The latest study by Yuanhan Yang and colleagues, published in Cell (September 2024), offers a pioneering look into the anti-aging effects of metformin on primates, a crucial step in bridging the gap between preclinical findings in animals and potential human applications.
This article delves into the comprehensive 40-month research on adult male cynomolgus monkeys and explores how metformin could be the key to decelerating aging and enhancing cognitive function, opening new frontiers in geroprotective medicine.
Key findings of the study
The study, centered around adult male cynomolgus monkeys, rigorously explored how metformin, a drug widely used to manage type 2 diabetes, impacts aging in non-human primates.
Previous studies in rodents and small mammals had hinted at metformin’s potential as a geroprotective agent, but this research marks the first major investigation into its effects on primates, especially using advanced biological aging clocks to measure the pace of aging.
1. Brain atrophy prevention and cognitive enhancement
One of the standout findings of this research is the neuroprotective effects of metformin. Over the 40-month study period, metformin treatment slowed brain aging by approximately 6 years compared to control subjects. This significant finding was accompanied by measurable improvements in cognitive function.
Brain imaging, combined with cognitive testing, revealed that the drug not only preserved brain structure but also elevated performance on tasks that gauge memory, learning, and problem-solving.
These findings align with previous research that suggests brain atrophy is a significant marker of aging and cognitive decline, which is strongly associated with diseases such as Alzheimer’s and Parkinson’s. By mitigating brain atrophy, metformin showcases its potential as a protective agent against age-related neurodegeneration.
2. Slowed aging across multiple tissues
Metformin’s, a biguanides compound, benefits extended beyond the brain, decelerating the aging process across a variety of tissues in the male primates. The study utilized a multi-disciplinary approach, applying transcriptomics, DNA methylomics, plasma proteomics, and metabolomics to assess the biological age of tissues like the liver, kidneys, and muscles. The combination of these advanced biological markers, often referred to as “aging clocks,” enabled the researchers to precisely quantify metformin’s impact.
Across these diverse tissue types, metformin consistently slowed the accumulation of aging markers, suggesting a broad and systemic deceleration of aging. This comprehensive analysis reinforces metformin’s potential to impact whole-body aging, rather than just isolated systems.
3. Geroprotection mediated by Nrf2 activation
A key molecular mechanism behind metformin’s geroprotective effect, identified in the study, is the activation of Nrf2 (nuclear factor erythroid 2–related factor 2). Nrf2 is a transcription factor that plays a critical role in regulating the body’s response to oxidative stress, a major contributor to aging and age-related diseases.
Metformin appears to activate Nrf2 in neurons, reducing oxidative damage and inflammation, which are significant drivers of neurodegenerative disorders. By stimulating Nrf2, metformin helps protect neurons from the cumulative damage of aging, which translates into preserved brain function and structure.
This discovery has profound implications for therapeutic strategies aimed at protecting the brain and other tissues from age-related decline. Nrf2 activation could become a target for future drugs designed to mimic or enhance metformin’s effects.
Future research directions
The findings from the Cell study by Yang et al. underscore metformin’s potential to decelerate aging and preserve cognitive function, offering a critical breakthrough in longevity research. This study is the first to demonstrate the broad systemic effects of metformin on aging in primates, providing a strong foundation for future clinical trials in humans. By activating protective pathways such as Nrf2 and slowing the biological aging clock, metformin could represent a major leap forward in the quest for longer, healthier lives.
As we look toward the future, the prospect of using metformin, or similar compounds, to delay aging and its associated diseases opens up exciting new possibilities for extending healthspan and improving quality of life in aging populations.
