2023.05.06 02:43
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2023.05.06 03:18
2023.05.06 09:45
https://www.frontiersin.org/articles/10.3389/fendo.2021.718942/full
Conclusions
Based on a 60-year history of use as an anti-diabetic drug for the treatment of T2DM, metformin is accepted as a comparatively safe drug. Metformin is no longer protected by patents and thus is comparatively inexpensive. Collectively, these attributes together with an extensive literature supportive of benefits in the settings of diabetes, obesity, cardiovascular disease and, arguably, cancer and dementia could justify its wider use as a prophylactic to offset the effects of aging and enhance healthspan and lifespan. In this review we have also highlighted and critiqued some of the key clinical and laboratory-based studies that provide data supportive of the hypothesis that metformin, independent of its anti-hyperglycemic actions, has benefits that in principle can slow cellular aging and enhance healthspan and lifespan. Metformin, via its direct protective effects on vascular function, may slow the aging process via improved blood flow and provide protection against age-related cognitive decline. However, not all of the data is supportive and metformin, as shown in C. elegans and mice, may be less effective, or ineffective, in older humans. We have also stressed that, based on the pharmacokinetic properties of metformin, caution is needed before extrapolating from in vitro cell-based studies done with comparatively high metformin concentrations to clinical effectiveness with plasma concentrations in the range of 20 micromolar or lower. This issue is a particular concern with the in vitro studies reporting an anti-proliferative effect of metformin and promoting its use as an adjunct for the treatment of various cancers as, in most of these studies, the concentration/dose of metformin that have been used would most likely prove toxic in patients. Furthermore, a dependence on the use of metformin as a prophylactic to delay aging could serve to decrease the incentive to pursue the proven benefits of lifestyle changes such as improved diet and exercise. Moreover, the long-term chronic use of metformin would require attention to the potential occurrence of vitamin B12 deficiency. On this basis, we conclude that metformin should not be seen as a ‘quick fix’ panacea for aging at the expense of non-pharmacologic interventions such as diet, exercise, and related lifestyle changes. Indeed, the use of metformin may negate some of the positive effects of exercise and lifestyle and less favorable effects in older subjects as was also emphasized by the Diabetes Prevention Program (265, 266). On the more positive side, we do accept that the use of metformin in the treatment of patients with T2DM is associated with a positive benefit on healthspan. By lowering plasma glucose levels and body weight, metformin improves the metabolic profile of the patient and thereby reduces the severity and risk of other diseases associated with diabetes such as cardiovascular, cancer, and also neurodegenerative diseases (267). The importance of the gut-brain axis in mediating the therapeutic effects of metformin is also emphasized, as are the potential beneficial effects of metformin to protect against neurodegenerative disorders. Finally, although the evidence for lifespan expansion in mammalian species is not conclusive, a full analysis and follow-up of clinical trials, including MILES and TAME, may provide more definitive answers as to whether metformin should be promoted beyond its use to treat T2DM, as a drug that enhances both healthspan and lifespan. Of particular importance is the need for evidence from prospective studies of the effects of metformin on subjects of different age groups, free of chronic diseases, which will help determine if metformin has benefits beyond those of reducing pre-existing disease burden.
It is 3:30 AM in the morning.
After an early morning start in Irvine, CA., I and my wife just drove 1,040 miles to arrive
at my home in Castle Rock, CO the night before the last.
As my sleeping time got messed up during a long trip,
I woke up early and was not able to get back to sleep.
What else can I do? I opened my "aging" desktop computer and suddenly met this article
in the news. A rather remarkable surprise! Or, a drug company commercial?
It is very interesting and, in a way, it seems to be making some sense.
Having gone over the hill of my 80s, I will need everything to slow down my aging process.
I am to see my family doctor, a geriatrician, next week and I am going to ask him about this.