Metformin is a drug used primarily for the treatment of type 2 diabetes. Multiple studies conducted in the last 4 decades have demonstrated that metformin extends lifespan of several model organisms (from yeast to rodents). Metformin has also been found to decrease all-cause mortality in humans suffering from diabetes. In addition to its anti-aging effects metformin may also reduce the risk of heart disease and cancer.
What is Hutchinson-Gilford Progeria Syndrome?
Hutchinson-Gilford Progeria Syndrome (HGPS) is a rare inherited illness that causes premature aging and patients typically die around their 13th birthday from a heart attack or stroke. Though some can live to their 20s before passing away. HGPS is caused by a mutation in the lamin A gene leading to the production of an abnormal form of the lamin A protein called progerin. Lamin A is involved in the construction of the interior ‘skeleton’ of the cell nucleus. Cell nuclei from patients who suffer from HGPS show an abnormal morphology (blebbing, see image). Exactly how the accumulation of progerin leads to accelerated aging is not yet fully understood. Interestingly, low levels of progerin also accumulate in the nucleus during ‘normal’ aging.
The benefits of Metformin
In a new paper published in Experimental Dermatology researchers show that metformin reduces cell senescence, decreases the production of reactive oxygen species (ROS), improved nuclear morphology, and reduced DNA damage in skin cells derived HGPS patients. Furthermore, metformin treatment reduced progerin levels. The authors also tested metformin in normal aged mice and found that it improves antioxidant defences in these mice. This result is in line with the observed reduction in ROS levels in the skin cells from HGPS patients treated with metformin.
These results are in line with those from a paper published last year in npj Aging and Mechanisms of Disease. In this study it was shown that metformin treatment reduced progerin levels and improved the morphology of the cell nucleus.
Future research will be needed to investigate if metformin also improves lifespan in a mice model of HGPS and eventually in human patients. Also the role of progerin in ‘normal’ aging remains largely unexplored. Finally, is the reduction in progerin production by metformin (partially) responsible for the lifespan extending effects of metformin in laboratory animals?
Park SK, Shin OS (2017). Metformin Alleviates Aging Cellular Phenotypes in Hutchinson-Gilford Progeria Syndrome Dermal Fibroblasts. Exp Dermatol [Epub ahead of print].
Egesipe AL et al. (2016). Metformin decreases progerin expression and alleviates pathological defects of Hutchinson–Gilford progeria syndrome cells. npj Aging Mech Dis 2: 16026.