Metformin Shows Promise in Slowing Cellular Aging in Primates, Suggesting Potential for Human Application
Key Insights
A new study demonstrates that long-term metformin use has protective effects on various tissues and organs in primates, including the liver, heart, lungs, and muscles.
Metformin mitigated cerebral cortex atrophy, enhanced cognitive function, and slowed periodontal bone loss in monkeys, suggesting direct action on neurons independent of blood sugar regulation.
The research identified that metformin activates the Nrf2 (search)-mediated antioxidant gene expression network in the brain, delaying cellular aging and reducing biological age markers.
Researchers have found that metformin, a common drug used to treat type 2 diabetes (search), may significantly slow down cellular aging. A recent study published in Cell details how long-term metformin use in primates led to protective effects on various tissues and organs, offering potential implications for human aging.
The collaborative research, involving teams from the Institute of Zoology (IOZ) (search) at CAS, the Beijing Institute of Genomics, and IOZ, examined the effects of metformin on aging using Cynomolgus monkeys (Macaca fascicularis), which share physiological similarities with humans.
Study Design and Methodology
For 40 months, researchers conducted a comprehensive study involving medical imaging, multi-tissue pathological analysis, multi-omics, routine blood tests, and physiological assessments. Male monkeys were administered metformin to monitor its impact on the aging process.
Key Findings
The study revealed that long-term metformin use had significant protective effects on the liver, heart, lungs, and muscles. Notably, it mitigated atrophy of the cerebral cortex, enhanced cognitive function, and slowed periodontal bone loss. These results suggest that metformin may act directly on neurons and other cells, independent of its role in blood sugar regulation.
Researchers identified that metformin activates the Nrf2 (search)-mediated antioxidant gene expression network in the brain, delaying the effects of cellular aging. This provides a scientific basis for metformin’s geroprotective properties and could pave the way for future therapeutic advancements.
Impact on Biological Age
Machine learning models were used to evaluate the systemic effects of metformin on aging, allowing for precise evaluations of the drug’s benefits. 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 15 to 18 human years.
The effects of metformin were most pronounced in the frontal lobe of the brain and the liver. 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, equivalent to about 15 to 18 years in humans.
Implications for Geriatric Medicine
"This is a significant step forward in understanding the biology of aging," said one of the lead scientists. The study highlights a 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, targeting 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 (search) and cardiovascular conditions (search), has grown. This study demonstrates the possibility of targeting the aging process itself, rather than merely treating its consequences, potentially reducing age-related decline and enhancing the quality of life in older adults.