lifespan responses following 40% DR. Following long-term (10 months) 40% DR, strain TejJ89—reported to show lifespan extension under DR—exhibited elevated hepatic H 2 S production relative to its strain-specific ad libitum (AL) control. Strain TejJ48 (no reported lifespan effect following 40% DR) exhibited significantly reduced hepatic H 2 S production, while H 2 S production was unaffected by DR in strain TejJ114 (shortened lifespan reported following 40% DR). These differences in H 2 S production were reflected in highly divergent gene and protein expression profiles of the major H 2 S production and disposal enzymes across strains. Increased hepatic H 2 S production in TejJ89 mice was associated with elevation of the mitochondrial H 2 S-producing enzyme 3-mercaptopyruvate sulfurtransferase (MPST). Our findings further support the potential role of H 2 S in DR-induced longevity and indicate the presence of genotypic-specificity in the production and disposal of hepatic H 2 S in response to 40% DR in mice.

Advances in cytomegalovirus (CMV) biology and its relationship to health, diseases, and aging - Janko Nikolich-Žugich; Luka Čicin-Šain; Donna Collins-McMillen; Sarah Jackson; Annette Oxenius; John Sinclair; Christopher Snyder; Mark Wills; Niels Lemmermann (GeroScience, 2020)

Effects of nutraceutical intervention on serum proteins in aged rats - Samantha M. Portis; Dale Chaput; Beau Burroughs; Charles Hudson; Paul R. Sanberg; Paula C. Bickford (GeroScience, 2020)
Aging is associated with many pathophysiological changes that could lead to the onset of degenerative disease. Some of the physiological changes that occur with aging include increased inflammation and decreased stem cell proliferation, leading to decreased capacity for tissue regeneration and loss of function. In previous studies, we and others have found nutraceutical intervention to ameliorate some of the deleterious effects associated with aging. In particular, we have previously shown that NT-020, a supplement composed of a proprietary blend of blueberries, green tea, vitamin D3, and carnosine, is able to rescue age-related cognitive deficits, impaired neurogenesis, and inflammation in rats. We have also previously demonstrated that stem cells cultured with old serum showed decreased proliferation; however, when stem cells were cultured in serum from old rats given a diet supplemented with NT-020, proliferation did not differ from that of cells cultured with serum from young rats. While it is clear that NT-020 is exerting a therapeutic, anti-aging effect, the mechanisms of action were yet to be fully elucidated.To that end, in the present study, we conducted a bioinformatics experiment to examine the rat proteome of serum from young and old control rats and young and old rats given a diet supplemented with NT-020. Serum from old rats showed an increase in some inflammatory and pro-aging factors while serum from old rats given a diet supplemented with NT-020 showed an increase in some anti-aging factors, most notably proteins associated with the complement system and autophagy. A number of immune functions that increase with age were shown to be downregulated with NT-020 treatment.

Molecular changes associated with spinal cord aging - Katarzyna M. Piekarz; Shylesh Bhaskaran; Kavithalakshmi Sataranatarajan; Kaitlyn Street; Pavithra Premkumar; Debra Saunders; Michelle Zalles; Rafal Gulej; Shadi Khademi; Jaime Laurin; Rick Peelor; Benjamin F. Miller; et al. (GeroScience, 2020)

CD82-TRPM7-Numb signaling mediates age-related cognitive impairment - Yin Zhao; Tamas Kiss; Jordan DelFavero; Lu Li; Xing Li; Lu Zheng; Jie Wang; Chao Jiang; Jing Shi; Zoltan Ungvari; Anna Csiszar; Xin A. Zhang (GeroScience, 2020)

Nicotinamide mononucleotide (NMN) supplementation promotes neurovascular rejuvenation in aged mice: transcriptional footprint of SIRT1 activation, mitochondrial protection, anti-inflammatory, and anti-apoptotic effects - Tamas Kiss; Ádám Nyúl-Tóth; Priya Balasubramanian; Stefano Tarantini; Chetan Ahire; Andriy Yabluchanskiy; Tamas Csipo; Eszter Farkas; Jonathan D. Wren; Lori Garman; Anna Csiszar; Zoltan Ungvari (GeroScience, 2020)

Pharmacotherapy to gene editing: potential therapeutic approaches for Hutchinson–Gilford progeria syndrome - Saurabh Saxena; Sanjeev Kumar (GeroScience, 2020)

Neurovascular unit dysregulation, white matter disease, and executive dysfunction: the shared triad of vascular cognitive impairment and Alzheimer disease - Alexander Levit; Vladimir Hachinski; Shawn N. Whitehead (GeroScience, 2020)

Sex-specific muscle and metabolic biomarkers associated with gait speed and cognitive transitions in older adults: a 9-year follow-up - D. L. Waters; L. Vlietstra; C. Qualls; J. E. Morley; B. Vellas (GeroScience, 2020)

Age-related murine hippocampal CA1 laminae oxidative stress measured in vivo by QUEnch-assiSTed (QUEST) MRI: impact of isoflurane anesthesia - Bruce A. Berkowitz; Robert H. Podolsky; Karen Lins Childers; Alexander Gow; Brandy L. Schneider; Scott C. Lloyd; Kelly E. Bosse; Alana C. Conti; Robin Roberts; Ali M. Berri; Emma Graffice; Kenan Sinan; et al. (GeroScience, 2020)
Age-related impairments in spatial learning and memory often precede non-familial neurodegenerative disease. Ex vivo studies suggest that physiologic age-related oxidative stress in hippocampus area CA1 may contribute to prodromal spatial disorientation and to morbidity. Yet, conventional blood or cerebrospinal fluid assays appear insufficient for early detection or management of oxidative stress within CA1 sub-regions in vivo. Here, we address this biomarker problem using a non-invasive MRI index of CA1 laminae oxidative stress based on reduction in R1 (= 1/T1) after anti-oxidant administration. An R1 reduction reflects quenching of continuous and excessive production of endogenous paramagnetic free radicals. Careful motion-correction image acquisition, and avoiding repeated exposure to isoflurane, facilitates detection of hippocampus CA1 laminae oxidative stress with QUEnch-assiSTed (QUEST) MRI. Intriguingly, age- and isoflurane-related oxidative stress is localized to the stratum lacunosum of the CA1 region. Our data raise the possibility of using QUEST MRI and FDA-approved anti-oxidants to remediate spatial disorientation and later neurodegeneration with age in animals and humans.

