NAD+ metabolism and its roles in cellular processes during ageing
Covarrubias AJ, Perrone R, Grozio A, Verdin E
Published in Nature Reviews Molecular Cell Biology
Abstract
Detailed review of NAD+ metabolism decline during aging and its impact on cellular processes including energy metabolism, DNA repair, and circadian rhythms. Discusses therapeutic strategies for NAD+ restoration.
Methodology
Review in Nature Reviews Molecular Cell Biology of NAD+ biosynthesis and consumption pathways, the causes of NAD+ decline with age, and precursor-based restoration strategies.
Key Findings
Tissue NAD+ falls with age through both reduced salvage synthesis and increased consumption by CD38, PARPs and sirtuins, with chronic inflammation a major driver. Restoring NAD+ with precursors such as NR and NMN reliably raises NAD+ levels and improves healthspan markers in rodents. Human trials confirm precursors raise blood NAD+ but have not yet demonstrated meaningful clinical benefit.
Conclusions
NAD+ decline is a well-supported feature of ageing biology and a plausible therapeutic target, but raising NAD+ in humans has not yet been shown to translate into functional or longevity benefits.
Limitations
Narrative review weighted towards rodent and cell data; human trials to date are small, short and focused on biomarker rather than clinical endpoints; optimal precursor, dose and target tissue remain undefined.
Outcomes Measured
Tissue NAD+ falls with age through both reduced salvage synthesis and increased consumption by CD38, PARPs and sirtuins, with chronic inflammation a major driver. Restoring NAD+ with precursors such as NR and NMN reliably raises NAD+ levels and improves healthspan markers in rodents. Human trials confirm precursors raise blood NAD+ but have not yet demonstrated meaningful clinical benefit.
Tissue NAD+ falls with age through both reduced salvage synthesis and increased consumption by CD38, PARPs and sirtuins, with chronic inflammation a major driver. Restoring NAD+ with precursors such as NR and NMN reliably raises NAD+ levels and improves healthspan markers in rodents. Human trials confirm precursors raise blood NAD+ but have not yet demonstrated meaningful clinical benefit.
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