Researchers: Basil P Hubbard, David A Sinclair
Recent studies in mice have identified single molecules that can delay multiple diseases of aging and extend lifespan. In theory, such molecules could prevent dozens of diseases simultaneously, potentially extending healthy years of life. In this review, we discuss recent advances, controversies, opportunities, and challenges surrounding the development of SIRT1 activators, molecules with the potential to delay aging and age-related diseases. Sirtuins comprise a family of NAD⁺-dependent deacylases that are central to the body’s response to diet and exercise. New studies indicate that both natural and synthetic sirtuin activating compounds (STACs) work via a common allosteric mechanism to stimulate sirtuin activity, thereby conferring broad health benefits in rodents, primates, and possibly humans. The fact that two-thirds of people in the USA who consume multiple dietary supplements consume resveratrol, a SIRT1 activator, underscores the importance of understanding the biochemical mechanism, physiological effects, and safety of STACs.
References
- Evaluation of resveratrol, green tea extract, curcumin, oxaloacetic acid, and medium-chain triglyceride oil on life span of genetically heterogeneous mice.
- Different dietary restriction regimens extend lifespan by both independent and overlapping genetic pathways in C. elegans.
- SIRT1 is required for AMPK activation and the beneficial effects of resveratrol on mitochondrial function.
- The lifespan extension effects of resveratrol are conserved in the honey bee and may be driven by a mechanism related to caloric restriction.
- Resveratrol delays age-related deterioration and mimics transcriptional aspects of dietary restriction without extending life span.
- Age-associated proinflammatory secretory phenotype in vascular smooth muscle cells from the non-human primate Macaca mulatta: reversal by resveratrol treatment.