One-year Mediterranean diet promotes epigenetic rejuvenation with country- and sex-specific effects: a pilot study from the NU-AGE project - Noémie Gensous; Paolo Garagnani; Aurelia Santoro; Cristina Giuliani; Rita Ostan; Cristina Fabbri; Maddalena Milazzo; Davide Gentilini; Anna Maria di Blasio; Barbara Pietruszka; Dawid Madej; Agata Bialecka-Debek; et al. (GeroScience, 2020)
Mediterranean diet has been proposed to promote healthy aging, but its effects on aging biomarkers have been poorly investigated. We evaluated the impact of a 1-year Mediterranean-like diet in a pilot study including 120 elderly healthy subjects from the NU-AGE study (60 Italians, 60 Poles) by measuring the changes in their epigenetic age, assessed by Horvath’s clock. We observed a trend towards epigenetic rejuvenation of participants after nutritional intervention. The effect was statistically significant in the group of Polish females and in subjects who were epigenetically older at baseline. A genome-wide association study of epigenetic age changes after the intervention did not return significant (adjusted p value < 0.05) loci. However, we identified small-effect alleles (nominal p value < 10–4), mapping in genes enriched in pathways related to energy metabolism, regulation of cell cycle, and of immune functions. Together, these findings suggest that Mediterranean diet can promote epigenetic rejuvenation but with country-, sex-, and individual-specific effects, thus highlighting the need for a personalized approach to nutritional interventions.

Correction to: Age- and sex-specific effects in paravertebral surface electromyographic back extensor muscle fatigue in chronic low back pain - Gerold Ebenbichler; Richard Habenicht; Sara Ziegelbecker; Josef Kollmitzer; Patrick Mair; Thomas Kienbacher (GeroScience, 2020)

Blockade of the NLRP3 inflammasome improves metabolic health and lifespan in obese mice - Diego Cañadas-Lozano; Fabiola Marín-Aguilar; Beatriz Castejón-Vega; Bernhard Ryffel; José M. Navarro-Pando; Jesús Ruiz-Cabello; Elísabet Alcocer-Gómez; Pedro Bullón; Mario D. Cordero (GeroScience, 2020)

Microglial autophagy is impaired by prolonged exposure to β-amyloid peptides: evidence from experimental models and Alzheimer’s disease patients - Carlos Pomilio; Roxana M. Gorojod; Miguel Riudavets; Angeles Vinuesa; Jessica Presa; Amal Gregosa; Melisa Bentivegna; Agustina Alaimo; Soledad Porte Alcon; Gustavo Sevlever; Monica L. Kotler; Juan Beauquis; et al. (GeroScience, 2020)

Short-term time-restricted feeding is safe and feasible in non-obese healthy midlife and older adults - Christopher R. Martens; Matthew J. Rossman; Melissa R. Mazzo; Lindsey R. Jankowski; Erzsebet E. Nagy; Blair A. Denman; James J. Richey; Sarah A. Johnson; Brian P. Ziemba; Yang Wang; Courtney M. Peterson; Michel Chonchol; et al. (GeroScience, 2020)

Loss of vacuolar acidity results in iron-sulfur cluster defects and divergent homeostatic responses during aging in Saccharomyces cerevisiae - Kenneth L. Chen; Toby N. Ven; Matthew M. Crane; Matthew L. C. Brunner; Adrian K. Pun; Kathleen L. Helget; Katherine Brower; Dexter E. Chen; Ha Doan; Justin D. Dillard-Telm; Ellen Huynh; Yen-Chi Feng; et al. (GeroScience, 2020)

Mitochondrial base excision repair positively correlates with longevity in the liver and heart of mammals - Ricardo Gredilla; Inés Sánchez-Román; Alexia Gómez; Mónica López-Torres; Gustavo Barja (GeroScience, 2020)

Pharmacological or genetic depletion of senescent astrocytes prevents whole brain irradiation–induced impairment of neurovascular coupling responses protecting cognitive function in mice - Andriy Yabluchanskiy; Stefano Tarantini; Priya Balasubramanian; Tamas Kiss; Tamas Csipo; Gábor A. Fülöp; Agnes Lipecz; Chetan Ahire; Jordan DelFavero; Adam Nyul-Toth; William E. Sonntag; Michal L. Schwartzman; et al. (GeroScience, 2020)

NIA workshop on senescence in brain aging and Alzheimer’s disease and its related dementias - Amanda M. DiBattista; Felipe Sierra; Eliezer Masliah (GeroScience, 2020)

Negligible senescence in naked mole rats may be a consequence of well-maintained splicing regulation - B. P. Lee; M. Smith; R. Buffenstein; L. W. Harries (GeroScience, 2020)
Naked mole-rats (NMRs) have amongst the longest lifespans relative to body size of any known, non-volant mammalian species. They also display an enhanced stress resistance phenotype, negligible senescence and very rarely are they burdened with chronic age-related diseases. Alternative splicing (AS) dysregulation is emerging as a potential driver of senescence and ageing. We hypothesised that the expression of splicing factors, important regulators of patterns of AS, may differ in NMRs when compared to other species with relatively shorter lifespans. We designed assays specific to NMR splicing regulatory factors and also to a panel of pre-selected brain-expressed genes known to demonstrate senescence-related alterations in AS in other species, and measured age-related changes in the transcript expression levels of these using embryonic and neonatal developmental stages through to extreme old age in NMR brain samples. We also compared splicing factor expression in both young mouse and NMR spleen and brain samples. Both NMR tissues showed approximately double the expression levels observed in tissues from similarly sized mice. Furthermore, contrary to observations in other species, following a brief period of labile expression in early life stages, adult NMR splicing factors and patterns of AS for functionally relevant brain genes remained remarkably stable for at least two decades. These findings are consistent with a model whereby the conservation of splicing regulation and stable patterns of AS may contribute to better molecular stress responses and the avoidance of senescence in NMRs, contributing to their exceptional lifespan and prolonged healthspan.

