Metformin as Anti-Aging Therapy: Is It for Everyone?

Abstract

Metformin is the most widely prescribed oral hypoglycemic medication for type 2 diabetes worldwide. Metformin also retards aging in model organisms and reduces the incidence of aging-related diseases such as neurodegenerative disease and cancer in humans. In spite of its widespread use, the mechanisms by which metformin exerts favorable effects on aging remain largely unknown. Further, not all individuals prescribed metformin derive the same benefit and some develop side effects. Before metformin finds its way to mainstay therapy for anti-aging, a more granular understanding of the effects of the drug in humans is needed. This review provides an overview of recent findings from metformin studies in aging and longevity and discusses the use of metformin to combat aging and aging-related diseases.

Keywords: aging; lysosome; metformin; mitochondria; personalized medicine; type 2 diabetes.

Figure 1.. Significant events in metformin use in diabetes and aging-related diseases.

Metformin-like compounds such as galegine are the active compounds in the French lilac Galega officinalis that has been used since medieval times to treat diabetes-like symptoms. Metformin, phenformin and buformin were synthesized by Werner and Bell in 1922, and studies determined that biguanides lowered blood glucose in laboratory animals in the mid 1920s. Owing to studies in humans by the French physician-scientist Dr. Jean Sterne, metformin went into use in Europe in the 1950s and was later approved in the US in 1995. Its US approval was delayed due to concerns over lactic acidosis, far more likely with its sister drugs phenformin and buformin. In the early 2000s, studies at the National Institutes of Health determined that metformin extends lifespan and healthspan in laboratory mice, and shortly thereafter metformin was found in observational studies to reduce morbidity and mortality from aging-associated diseases such as cancer in humans. Metformin extends the lifespan of the roundworm Caenorhabditis elegans by up to 50%, a discovery that has enabled genetic dissection of the pathways necessary for metformin longevity effects. We predict that the future of metformin use to combat aging in humans will involve the use of personalized medicine approaches.

Figure 2.. Metformin effects on longevity in model organisms and in humans.

Metformin has been shown to have pro-longevity and healthspan extending properties in the roundworm Caenorhabditis elegans, mice, and humans. In other model organisms such as Drosophila (fruit fly) and rats, similar benefit has not been identified. Although data from prospective clinical trials in humans on metformin in aging are only just planned or beginning to emerge, widespread use of the drug in aging in otherwise healthy individuals requires far more granular understanding of its effects, and the genetic and environmental determinants of its success in promoting aging versus potential detrimental effects. T2D, type 2 diabetes.