NAD⁺ as a central metabolic hub Regulating the hallmarks of aging: Mechanisms and therapeutic implications.
Level 5 - mechanism / opinion, no new human data
Narrative review of mechanistic literature with no primary clinical data or systematic review methodology.
PubMed 41812700 · doi:10.1016/j.mad.2026.112174
What was done
This narrative review synthesized mechanistic literature examining how nicotinamide adenine dinucleotide (NAD⁺) metabolism interacts with fourteen biological hallmarks of aging. The authors evaluated preclinical models of neurodegenerative, cardiometabolic, and musculoskeletal diseases, as well as oncological risks and metabolic pathways involved in NAD⁺ synthesis and consumption.
What was found
The abstract reports no quantitative data or numerical outcomes. It describes qualitative findings that age-related decline in NAD⁺ impairs genomic, epigenetic, mitochondrial, and proteostatic stability. While preclinical restoration of NAD⁺ counters functional decline in several disease models, NAD⁺ also displays a context-dependent duality by sustaining the pro-tumorigenic senescence-associated secretory phenotype (SASP) and supporting established tumor growth.
Why it matters
It highlights that uncritical, blanket NAD⁺ supplementation carries potential oncological and tissue-specific risks, advocating for a shift toward targeted precision modulation based on systems biology.
Limits
The abstract provides no quantitative metrics, meta-analytic pooling, or human clinical trial outcomes. Conclusions rely largely on preclinical disease models and mechanistic hypotheses that may not translate directly to human safety or efficacy.
Cited by
- supports Cellular NAD levels decline substantially after age 40 and into the 50s, reducing the activity of sirtuin enzymes.