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Written by Nitin Sreekumar ‘25
Edited by Andrew Ni '26
Centuries ago, the herb Galega officinalis—once prized in Europe for treating digestive issues, lowering fevers, and even battling the plague—held a secret waiting to be discovered. Within its leaves, scientists later uncovered guanidine, a compound with remarkable blood sugar-lowering properties. This discovery led to the creation of metformin, which has since become a game-changer in modern medicine. Today, metformin is not just a treatment for diabetes; it's a global powerhouse with over 120 million prescriptions written worldwide, earning its place as the second most prescribed medication on the planet [2].
While metformin is best known for its role in managing diabetes, researchers are now uncovering a host of additional health benefits. Beyond controlling blood sugar, studies suggest it may reduce the risks of cancer, dementia, and stroke, and most intriguingly, it could hold the key to slowing down the aging process itself. This positions metformin as a potential multi-purpose drug with benefits that reach far beyond its original purpose [2].
The quest to defy aging has fascinated humanity for centuries. From ancient tales of immortality to the fabled search for the Fountain of Youth, humans have long sought ways to extend life. In modern times, science has taken up this challenge, and while aging remains inevitable, research on animals has shown it may be possible to delay its effects, which include tissue dysfunction and physiological deterioration leading to age-related diseases such as neurodegenerative, cardiovascular, and diabetic disorders. Metformin, in particular, has shown promise in slowing down the physiological aging process in organisms such as nematodes, fruit flies, and rodents—hinting at the possibility that it could one day help humans as well.
Until recently, whether metformin could actually delay aging in higher animals remained unknown. A breakthrough study led by Yang et al. changed that by administering metformin to adult male cynomolgus monkeys for 40 months. The results were remarkable: the drug provided neuroprotection, preserving brain structure, enhancing cognitive ability, and even reversing signs of brain aging by approximately six years. This effect was linked to the activation of Nrf2, a transcription factor and antioxidant, which plays a key role in regulating the body's antioxidant defenses [3].
The researchers conducted detailed experiments, including organism-wide and genome-wide RNA-seq analyses, to investigate metformin’s impact on aging at the molecular level. They compared young, middle-aged, and old monkeys and found that metformin helped stabilize aging-related fluctuations in gene expression across multiple tissues. Importantly, metformin reactivated pathways typically suppressed by aging—such as those involved in development, morphogenesis, Wnt signaling, lipid metabolism, and DNA repair. These findings point to metformin’s ability to combat chronic inflammation, a hallmark of aging, by reducing inflammation in organs like the liver and stomach and preventing immune cell infiltration in the lungs, liver, and kidneys [3].
To further understand how metformin slows aging, the team developed "single-nucleus transcriptomic aging clocks," referred to as sn-transcriptAge, to track cellular aging at different life stages. They found that metformin not only slowed aging in the liver by downregulating TNF-a, which in turn reduced fibrosis (commonly seen in aging livers), but also protected and enhanced the metabolic function of hepatocytes. The drug’s protective effects extend to the brain, where it provided neuroprotection and slowed cognitive decline in older monkeys, largely through the activation of Nrf2, which upregulated antioxidant genes typically suppressed during aging [3].
While this study offers exciting prospects, there’s still much to explore before metformin can officially be hailed as an anti-aging wonder drug for humans. More studies are needed, particularly across different sexes and larger groups of animals, to better understand its potential. Yet, this research is an essential stepping stone, sparking hope that pharmaceuticals could one day combat age-related diseases and even slow down the aging process itself. With metformin already offering a multitude of health benefits, the possibility of it improving not just our healthspan but perhaps even our lifespan brings us closer to a future where staying "forever young" might not be just a dream.
References
Yang Y, Lu X, Liu N, Ma S, Zhang H, Zhang Z, et al. Metformin decelerates aging clock in male monkeys. Cell. 2024 Sep;S0092867424009140.
Mohammed I, Hollenberg MD, Ding H, Triggle CR. A Critical Review of the Evidence That Metformin Is a Putative Anti-Aging Drug That Enhances Healthspan and Extends Lifespan. Front Endocrinol. 2021 Aug 5;12:718942.
Williams V. Mayo Clinic News Network. 2016 [cited 2024 Oct 16]. Mayo Clinic Minute: Anti-Aging Pill. Available from: https://newsnetwork.mayoclinic.org/discussion/mayo-clinic-minute-anti-aging-pill/
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