NAD+ Regulates Heart's Circadian Rhythms During Aging

NAD+ (nicotinamide adenine dinucleotide), a key metabolite that declines with age, now appears to control the heart's internal clock. This study in aging hearts shows that falling NAD+ levels disrupt circadian rhythmicity—the 24-hour cycles that regulate cardiac metabolism, repair, and stress responses. The circadian clock and NAD+ metabolism are tightly intertwined: clock proteins regulate NAD+ synthesis enzymes, while NAD+ influences clock gene expression through sirtuins and other NAD+-dependent pathways. When NAD+ drops with age, this feedback loop breaks down, potentially contributing to cardiovascular disease risk. The findings help explain why boosting NAD+ (through precursors like NMN or NR) shows cardiovascular benefits in some animal studies—it may partially restore circadian regulation. For human longevity, maintaining robust circadian rhythms is increasingly recognized as crucial for health, and this work suggests NAD+ supplementation could support cardiac circadian function. However, most evidence remains preclinical, and we need human trials measuring both NAD+ levels and circadian markers to confirm therapeutic potential.