Metformin is an old drug that has helped diabetics keep blood sugar under control for over 70 years. Despite its long history, in recent years the scientific community has begun to suspect that this molecule hides other, much more revolutionary properties: the ability to extend human life. Research from Hamad Bin Khalifa University in Qatar has just taken stock of the results that have emerged in recent years regarding the anti-aging effects of metformin, clarifying the biochemical mechanisms that allow this substance to act on processes linked to senescence, and lining up the reasons why it would be important to broaden and deepen investigations into a molecule which – the authors write – has the potential to revolutionize the study of longevity.
The origins of the study
Metformin has been synthesized for over a century and has been used clinically since the 1950s, so much so that it is classified among essential medicines by the WHO. Although it is therefore a well-known drug, the understanding of its metabolic ramifications is still under development. To shed light on the issue, experts from the Qatari university analyzed a vast corpus of previous studies, isolating the molecular processes triggered by the intake.
In addition to its primary role in glycemic control, the substance has proven capable of activating a protein known as Amp-activated kinase (Ampk), a sort of energy sensor of the organism, the stimulation of which involves the inhibition of another protein known as Mtor kinase, a step that intensifies the autophagy processes with which cells dispose of and recycle damaged or no longer necessary components. The result of these molecular steps is a structural decrease in oxidative stress and a simultaneous improvement in insulin sensitivity within the body’s tissues. Two mechanisms – the researchers write – which contribute synergistically to slowing down the aging of individual cells.
Epigenetic changes and the intestinal microbiome
The research described in the study also highlights pathways of epigenetic alteration (i.e. changes in gene expression not linked to DNA mutations) linked to the use of the drug. Specifically, the molecule stimulates the production and conservation of the Tet2 enzyme, another key player in the processes of cellular aging and senescence. “The greater stability in the levels of this enzyme induced by metformin intake leads to a reduction in abnormal methylation patterns that cause genomic instability during aging,” explains Jarra Manneh, researcher at Hamad Bin Khalifa University. “And this results in greater genomic stability and a reduction in the risk of age-related diseases, and therefore generates a methylation profile that tends to remain youthful.”
The data examined in the study also suggests a protective action on bacterial flora. The constant intake of metformin generates alterations in the intestinal microbiome that attenuate systemic inflammatory responses, strengthen intestinal barrier defenses and support metabolic balance.
The limits of today’s research
Although there is a large volume of indirect indications on the active properties of the molecule against aging, the concrete application encounters methodological obstacles. The vast majority of evaluations conducted so far on humans have been purely observational and have focused on patients already affected by specific pathologies such as diabetes. And even if literature data suggest an effective extension of life in patients who regularly use metformin, it is difficult to isolate the real effect of the active ingredient on completely healthy subjects and clearly determine whether the prolonged life conditions depend on an effective systemic improvement or only on the effective control of pre-existing diseases.
Future practical applications
To overcome the limitations of the research carried out to date, several large-scale trials are about to start in recent years which should investigate the effects of metformin in people without type 2 diabetes. One above all, the Tame (Targeting Aging with Metformin) study, which aims to enroll over three thousand participants in fourteen American clinical centers, and to follow their evolution over a period of six years. The information collected during these trials will have the potential to confirm the measurements observed in the laboratory, and according to the authors of the review, could revolutionize the clinical approach to longevity.
While awaiting the results, experts however urge caution before attributing anti-aging abilities to the molecule which are yet to be demonstrated. “More research is needed, particularly randomized clinical trials in non-diabetic populations, to investigate the drug’s epigenetic and microbiome-mediated effects, as well as to develop metformin-responsive biomarkers of aging,” the researchers write. “By combining clinical, molecular and population data, metformin may yet prove to be the wonder drug that redefines the limits of healthy aging.”