Raman fingerprints as promising markers of cellular senescence and aging - Lisa Liendl; Johannes Grillari; Markus Schosserer (GeroScience, 2020)

Nanodelivery of phytobioactive compounds for treating aging-associated disorders - Oleh Lushchak; Olha Strilbytska; Alexander Koliada; Alina Zayachkivska; Nadia Burdyliuk; Ihor Yurkevych; Kenneth B. Storey; Alexander Vaiserman (GeroScience, 2020)

Metformin and cognition from the perspectives of sex, age, and disease - Kiran Chaudhari; Conner D. Reynolds; Shao-Hua Yang (GeroScience, 2020)

Correction to: Inflammaging phenotype in rhesus macaques is associated with a decline in epithelial barrier-protective functions and increased pro-inflammatory function in CD161-expressing cells - Edith M. Walker; Nadia Slisarenko; Giovanni L. Gerrets; Patricia J. Kissinger; Elizabeth S. Didier; Marcelo J. Kuroda; Ronald S. Veazey; S. Michal Jazwinski; Namita Rout (GeroScience, 2020)

Magnetic resonance elastography (MRE) shows significant reduction of thigh muscle stiffness in healthy older adults - Paul Kennedy; Eric Barnhill; Calum Gray; Colin Brown; Edwin J.R. van Beek; Neil Roberts; Carolyn Anne Greig (GeroScience, 2020)
Determining the effect of ageing on thigh muscle stiffness using magnetic resonance elastography (MRE) and investigate whether fat fraction and muscle cross-sectional area (CSA) are related to stiffness. Six healthy older adults in their eighth and ninth decade and eight healthy young men were recruited and underwent a 3 T MRI protocol including MRE and Dixon fat fraction imaging. Muscle stiffness, fat fraction and muscle CSA were calculated in ROIs corresponding to the four quadriceps muscles (i.e. vastus lateralis (VL), vastus medialis (VM), vastus intermedius (VI), rectus femoris (RF)), combined quadriceps, combined hamstrings and adductors and whole thigh. Muscle stiffness was significantly reduced ( p < 0.05) in the older group in all measured ROIs except the VI ( p = 0.573) and RF ( p = 0.081). Similarly, mean fat fraction was significantly increased ( p < 0.05) in the older group over all ROIs with the exception of the VI ( p = 0.059) and VL muscle groups ( p = 0.142). Muscle CSA was significantly reduced in older participants in the VM ( p = 0.003) and the combined quadriceps ( p = 0.001), hamstrings and adductors ( p = 0.008) and whole thigh ( p = 0.003). Over the whole thigh, stiffness was significantly negatively correlated with fat fraction ( r = − 0.560, p = 0.037) and positively correlated with CSA ( r = 0.749, p = 0.002). Stepwise regression analysis revealed that age was the most significant predictor of muscle stiffness ( p = 0.001). These results suggest that muscle stiffness is significantly decreased in healthy older adults. Muscle fat fraction and muscle CSA are also significantly changed in older adults; however, age is the most significant predictor of muscle stiffness.

In vivo assessment of mitochondrial capacity using NIRS in locomotor muscles of young and elderly males with similar physical activity levels - Bart Lagerwaard; Arie G. Nieuwenhuizen; Vincent C. J. de Boer; Jaap Keijer (GeroScience, 2020)
Mitochondrial capacity is pivotal to skeletal muscle function and is suggested to decline with age. However, there is large heterogeneity in current data, possibly due to effect modifiers such as physical activity, sex and muscle group. Yet, few studies have compared multiple muscle groups in different age groups with comparable physical activity levels. Here, we newly used near-infrared spectroscopy (NIRS) to characterise mitochondrial capacity in three different locomotor muscles in young (19–25 year) and older (65–71 year), healthy males with similar physical activity levels. Mitochondrial capacity and reperfusion after arterial occlusion was measured in the vastus lateralis (VL), the gastrocnemius (GA) and the tibialis anterior (TA). Physical activity was verified using accelerometry and was not different between the age groups (404.3 ± 214.9 vs 494.9 ± 187.0 activity kcal per day, p = 0.16). Mitochondrial capacity was significantly lower in older males in the GA and VL, but not in the TA ( p = 0.048, p = 0.036 and p = 0.64, respectively). Reperfusion rate was not significantly different for the GA ( p = 0.55), but was significantly faster in the TA and VL in the young group compared to the older group ( p = 0.0094 and p = 0.039, respectively). In conclusion, we identified distinct modes of mitochondrial ageing in different locomotor muscles in a young and older population with similar physical activity patterns. Furthermore, we show that NIRS is suitable for relatively easy application in ageing research and can reveal novel insights into mitochondrial functioning with age.

Lumbar spinal cord microglia exhibited increased activation in aging dogs compared with young adult dogs - Christine M. Toedebusch; Virginia B. Garcia; John C. Snyder; Maria R. Jones; David J Schulz; Gayle C. Johnson; Eric Villalón; Joan R. Coates; Michael L. Garcia (GeroScience, 2020)

Direct electrophysiological evidence that spreading depolarization-induced spreading depression is the pathophysiological correlate of the migraine aura and a review of the spreading depolarization continuum of acute neuronal mass injury - Sebastian Major; Shufan Huo; Coline L. Lemale; Eberhard Siebert; Denny Milakara; Johannes Woitzik; Karen Gertz; Jens P. Dreier (GeroScience, 2020)

Lipoteichoic acid from the cell wall of a heat killed Lactobacillus paracasei D3-5 ameliorates aging-related leaky gut, inflammation and improves physical and cognitive functions: from C. elegans to mice - Shaohua Wang; Shokouh Ahmadi; Ravinder Nagpal; Shalini Jain; Sidharth P. Mishra; Kylie Kavanagh; Xuewei Zhu; Zhan Wang; Donald A. McClain; Stephen B. Kritchevsky; Dalane W. Kitzman; Hariom Yadav (GeroScience, 2020)

