Common diabetes drug found to significantly slow down aging

Scientists from the Chinese Academy of Sciences (CAS) have made a groundbreaking discovery about aging, raising the question: is it reversible?

Their research sheds light on how metformin, a common medication for type 2 diabetes, can slow cellular aging in primates, offering a potential breakthrough for slowing human aging as well. This advancement could lead to new therapeutic interventions for aging, providing hope for future generations.

The research, a collaborative effort between LIU Guanghui’s team from the Institute of Zoology (IOZ) of CAS, ZHANG Weiqi’s team from the Beijing Institute of Genomics, and QU Jing’s team from IOZ, was published in the prestigious journal Cell.

Using Cynomolgus monkeys (Macaca fascicularis), a species with physiological similarities to humans, the scientists set out to examine how metformin affects aging over an extended period. This approach opens a window into human aging research, thanks to these monkeys' comparable biological structures.

For 40 months, the researchers conducted a comprehensive study, employing techniques such as medical imaging, multi-tissue pathological analysis, and multi-omics, alongside routine blood tests and physiological assessments. By applying metformin therapy to male monkeys, they monitored how it impacted their aging process.

Their findings were compelling. Long-term use of metformin showed significant protective effects on various tissues and organs, including the liver, heart, lungs, and muscles. Notably, it mitigated the atrophy of the cerebral cortex, enhanced cognitive function, and slowed periodontal bone loss. This suggests that metformin may be acting directly on neurons and other cells, independent of its usual function in blood sugar regulation.

The study identified that metformin activates the Nrf2-mediated antioxidant gene expression network in the brain, delaying the effects of cellular aging. This mechanism provides a strong scientific basis for metformin’s geroprotective properties and could pave the way for future therapeutic advancements aimed at slowing down aging.

In addition to its direct impact on neurons, the researchers employed machine learning models to evaluate the overall systemic effects of metformin on aging. These models helped them build a comprehensive assessment of tissue and organ aging, allowing for precise evaluations of the drug’s benefits.

The results indicated a significant reduction in biological age markers in primates treated with metformin. DNA methylation age, transcriptome age, and plasma protein and metabolite age were all reduced. The most substantial reduction observed was equivalent to 18 human years, a striking finding that highlights metformin’s potential in delaying biological aging.

The effects of metformin were most pronounced in the frontal lobe of the brain and the liver, two areas particularly vulnerable to aging. High-precision aging clocks at the single-cell level demonstrated that the biological age of neural cells in the brain and hepatocytes in the liver was reduced by approximately five to six years.

When translated to humans, this is equivalent to about 15 to 18 years. The study’s thorough and methodical approach offers new paradigms and standards for evaluating human aging interventions.

As the researchers emphasized, the study’s implications are far-reaching. "This is a significant step forward in understanding the biology of aging," said one of the lead scientists. It also highlights the shift in geriatric medicine from treating individual chronic conditions to addressing the aging process as a whole. This transition represents a new frontier in healthcare, one that targets the root causes of aging to improve overall health and longevity.

As human life expectancy continues to rise, the focus on aging-related diseases, such as Alzheimer’s and cardiovascular conditions, has grown. However, this study demonstrates the possibility of targeting the aging process itself, rather than merely treating its consequences. With metformin showing such potential, future research could lead to broader applications for humans, possibly helping to reduce age-related decline and enhance the quality of life in older adults.

This research opens new doors to understanding and potentially reversing aspects of aging. By using metformin, scientists have not only expanded knowledge about cellular aging but also laid the groundwork for future therapies aimed at delaying the aging process. This represents a major leap forward in the field of geriatric medicine, signaling a future where aging may not be an inevitable decline, but a process that can be managed and perhaps even reversed.

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