New drug class could reverse age-related muscle weakness

As we age, muscle strength peaks around 35, but gradually weakens, accelerating after 60. This decline, even with regular exercise, cannot be entirely stopped. Reduced muscle strength leads to an increased risk of falls, fractures, and limited mobility, affecting the ability to perform daily tasks and reducing quality of life. However, there is growing potential to not only slow down this process but also reverse it, offering a new way to combat age-related muscle decline and preserve strength and independence as we grow older. 

What excites you about your new drug that is designed to maintain and increase muscle strength in older adults?

Answer: Our drug will help aging adults stay fully active, physically and mentally fit, and engaged with their families and communities. It will empower seniors to retain their independence and productive contributions to society.

Stan Watowich

NNMT inhibitors

That’s where NNMT inhibitors come in—an exciting new class of drugs that could change how we age. These innovative drugs have shown incredible potential in boosting muscle strength and improving overall muscle health. In a recent study, NNMT inhibitors significantly increased muscle strength in older animals. In fact, in studies with aged mice, these drugs doubled the strength gains compared to what exercise alone could achieve. And here’s the best part: when combined with exercise, NNMT inhibitors led to a remarkable 60% increase in muscle strength.

Exercise is widely known to reduce muscle fat, which is crucial for maintaining muscle health. A recent study found that NNMT inhibitors produced a similar effect in older mice, significantly reducing muscle fat even in those that did not exercise. Fat levels in treated sedentary mice dropped by over 30%, equalling levels seen in mice subjected to intensive exercise. These findings suggest that NNMT inhibitors could mimic the fat-reducing effects of exercise, presenting a promising new approach to addressing age-related muscle decline. 

The science behind NNMT inhibitors

The science behind these findings is truly fascinating. Researchers delved deep into muscle tissue to understand how NNMT inhibitors work at a molecular level. They discovered that these drugs trigger unique mechanisms that enhance muscle function and composition. By analysing over 2,500 proteins in the muscles of treated mice, they found that NNMT inhibitors specifically targeted and altered the expression of certain proteins linked to muscle atrophy. Remarkably, the treatment downregulated proteins associated with muscle wasting and upregulated others that are crucial for maintaining muscle structure and function.

Moreover, NNMT inhibitors didn’t just affect a few proteins—they made significant changes across various cellular processes. For example, these drugs boosted the production of proteins involved in protein synthesis and ribosome biogenesis— cellular processes that are often disrupted as we age. By enhancing these processes, NNMT inhibitors seem to improve muscle repair and growth, offering hope for maintaining muscle health well into our later years.

Researchers also examined cellular metabolites, the small molecules involved in metabolism, in the muscles of mice. NNMT inhibitors had a notable effect, with sedentary mice given NNMT inhibitors showing metabolomic changes resembling those seen in exercised mice. These changes included increased levels of AMP, essential for energy production, and reduced lactate, which can accumulate during muscle fatigue. The impact was even greater when the inhibitors were used alongside exercise, suggesting that NNMT inhibitors can enhance the metabolic benefits of physical activity on muscle function.

A new approach to preserve muscle health

This recent study shows that NNMT inhibitors offer a new approach to preserving muscle health as we age. By targeting critical molecular pathways, these drugs can sustain and increase muscle strength, reduce muscle fat, and enhance muscle metabolism—all essential for maintaining mobility and independence during ageing. Whether used alone or in combination with exercise, NNMT inhibitors represent a promising advance in the fight against age-related muscle weakness and potentially many other muscle disorders.

The loss of muscle mass and strength with age goes beyond appearance; it affects daily life and makes everyday tasks, such as carrying groceries or climbing stairs, more challenging and is linked to serious health risks, including chronic disease, cognitive decline, loss of independence, and shorter life expectancy. However, addressing age-related muscle decline is not only a medical issue but a public health priority. In the U.S., there are 55 million people over 60. This number is projected to rise to 74 million in the next decade, and as it does, healthcare demands will increase and Medicare costs will double.

Conclusions

Since NNMT inhibitors offer the potential of maintaining the strength, mobility, and independence of older adults, these drugs could allow seniors to remain active in both the workforce and their communities, while also easing healthcare costs. 

Developing a once-daily oral drug that can rebuild muscle strength in older adults might seem like a big task, but this recent research shows that it’s not only possible—it’s within reach. Imagine a world where ageing doesn’t mean losing strength but gaining a new lease on life. That’s the promise of NNMT inhibitors, and it’s an exciting future that could soon become a reality.

🔬🧫🧪🔍🤓👩‍🔬🦠🔭📚

Journal reference

Dimet-Wiley, A. L., Latham, C. M., Brightwell, C. R., Neelakantan, H., Keeble, A. R., Thomas, N. T., … & Watowich, S. J. (2024). Nicotinamide N-methyltransferase inhibition mimics and boosts exercise-mediated improvements in muscle function in aged mice. Scientific reports, 14(1), 15554. https://doi.org/10.1038/s41598-024-66034-9