Use of Metformin in Biological Anti-Aging

Metformin has been a mainstay and frontline medication for treatment of type 2 diabetes for decades. It is now gaining popularity in the longevity field and studies are underway with prevention of certain cancers too.

Current studies are showing a reduction in cancer risk and mortality particularly for tumors of the lung, colon, pancreas and breast. Research is currently targeted in humans and have already shown that metformin can increase lifespan in mice by nearly 6% along with improved cholesterol and physical performance.

The TAME (Targeting Aging with Metformin) Trial is a large clinical trial ran by leading researchers that will prove that aging can be treated. Metformin targets the metabolic, oxidative and inflammatory pathways.

These three areas are associated with the development of age-related conditions. Despite such widespread use and research, the exact mechanisms by which metformin regulates these fundamental pathways in aging and diseases is not fully known, thus the current research.

Intermittent metformin treatment, when initiated in mice, even later in life, has been shown to provide health benefits and longevity. There is longstanding evidence that the decline in mitochondrial function with aging, may contribute to age-associated dysregulation in energy and increased predisposition to age-related diseases.

The mitochondria are the powerhouse of the cell. Dysfunction as seen with aging, can have implications on inflammation, autophagy (the cells’ ability to remove and/or clean up) and oxidative stress. Metformin thus, lowers and inhibits the cellular processes of mitochondria dysfunction.

Metformin also targets stem cells and maintenance of stem cell number and function can help combat age-associated loss of rejuvenation potential and promote tissue repair. Telomeres play a crucial role in protecting chromosomal ends from degradation caused by incomplete DNA replications. With aging and stress exposure, these regions of our DNA are vulnerable to deterioration. Progressive telomere shortening is found to be associated with biological aging and age-related morbidities, frailty, and mortality.

Studies are limited on suggesting that metformin targets telomere length, although, in diabetic individuals, studies have suggested reduced telomere shortening and further studies are targeted at understanding prevention and maintenance of telomere integrity. The risks and benefits should be considered when starting any medication.

The positive effects of metformin include increased healthspan and decreased mortality. Minor side effects can be seen with metformin to include minor gastrointestinal discomfort. Microbiome changes could be seen and can reduce absorption of vitamin B12 in a small percentage of individuals. Monitoring levels at least annually is very important and replacement is usually necessary for resolution.

Patients who have problems with their kidneys, liver or heart, should also be cautious. As always, it is important to discuss with your provider if this medication is right for you. At Empowered Health, our precision medicine approach provides cutting edge, individualized care that targets the whole patient and is proactive to optimize the quality of one’s life with scientifically studied strategies for healthy aging.

References

TAME Trial. Targeting Aging with Metformin. (2021). Retrieved from http://www.afar.org

Kulkarni, A., Gubbi, S. & Barzilai, N. (2020, April 20). Benefits of Metformin in Attenuating the Hallmark of Aging. Retrieved from http://ncbi.nlm.nih.gov

UpToDate. (2022). Metformin: Drug Information. Retrieved from http://UpToDate.com

The University of Arizona Andrew Weil Center for Integrative Medicine. Pharmacotherapy: Integrative Diabetes Treatment. (2022). Retrieved from https://integrativemedicine.arizona.edu