Proceedings from the Albert Charitable Trust Inaugural Workshop on white matter and cognition in aging - Farzaneh A. Sorond; Shawn Whitehead; Ken Arai; Douglas Arnold; S. Thomas Carmichael; Charles De Carli; Marco Duering; Myriam Fornage; Rafael E. Flores-Obando; Jonathan Graff-Radford; Edith Hamel; David C. Hess; et al. (GeroScience, 2020)

circRNAs expressed in human peripheral blood are associated with human aging phenotypes, cellular senescence and mouse lifespan - Shahnaz Haque; Ryan M. Ames; Karen Moore; Luke C. Pilling; Luanne L. Peters; Stefania Bandinelli; Luigi Ferrucci; Lorna W. Harries (GeroScience, 2020)
Circular RNAs (circRNAs) are an emerging class of non-coding RNA molecules that are thought to regulate gene expression and human disease. Despite the observation that circRNAs are known to accumulate in older organisms and have been reported in cellular senescence, their role in aging remains relatively unexplored. Here, we have assessed circRNA expression in aging human blood and followed up age-associated circRNA in relation to human aging phenotypes, mammalian longevity as measured by mouse median strain lifespan and cellular senescence in four different primary human cell types. We found that circRNAs circDEF6 , c ircEP300 , circFOXO3 and circFNDC3B demonstrate associations with parental longevity or hand grip strength in 306 subjects from the InCHIANTI study of aging, and furthermore, circFOXO3 and circEP300 also demonstrate differential expression in one or more human senescent cell types. Finally, four circRNAs tested showed evidence of conservation in mouse. Expression levels of one of these, circPlekhm1 , was nominally associated with lifespan. These data suggest that circRNA may represent a novel class of regulatory RNA involved in the determination of aging phenotypes, which may show future promise as both biomarkers and future therapeutic targets for age-related disease.

The smell of longevity: a combination of Volatile Organic Compounds (VOCs) can discriminate centenarians and their offspring from age-matched subjects and young controls - Maria Conte; Giuseppe Conte; Morena Martucci; Daniela Monti; Laura Casarosa; Andrea Serra; Marcello Mele; Claudio Franceschi; Stefano Salvioli (GeroScience, 2020)

The role of exercise in the reversal of IGF-1 deficiencies in microvascular rarefaction and hypertension - Amani M. Norling; Adam T. Gerstenecker; Thomas W. Buford; Bilal Khan; Suzanne Oparil; Ronald M. Lazar (GeroScience, 2020)

Ellagic acid prolongs the lifespan of Drosophila melanogaster - Priyanka Kharat; Priyanka Sarkar; S. Mouliganesh; Vaibhav Tiwary; V.B. Ramya Priya; N. Yamini Sree; H. Vinu Annapoorna; Diganta K. Saikia; Kaustav Mahanta; Kavitha Thirumurugan (GeroScience, 2020)

Older adults demonstrate interlimb transfer of reactive gait adaptations to repeated unpredictable gait perturbations - Christopher McCrum; Kiros Karamanidis; Lotte Grevendonk; Wiebren Zijlstra; Kenneth Meijer (GeroScience, 2020)
The ability to rapidly adjust gait to cope with unexpected mechanical perturbations declines with ageing. Previous studies, however, have not ensured that gait stability pre-perturbation was equivalent across participants or age groups which may have influenced the outcomes. In this study, we investigate if age-related differences in stability following gait perturbations remain when all participants walk with equivalent stability. We also examine if interlimb transfer of gait adaptations are observed in healthy older adults, by examining if adaptation to repeated perturbations of one leg can benefit stability recovery when the other leg is perturbed. During walking at their stability-normalised walking speeds (young: 1.32 ± 0.07 m/s; older: 1.31 ± 0.13 m/s; normalised to an average margin of stability of 0.05 m), 30 young and 28 older healthy adults experienced ten unpredictable treadmill belt accelerations (the first and last applied to the right leg, the others to the left leg). Using kinematic data, we assessed the margins of stability during unperturbed walking and the first eight post-perturbation recovery steps. Older adults required three more steps to recover during the first perturbation to each leg than the young adults. Yet, after repeated perturbations of the left leg, older adults required only one more step to recover. Interestingly, for the untrained right leg, the older adults could regain stability with three fewer steps, indicating interlimb transfer of the improvements. Age differences in reactive gait stability remain even when participants’ walk with equivalent stability. Furthermore, we show that healthy older adults can transfer improvements in balance recovery made during repeated perturbations to one limb to their recovery following a perturbation to the untrained limb.

Correction to: Genetic conversion of proliferative astroglia into neurons after cerebral ischemia: a new therapeutic tool for the aged brain? - Aurel Popa-Wagner; Dirk M. Hermann; Andrei Gresita (GeroScience, 2020)

Acclimation to a thermoneutral environment abolishes age-associated alterations in heart rate and heart rate variability in conscious, unrestrained mice - Jessie E. Axsom; Alay P. Nanavati; Carolyn A. Rutishauser; Janet E. Bonin; Jack M. Moen; Edward G. Lakatta (GeroScience, 2020)
Mice are among the most widely used translational models of cardiovascular aging and offer a method to quickly assess lifespan changes in a controlled environment. The standard laboratory temperature (20–22 °C), however, imposes a cold stress on mice that causes an increase in sympathetic nervous system–mediated activation of brown adipose tissue (BAT) to maintain a core body temperature of 36–37 °C. Thus, while physiologic data obtained recapitulate human physiology to a certain degree, interpretations of previous research in mice may have been contaminated by a cold stress, due to housing mice below their thermoneutral zone (30 °C). The purpose of this investigation was to examine how chronic sympathetic stimulation evoked by acclimation to 20 °C might obscure interpretation of changes in autonomic modulation of heart rate (HR) and heart rate variability (HRV) that accompany advancing age. HR and HRV before and after administration of a dual-autonomic blockade were measured via in-vivo ECG in young (3 months) and aged (30 months) male C57BL/6 telemetry-implanted mice following temperature acclimation for 3 days at 30 °C or 20 °C. Mean basal and intrinsic HR of both young and aged mice became markedly reduced at 30 °C compared to 20 °C. In both age groups, HRV parameters in time, frequency, and non-linear domains displayed increased variability at 30 °C compared to 20 °C under basal conditions. Importantly, age-associated declines in HRV observed at 20 °C were ameliorated when mice were studied at their thermoneutral ambient temperature of 30 °C. Thus, an accurate understanding of autonomic modulation of cardiovascular functions in mice of advanced age requires that they are housed in a metabolically neutral environment.

