Abstract
Nicotinamide riboside (NR) is a precursor to NAD + , a vital molecule for cellular energy metabolism whose levels decline with age. Aging is associated with loss of cognitive and immune function, alterations in hematological parameters, and increased vulnerability to stress. Although NR supplementation can mitigate age-related declines, it remains uncertain whether these positive effects persist when the organism is exposed to chronic physiological stress. We investigated this by exposing aged mice to NR supplementation alongside daily physiological stress and assessed various indices before and after treatment. Our results revealed that 6 weeks of NR supplementation protected against stress-induced thrombocytopenia and increased the frequencies of B and T cells. However, NR also heightened stress sensitivity, as evidenced by increased anxiety-like behaviors, while not affecting cognitive function. These findings suggest a dual role for NR in potentially enhancing immune function while exacerbating behavioral responses to stress. Future research on NR should consider stress as a variable to optimize its therapeutic usage in aging populations. Graphical Abstract