Sirtuins

07 July 2023

Sirtuins and Bio-Rejuvenation: A Pathway to Health and Longevity

Introduction

Sirtuins, a family of proteins with diverse biological functions, have attracted considerable attention for their potential role in bio-rejuvenation. Studies suggest these proteins may contribute to increased lifespan and improved health through various mechanisms, such as promoting genomic stability, modulating metabolism, and alleviating oxidative stress (1).

Understanding Sirtuins

Sirtuins are a class of proteins known for their role in regulating cellular health. They have seven distinct types (SIRT1-7), each localized to different regions within the cell and performing diverse roles. Sirtuins are NAD+-dependent deacetylases that regulate the function of proteins involved in crucial biological processes, including DNA repair, cell cycle, metabolism, and stress response (2).

Sirtuins and Aging

There is growing evidence that sirtuins play a crucial role in the aging process. For instance, overexpression of SIRT1, the most studied member of the sirtuin family, has been linked to extended lifespan in multiple organisms, including yeast, worms, and flies. In mammals, SIRT1 has been associated with improved metabolic efficiency, reduced inflammation, and enhanced stress resistance, traits often observed in long-lived organisms (3).

Sirtuins in Bio-Rejuvenation

Given their role in regulating cellular health, sirtuins are of significant interest for bio-rejuvenation. Several strategies are currently under investigation to leverage the power of sirtuins for health and longevity:

• Caloric restriction: This dietary intervention, known to extend lifespan in a variety of organisms, increases the levels of NAD+, a coenzyme that activates sirtuins. Consequently, caloric restriction is believed to promote longevity partly through sirtuin activation (4).

• NAD+ boosters: Several supplements, including nicotinamide riboside and nicotinamide mononucleotide, are marketed as NAD+ boosters, aiming to enhance sirtuin activity. Preliminary studies in mice suggest these supplements might have positive effects on health and lifespan (5).

• Sirtuin-activating compounds (STACs): Resveratrol, a compound found in grapes and red wine, is a known STAC. It has been shown to activate SIRT1, mimicking the effects of caloric restriction and potentially promoting health and longevity (6).

Conclusion

While the role of sirtuins in bio-rejuvenation is promising, further research is needed to fully understand their potential and to translate findings from model organisms to humans. Advancements in this field could open up new avenues for healthspan extension, disease prevention, and bio-rejuvenation.

References

1. Sinclair, D. A., & Guarente, L. (2014). Small molecule allosteric activators of sirtuins. Annual review of pharmacology and toxicology, 54, 363-380.

2. Choudhary, C., Kumar, C., Gnad, F., Nielsen, M. L., Rehman, M., Walther, T. C., ... & Mann, M. (2009). Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science, 325(5942), 834-840.

3. Kanfi, Y., Naiman, S., Amir, G., Peshti, V., Zinman, G., Nahum, L., ... & Cohen, H. Y. (2012). The sirtuin SIRT6 regulates lifespan in male mice. Nature, 483(7388), 218-219.

4. Ingram, D. K., & Roth, G. S. (2015). Calorie restriction mimetics: can you have your cake and eat it, too?. Ageing research reviews, 20, 46-62.

5. Imai, S. I., & Guarente, L. (2014). NAD+ and sirtuins in aging and disease. Trends in cell biology, 24(8), 464-471.

6. Bitterman, K. J., Anderson, R. M., Cohen, H. Y., Latorre-Esteves, M., & Sinclair, D. A. (2002). Inhibition of silencing and accelerated aging by nicotinamide, a putative negative regulator of yeast sir2 and human SIRT1. Journal of Biological Chemistry, 277(47), 45099-45107.