Age- and sex-specific effects in paravertebral surface electromyographic back extensor muscle fatigue in chronic low back pain - Gerold Ebenbichler; Richard Habenicht; Sara Ziegelbecker; Josef Kollmitzer; Patrick Mair; Thomas Kienbacher (GeroScience, 2020)
The impact of aging on the back muscles is not well understood, yet may hold clues to both normal aging and chronic low back pain (cLBP). This study sought to investigate whether the median frequency (MF) surface electromyographic (SEMG) back muscle fatigue method—a proxy for glycolytic muscle metabolism—would be able to detect age- and sex-specific differences in neuromuscular and muscle metabolic functions in individuals with cLBP in a reliable way, and whether it would be as sensitive as when used on healthy individuals. With participants seated on a dynamometer (20° trunk anteflexion), paraspinal SEMG activity was recorded bilaterally from the multifidus (L5), longissimus (L2), and iliolumbalis (L1) muscles during isometric, sustained back extensions loaded at 80% of maximum from 117 younger (58 females) and 112 older (56 female) cLBP individuals. Tests were repeated after 1–2 days and 6 weeks. Median frequency, the SEMG variable indicating neuromuscular fatigue, was analyzed. Maximum back extensor strength was comparable between younger and older participants. Significantly less MF-SEMG back muscle fatigue was observed in older as compared to younger, and in older female as compared to older male cLBP individuals. Relative reliability was excellent, but absolute reliability appeared large for this SEMG-fatigue measure. Findings suggest that cLBP likely does not mask the age-specific diagnostic potential of the MF-SEMG back extensor fatigue method. Thus, this method possesses a great potential to be further developed into a valuable biomarker capable of detecting back muscle function at risk of sarcopenia at very early stages.

Astrocyte senescence contributes to cognitive decline - Tamas Csipo; Agnes Lipecz; Nicole M. Ashpole; Priya Balasubramanian; Stefano Tarantini (GeroScience, 2020)

Aging induced by D-galactose aggravates cardiac dysfunction via exacerbating mitochondrial dysfunction in obese insulin-resistant rats - Cherry Bo-Htay; Thazin Shwe; Louis Higgins; Siripong Palee; Krekwit Shinlapawittayatorn; Siriporn C Chattipakorn; Nipon Chattipakorn (GeroScience, 2020)

Serum beta-secretase 1 (BACE1) activity as candidate biomarker for late-onset Alzheimer’s disease - Carlo Cervellati; Alessandro Trentini; Valentina Rosta; Angelina Passaro; Cristina Bosi; Juana Maria Sanz; Stefania Bonazzi; Salvatore Pacifico; Davide Seripa; Giuseppe Valacchi; Remo Guerini; Giovanni Zuliani (GeroScience, 2020)

Methionine restriction delays aging-related urogenital diseases in male Fischer 344 rats - Despina Komninou; Virginia L. Malloy; Jay A. Zimmerman; Raghu Sinha; John P. Richie (GeroScience, 2020)

Extracellular vesicles from mesenchymal stem cells reduce microglial-mediated neuroinflammation after cortical injury in aged Rhesus monkeys - Veronica Go; Bethany G. E. Bowley; Monica A. Pessina; Zheng Gang Zhang; Michael Chopp; Seth P. Finklestein; Douglas L. Rosene; Maria Medalla; Benjamin Buller; Tara L. Moore (GeroScience, 2020)

The transfer of specific mitochondrial lipids and proteins to lipid droplets contributes to proteostasis upon stress and aging in the eukaryotic model system Saccharomyces cerevisiae - Florian Geltinger; Julia Tevini; Peter Briza; Amrito Geiser; Johannes Bischof; Klaus Richter; Thomas Felder; Mark Rinnerthaler (GeroScience, 2020)
Originally Lipid droplets (LDs) were considered as being droplets for lipid storage only. Increasing evidence, however, demonstrates that LDs fulfill a pleiotropy of additional functions. Among them is the modulation of protein as well as lipid homeostasis. Under unfavorable pro-oxidative conditions, proteins can form aggregates which may exceed the overall proteolytic capacity of the proteasome. After stress termination LDs can adjust and support the removal of these aggregates. Additionally, LDs interact with mitochondria, specifically take over certain proteins and thus prevent apoptosis. LDs, which are loaded with these harmful proteins, are subsequently eliminated via lipophagy. Recently it was demonstrated that this autophagic process is a modulator of longevity. LDs do not only eliminate potentially dangerous proteins, but they are also able to prevent lipotoxicity by storing specific lipids. In the present study we used the model organism Saccharomyces cerevisiae to compare the proteome as well as lipidome of mitochondria and LDs under different conditions: replicative aging, stress and apoptosis. In this context we found an accumulation of proteins at LDs, supporting the role of LDs in proteostasis. Additionally, the composition of main lipid classes such as phosphatidylcholines, phosphatidylethanolamines, phosphatidylinositols, phosphatidylglycerols, triacylglycerols, ceramides, phosphatidic acids and ergosterol of LDs and mitochondria changed during stress conditions and aging.

Individual evaluation of luteinizing hormone in aged C57BL/6 J female mice - Thibault Bahougne; Eleni Angelopoulou; Nathalie Jeandidier; Valérie Simonneaux (GeroScience, 2020)

Human geroprotector discovery by targeting the converging subnetworks of aging and age-related diseases - Jialiang Yang; Shouneng Peng; Bin Zhang; Sander Houten; Eric Schadt; Jun Zhu; Yousin Suh; Zhidong Tu (GeroScience, 2020)

Fusogenic liposomes effectively deliver resveratrol to the cerebral microcirculation and improve endothelium-dependent neurovascular coupling responses in aged mice - Tabea Wiedenhoeft; Stefano Tarantini; Ádám Nyúl-Tóth; Andriy Yabluchanskiy; Tamas Csipo; Priya Balasubramanian; Agnes Lipecz; Tamas Kiss; Anna Csiszar; Agnes Csiszar; Zoltan Ungvari (GeroScience, 2019)

Automated lifespan determination across Caenorhabditis strains and species reveals assay-specific effects of chemical interventions - Stephen A. Banse; Mark Lucanic; Christine A. Sedore; Anna L. Coleman-Hulbert; W. Todd Plummer; Esteban Chen; Jason L. Kish; David Hall; Brian Onken; Michael P. Presley; E. Grace Jones; Benjamin W. Blue; et al. (GeroScience, 2019)
The goal of the Caenorhabditis Intervention Testing Program is to identify robust and reproducible pro-longevity interventions that are efficacious across genetically diverse cohorts in the Caenorhabditis genus. The project design features multiple experimental replicates collected by three different laboratories. Our initial effort employed fully manual survival assays. With an interest in increasing throughput, we explored automation with flatbed scanner-based Automated Lifespan Machines (ALMs). We used ALMs to measure survivorship of 22 Caenorhabditis strains spanning three species. Additionally, we tested five chemicals that we previously found extended lifespan in manual assays. Overall, we found similar sources of variation among trials for the ALM and our previous manual assays, verifying reproducibility of outcome. Survival assessment was generally consistent between the manual and the ALM assays, although we did observe radically contrasting results for certain compound interventions. We found that particular lifespan outcome differences could be attributed to protocol elements such as enhanced light exposure of specific compounds in the ALM, underscoring that differences in technical details can influence outcomes and therefore interpretation. Overall, we demonstrate that the ALMs effectively reproduce a large, conventionally scored dataset from a diverse test set, independently validating ALMs as a robust and reproducible approach toward aging-intervention screening.

