Harvard Medical School NMN Research

Aging is often associated with the decline of our blood vessels, which can impact our overall vitality. Recent research conducted by Harvard Medical School suggests that reversing the aging process of blood vessels could be the key to restoring youthful energy, at least in mice. The study, published in Cell on March 22, reveals the cellular mechanisms involved in vascular aging and its effects on muscle health. The researchers successfully reversed this process in mice, shedding light on potential therapies for humans.

Health Benefits

Understanding Vascular Aging

As we age, our smallest blood vessels deteriorate, leading to reduced blood flow and insufficient oxygen supply to organs and tissues. Vascular aging contributes to various disorders, including cardiac and neurologic conditions, muscle loss, impaired wound healing, and overall frailty. The endothelial cells that line blood vessels play a crucial role in maintaining healthy blood vessels and supplying oxygen-rich blood. However, as these cells age, blood vessels deteriorate, fail to regenerate, and blood flow decreases, particularly affecting muscles that heavily rely on a robust blood supply.

The Role of SIRT1 and NAD+

To uncover the mechanisms behind the decline in blood flow and muscle vitality, the researchers focused on the protein SIRT1 and its interaction with NAD+. Previous studies have shown that SIRT1 delays aging and extends lifespan in yeast and mice. The loss of SIRT1 is triggered by the decline of NAD+, a regulator of protein interactions and DNA repair. NAD+ levels also decrease with age, leading to reduced SIRT1 activity.

The researchers discovered that NAD+ and SIRT1 form a vital link between endothelial cells and muscle cells, enabling proper communication and blood vessel growth.

Impaired Blood Flow and Muscle Atrophy

In young mice, SIRT1 signaling activates and promotes the formation of new capillaries, which supply oxygen and nutrients to tissues and organs. However, as NAD+ and SIRT1 activity decline over time, blood flow decreases, leaving muscles deprived of essential nutrients and oxygen.

The researchers conducted experiments where they deleted SIRT1 in the endothelial cells of young mice, leading to reduced capillary density and exercise tolerance. They observed that these cells became less responsive to growth-stimulating proteins released by muscles during exercise, contributing to muscle atrophy and blood vessel deterioration.

Reversing Vascular Aging

To counteract the decline of SIRT1 and NAD+, the researchers explored the use of NMN (nicotinamide mononucleotide), a compound that boosts NAD+ levels. In lab experiments, NMN treatment enhanced the growth capacity and reduced cell death in human and mouse endothelial cells. When administered to aging mice, NMN restored blood vessel density and improved blood flow to muscles.

Most significantly, the treated mice exhibited a remarkable increase in exercise capacity compared to untreated mice. The researchers also explored the combined effects of NMN and sodium hydrosulfide (NaHS), another compound that enhances SIRT1 activity. The combination further improved exercise capacity in older mice.

The Potential for Therapeutic Advances

The findings of this study hold promise for developing therapeutic interventions for older individuals who may not have the option of regular physical activity. The researchers aim to replicate these findings and develop small-molecule drugs based on NMN that can mimic the effects of exercise. Such treatments could enhance blood flow and oxygenation in muscles and other tissues.

Additionally, these therapies may be beneficial for promoting new blood vessel growth in organs affected by reduced blood supply and oxygen, such as in heart attacks and ischemic strokes. However, caution is necessary to avoid stimulating tumor growth through excessive blood supply.

Conclusion

The research conducted at Harvard Medical School provides valuable insights into the mechanisms of vascular aging and its impact on muscle health. By targeting the decline of NAD+ and SIRT1, the study offers a potential avenue for reversing vascular aging and restoring youthful vitality in mice. While further research is needed to determine the effectiveness of these findings in humans, clinical trials for safety are already underway.

If successful, these therapeutic advances could revolutionize the treatment of age-related disorders and provide hope for individuals with limited mobility or those unable to engage in regular physical activity. The ultimate goal is to develop NMN-based drugs that replicate the beneficial effects of exercise, promoting enhanced blood flow, oxygenation, and overall tissue health. By unraveling the secrets of vascular aging, this research opens up new possibilities for improving the well-being and quality of life of aging individuals.