Microvascular contributions to age-related macular degeneration (AMD): from mechanisms of choriocapillaris aging to novel interventions - Agnes Lipecz; Lauren Miller; Illes Kovacs; Cecília Czakó; Tamas Csipo; Judit Baffi; Anna Csiszar; Stefano Tarantini; Zoltan Ungvari; Andriy Yabluchanskiy; Shannon Conley (GeroScience, 2019)

Topical rapamycin reduces markers of senescence and aging in human skin: an exploratory, prospective, randomized trial - Christina Lee Chung; Ibiyonu Lawrence; Melissa Hoffman; Dareen Elgindi; Kumar Nadhan; Manali Potnis; Annie Jin; Catlin Sershon; Rhonda Binnebose; Antonello Lorenzini; Christian Sell (GeroScience, 2019)
Aging is a major risk factor for the majority of human diseases, and the development of interventions to reduce the intrinsic rate of aging is expected to reduce the risk for age-related diseases including cardiovascular disease, cancer, and dementia. In the skin, aging manifests itself in photodamage and dermal atrophy, with underlying tissue reduction and impaired barrier function. To determine whether rapamycin, an FDA-approved drug targeting the mechanistic target of rapamycin (mTOR) complex, can reduce senescence and markers of aging in human skin, an exploratory, placebo-controlled, interventional trial was conducted in a clinical dermatology setting. Participants were greater than 40 years of age with evidence of age-related photoaging and dermal volume loss and no major morbidities. Thirty-six participants were enrolled in the study, and nineteen discontinued or were lost to follow-up. A significant ( P = 0.008) reduction in p16 INK4A protein levels and an increase in collagen VII protein levels ( P = 0.0077) were observed among participants at the end of the study. Clinical improvement in skin appearance was noted in multiple participants, and immunohistochemical analysis revealed improvement in histological appearance of skin tissue. Topical rapamycin reduced the expression of the p16 INK4A protein consistent with a reduction in cellular senescence. This change was accompanied by relative improvement in clinical appearance of the skin and histological markers of aging and by an increase in collagen VII, which is critical to the integrity of the basement membrane. These results indicate that rapamycin treatment is a potential anti-aging therapy with efficacy in humans. Trial registration ClinicalTrials.gov Identifier: NCT03103893.

WormBot, an open-source robotics platform for survival and behavior analysis in C. elegans - Jason N. Pitt; Nolan L. Strait; Elena M. Vayndorf; Benjamin W. Blue; Christina H. Tran; Brendon E. M. Davis; Karen Huang; Brock J. Johnson; Keong Mu Lim; Sophie Liu; Arash Nikjoo; Anuj Vaid; et al. (GeroScience, 2019)

The potential role of necroptosis in inflammaging and aging - Gordon H. Royce; Holly M. Brown-Borg; Sathyaseelan S. Deepa (GeroScience, 2019)

Inflammaging phenotype in rhesus macaques is associated with a decline in epithelial barrier-protective functions and increased pro-inflammatory function in CD161-expressing cells - Edith M. Walker; Nadia Slisarenko; Giovanni L. Gerrets; Patricia J. Kissinger; Elizabeth S. Didier; Marcelo J. Kuroda; Ronald S. Veazey; S. Michal Jazwinski; Namita Rout (GeroScience, 2019)

Polygenic risk score for disability and insights into disability-related molecular mechanisms - Alexander M. Kulminski; Chansuk Kang; Stanislav A. Kolpakov; Yury Loika; Alireza Nazarian; Anatoliy I. Yashin; Eric Stallard; Irina Culminskaya (GeroScience, 2019)

The plasma metabolome as a predictor of biological aging in humans - Lawrence C. Johnson; Keli Parker; Brandon F. Aguirre; Travis G. Nemkov; Angelo D’Alessandro; Sarah A. Johnson; Douglas R. Seals; Christopher R. Martens (GeroScience, 2019)

Age-dependent effects of caloric restriction on mTOR and ubiquitin-proteasome pathways in skeletal muscles - Chiao-Nan Chen; Yi-Hung Liao; Shiow-Chwen Tsai; LaDora V. Thompson (GeroScience, 2019)

Age-related compositional and functional changes in micro-pig gut microbiome - Mi Young Lim; Eun-Ji Song; Kyung Soo Kang; Young-Do Nam (GeroScience, 2019)

Nrf2 dysfunction and impaired cellular resilience to oxidative stressors in the aged vasculature: from increased cellular senescence to the pathogenesis of age-related vascular diseases - Zoltan Ungvari; Stefano Tarantini; Ádám Nyúl-Tóth; Tamas Kiss; Andriy Yabluchanskiy; Tamas Csipo; Priya Balasubramanian; Agnes Lipecz; Zoltan Benyo; Anna Csiszar (GeroScience, 2019)

Age-related alterations of articular cartilage in pituitary adenylate cyclase–activating polypeptide (PACAP) gene–deficient mice - Vince Szegeczki; Balázs Bauer; Adél Jüngling; Balázs Daniel Fülöp; Judit Vágó; Helga Perényi; Stefano Tarantini; Andrea Tamás; Róza Zákány; Dóra Reglődi; Tamás Juhász (GeroScience, 2019)
Pituitary adenylate cyclase activating polypeptide (PACAP) is an evolutionarly conserved neuropeptide which is produced by various neuronal and non-neuronal cells, including cartilage and bone cells. PACAP has trophic functions in tissue development, and it also plays a role in cellular and tissue aging. PACAP takes part in the regulation of chondrogenesis, which prevents insufficient cartilage formation caused by oxidative and mechanical stress. PACAP knockout (KO) mice have been shown to display early aging signs affecting several organs. In the present work, we investigated articular cartilage of knee joints in young and aged wild-type (WT) and PACAP KO mice. A significant increase in the thickness of articular cartilage was detected in aged PACAP gene–deficient mice. Amongst PACAP receptors, dominantly PAC1 receptor was expressed in WT knee joints and a remarkable decrease was found in aged PACAP KO mice. Expression of PKA-regulated transcription factors, Sox5, Sox9 and CREB, decreased both in young and aged gene deficient mice, while Sox6, collagen type II and aggrecan expressions were elevated in young but were reduced in aged PACAP KO animals. Increased expression of hyaluronan (HA) synthases and HA-binding proteins was detected parallel with an elevated presence of HA in aged PACAP KO mice. Expression of bone related collagens (I and X) was augmented in young and aged animals. These results suggest that loss of PACAP signaling results in dysregulation of cartilage matrix composition and may transform articular cartilage in a way that it becomes more prone to degenerate.

Biomarkers of leaky gut are related to inflammation and reduced physical function in older adults with cardiometabolic disease and mobility limitations - Kylie Kavanagh; Fang-Chi Hsu; Ashley T. Davis; Stephen B. Kritchevsky; W. Jack Rejeski; Sunghye Kim (GeroScience, 2019)

Differential effects of various genetic mouse models of the mechanistic target of rapamycin complex I inhibition on heart failure - Dao-Fu Dai; Yonggang Liu; Nathan Basisty; Pabalu Karunadharma; Somasish G. Dastidar; Ying Ann Chiao; Tony Chen; Richard P. Beyer; Michael T. Chin; Michael Maccoss; Albert R. La Spada; Peter S. Rabinovitch (GeroScience, 2019)

Gastro-intestinal and oral microbiome signatures associated with healthy aging - Harinder Singh; Manolito G. Torralba; Kelvin J. Moncera; Lauren DiLello; Joann Petrini; Karen E. Nelson; Rembert Pieper (GeroScience, 2019)

The enigmatic role of growth hormone in age-related diseases, cognition, and longevity - Gabriela Colon; Tatiana Saccon; Augusto Schneider; Marcelo B. Cavalcante; Derek M. Huffman; Darlene Berryman; Ed List; Yuji Ikeno; Nicolas Musi; Andrzej Bartke; John Kopchick; James L. Kirkland; et al. (GeroScience, 2019)

The effects of cardiorespiratory fitness on executive function and prefrontal oxygenation in older adults - Said Mekari; Olivier Dupuy; Ricardo Martins; Kailey Evans; Derek S. Kimmerly; Sarah Fraser; Heather F. Neyedli (GeroScience, 2019)

Transforming growth factor-β promotes basement membrane fibrosis, alters perivascular cerebrospinal fluid distribution, and worsens neurological recovery in the aged brain after stroke - Matthew D. Howe; J. Weldon Furr; Yashasvee Munshi; Meaghan A. Roy-O’Reilly; Michael E. Maniskas; Edward C. Koellhoffer; John d’Aigle; Lauren H. Sansing; Louise D. McCullough; Akihiko Urayama (GeroScience, 2019)

Cerebral venous congestion promotes blood-brain barrier disruption and neuroinflammation, impairing cognitive function in mice - Gabor A. Fulop; Chetan Ahire; Tamas Csipo; Stefano Tarantini; Tamas Kiss; Priya Balasubramanian; Andriy Yabluchanskiy; Eszter Farkas; Attila Toth; Ádám Nyúl-Tóth; Peter Toth; Anna Csiszar; et al. (GeroScience, 2019)

Treatment with the poly(ADP-ribose) polymerase inhibitor PJ-34 improves cerebromicrovascular endothelial function, neurovascular coupling responses and cognitive performance in aged mice, supporting the NAD+ depletion hypothesis of neurovascular aging - Stefano Tarantini; Andriy Yabluchanskiy; Tamas Csipo; Gabor Fulop; Tamas Kiss; Priya Balasubramanian; Jordan DelFavero; Chetan Ahire; Anna Ungvari; Ádám Nyúl-Tóth; Eszter Farkas; Zoltan Benyo; et al. (GeroScience, 2019)

Assessment of age-related decline of neurovascular coupling responses by functional near-infrared spectroscopy (fNIRS) in humans - Tamas Csipo; Peter Mukli; Agnes Lipecz; Stefano Tarantini; Dhay Bahadli; Osamah Abdulhussein; Cameron Owens; Tamas Kiss; Priya Balasubramanian; Ádám Nyúl-Tóth; Rachel A. Hand; Valeriya Yabluchanska; et al. (GeroScience, 2019)

Astrocyte senescence may drive alterations in GFAPα, CDKN2A p14ARF, and TAU3 transcript expression and contribute to cognitive decline - Jed J. Lye; Eva Latorre; Ben P. Lee; Stefania Bandinelli; Janet E. Holley; Nicholas J. Gutowski; Luigi Ferrucci; Lorna W. Harries (GeroScience, 2019)
The accumulation of senescent cells in tissues is causally linked to the development of several age-related diseases; the removal of senescent glial cells in animal models prevents Tau accumulation and cognitive decline. Senescent cells can arise through several distinct mechanisms; one such mechanism is dysregulation of alternative splicing. In this study, we characterised the senescent cell phenotype in primary human astrocytes in terms of SA-β-Gal staining and SASP secretion, and then assessed splicing factor expression and candidate gene splicing patterns. Finally, we assessed associations between expression of dysregulated isoforms and premature cognitive decline in 197 samples from the InCHIANTI study of ageing, where expression was present in both blood and brain. We demonstrate here that senescent astrocytes secrete a modified SASP characterised by increased IL8, MMP3, MMP10, and TIMP2 but decreased IL10 levels. We identified significant changes in splicing factor expression for 10/20 splicing factors tested in senescent astrocytes compared with early passage cells, as well as dysregulation of isoform levels for 8/13 brain or senescence genes tested. Finally, associations were identified between peripheral blood GFAPα , TAU3 , and CDKN2A ( P14 ARF ) isoform levels and mild or severe cognitive decline over a 3–7-year period. Our data are suggestive that some of the features of cognitive decline may arise from dysregulated splicing of important genes in senescent brain support cells, and that defects in alternative splicing or splicing regulator expression deserve exploration as points of therapeutic intervention in the future.

Overexpression of catalase targeted to mitochondria improves neurovascular coupling responses in aged mice - Anna Csiszar; Andriy Yabluchanskiy; Anna Ungvari; Zoltan Ungvari; Stefano Tarantini (GeroScience, 2019)

Accelerated decline in cognition in a mouse model of increased oxidative stress - Sreemathi Logan; Gordon H. Royce; Daniel Owen; Julie Farley; Michelle Ranjo-Bishop; William E. Sonntag; Sathyaseelan S. Deepa (GeroScience, 2019)

Tamoxifen induction of Cre recombinase does not cause long-lasting or sexually divergent responses in the CNS epigenome or transcriptome: implications for the design of aging studies - Ana J. Chucair-Elliott; Sarah R. Ocanas; David R. Stanford; Niran Hadad; Benjamin Wronowski; Laura Otalora; Michael B. Stout; Willard M. Freeman (GeroScience, 2019)

Correction to: Age-related expression of Neurexin1 and Neuroligin3 is correlated with presynaptic density in the cerebral cortex and hippocampus of male mice - Dhiraj Kumar; M. K. Thakur (GeroScience, 2019)

Important regulatory function of transient receptor potential ankyrin 1 receptors in age-related learning and memory alterations of mice - Éva Borbély; Maja Payrits; Ágnes Hunyady; Gréta Mező; Erika Pintér (GeroScience, 2019)

Nicotinamide mononucleotide (NMN) treatment attenuates oxidative stress and rescues angiogenic capacity in aged cerebromicrovascular endothelial cells: a potential mechanism for the prevention of vascular cognitive impairment - Tamas Kiss; Priya Balasubramanian; Marta Noa Valcarcel-Ares; Stefano Tarantini; Andriy Yabluchanskiy; Tamas Csipo; Agnes Lipecz; Dora Reglodi; Xin A. Zhang; Ferenc Bari; Eszter Farkas; Anna Csiszar; et al. (GeroScience, 2019)

Genetic knockout of myosin light chain kinase (MLCK210) prevents cerebral microhemorrhages and attenuates neuroinflammation in a mouse model of vascular cognitive impairment and dementia - David J. Braun; Adam D. Bachstetter; Tiffany L. Sudduth; Donna M. Wilcock; D. Martin Watterson; Linda J. Van Eldik (GeroScience, 2019)

Systolic hypertension-induced neurovascular unit disruption magnifies vascular cognitive impairment in middle-age atherosclerotic LDLr−/−:hApoB+/+ mice - Olivia de Montgolfier; Philippe Pouliot; Marc-Antoine Gillis; Guylaine Ferland; Frédéric Lesage; Nathalie Thorin-Trescases; Éric Thorin (GeroScience, 2019)

Sulforaphane - role in aging and neurodegeneration - Roberto Santín-Márquez; Adriana Alarcón-Aguilar; Norma Edith López-Diazguerrero; Niki Chondrogianni; Mina Königsberg (GeroScience, 2019)

Exploratory and locomotor activity, learning and memory functions in somatostatin receptor subtype 4 gene-deficient mice in relation to aging and sex - Nikolett Szentes; Valéria Tékus; Violetta Mohos; Éva Borbély; Zsuzsanna Helyes (GeroScience, 2019)

Anti-inflammatory agent, OKN-007, reverses long-term neuroinflammatory responses in a rat encephalopathy model as assessed by multi-parametric MRI: implications for aging-associated neuroinflammation - Rheal A. Towner; Debra Saunders; Nataliya Smith; Rafal Gulej; Tyler McKenzie; Brandy Lawrence; Kathryn A. Morton (GeroScience, 2019)

Lipopolysaccharide exposure in a rat sepsis model results in hippocampal amyloid-β plaque and phosphorylated tau deposition and corresponding behavioral deficits - Ryan A. Kirk; Raymond P. Kesner; Li-Ming Wang; Qi Wu; Rheal A. Towner; John M. Hoffman; Kathryn A. Morton (GeroScience, 2019)

Validation of a geropathology grading system for aging mouse studies - Jessica M. Snyder; Timothy A. Snider; Marcia A. Ciol; John E. Wilkinson; Denise M. Imai; Kerriann M. Casey; Jose G. Vilches-Moure; Christina Pettan-Brewer; Smitha P. S. Pillai; Sebastian E. Carrasco; Shabnam Salimi; Warren Ladiges (GeroScience, 2019)

Validation of a digitally delivered visual paired comparison task: reliability and convergent validity with established cognitive tests - Joshua L. Gills; Jordan M. Glenn; Erica N. Madero; Nick T. Bott; Michelle Gray (GeroScience, 2019)

The association of anxio-depressive disorders and depression with motoric cognitive risk syndrome: results from the baseline assessment of the Canadian longitudinal study on aging - Harmehr Sekhon; Gilles Allali; Olivier Beauchet (GeroScience, 2019)

Nicotinamide mononucleotide (NMN) supplementation promotes anti-aging miRNA expression profile in the aorta of aged mice, predicting epigenetic rejuvenation and anti-atherogenic effects - Tamas Kiss; Cory B. Giles; Stefano Tarantini; Andriy Yabluchanskiy; Priya Balasubramanian; Tripti Gautam; Tamas Csipo; Ádám Nyúl-Tóth; Agnes Lipecz; Csaba Szabo; Eszter Farkas; Jonathan D. Wren; et al. (GeroScience, 2019)

Effect of caloric restriction and rapamycin on ovarian aging in mice - Driele N. Garcia; Tatiana D. Saccon; Jorgea Pradiee; Joao A. A. Rincón; Kelvin R. S. Andrade; Monique T. Rovani; Rafael G. Mondadori; Luis A. X. Cruz; Carlos C. Barros; Michal M. Masternak; Andrzej Bartke; Jeffrey B. Mason; et al. (GeroScience, 2019)

Heterogeneity of healthy aging: comparing long-lived families across five healthy aging phenotypes of blood pressure, memory, pulmonary function, grip strength, and metabolism - Megan M. Marron; Mary K. Wojczynski; Ryan L. Minster; Robert M. Boudreau; Paola Sebastiani; Stephanie Cosentino; Bharat Thyagarajan; Svetlana V. Ukraintseva; Nicole Schupf; Kaare Christensen; Mary Feitosa; Thomas Perls; et al. (GeroScience, 2019)

An expanding GSK3 network: implications for aging research - Dylan C. Souder; Rozalyn M. Anderson (GeroScience, 2019)