Anti-Aging Effect of Metformin: A Molecular and Therapeutical Perspective

Abstract

: Aging is a time-dependent inevitable process, in which cellular homeostasis is affected, which has an impact on tissue function. This represents a risk factor for the development of numerous non-transmissible diseases. In consequence, the scientific community continues to search for therapeutic measures capable of improving quality of life and delaying cellular aging. At the center of this research is metformin, a widely used drug in Type 2 Diabetes Mellitus treatment that has a reduced adverse effects profile. Furthermore, there is evidence that this drug has beneficial health effects that go beyond its anti-hyperglycemic properties. Among these effects, its geronto-protection capability stands out. There is growing evidence that points out to an increased life expectancy as well as quality of life in model organisms treated with metformin. Therefore, there is an abundance of research centered on elucidating the mechanism through which metformin has its anti-aging effects. Among these, the AMPK, mTORC1, SIRT1, FOXO, NF.kB, and DICER1 pathways can be mentioned. Furthermore, studies have highlighted the possibility of a role for gut microbiome in these processes. The next step is the design of clinical essays that have as a goal evaluating the efficacy and safety of metformin as an anti-aging drug in humans to create a paradigm in the medical horizon. The question being if metformin is in fact the new anti-aging therapy in humans?

Metformin Inhibits BMP9-Induced Proliferation and Differentiation of Human Lung Fibroblasts via AMPK Signaling

“…Metformin, a rst-line drug for the clinical treatment of type 2 diabetes, is widely used in metabolic diseases due to its high effectiveness, safety and low cost. Increasing experimental and clinical studies have shown that metformin has multiple health bene ts in many disorders [11,19,29,36,42,43 ]. For instance, metformin was found to have anti-cancer, anti-aging and anti-oxidant effects.…”

Can Blood-Circulating Factors Unveil and Delay Your Biological Aging?

“…Nobel prize winner Dr. Rita Levi-Montalcini, who discovered the NGF, applied NGF in the form of eye drops for the rest of her life and lived 103 years [171]. Although the role of NGF in significantly prolonging life expectancy has not been clearly demonstrated, some studies have shown its effect on the suspension of certain senile diseases and prolongation of the functioning of vital body systems [12,42,122,167,[172][173][174][175]. Decreased NGF levels are associated with cognitive decline and Alzheimer's disease.…”

“…Blocking factors that negatively affect lifespan is a reasonable strategy to prevent early disability and prolong the active life of older people. Among such strategies, tested in the clinical practice or which will be translated to the clinical practice, one can highlight overcoming the insulin resistance by diet restriction [8], increasing FGF21 in blood circulation, pharmacological treatment of insulin resistance (e.g., with dehydroepiandrosterone and metformin) [12,14], stimulation of tissue repair by GH, oxytocin, GDF11 and TIMP2 [203], vascular regeneration with bFGF, EGF, VEGF, PDGF-AB, and BMP9, preventing the development of "inflammaging" by administering anti-inflammatory molecules, including COX-2 inhibitors, leukotriene receptor antagonists, TIMP2, or other matrix metalloproteinase inhibitors [210,263], overcoming the cell senescence by administration of TM5441 analogs, optimizing the autophagy and mitophagy with mTOR inhibitors (rapamycin analogs) [264], with TGF-β inhibitors [110,264], antioxidant therapy [265,266], reduction of NAD+ exhaustion [73]. The indicators and mechanisms discussed above reflect the natural and pathological aging processes.…”

“…Individual aging can accelerate due to stress associated with social upheaval and personal problems [2,9]. Assessment of individual biological age and aging markers' identification are necessary to predict life expectancy, to evaluate the risk of developing age-related diseases, and to work out the measurable parameters of geroprotection for the rapidly expanding anti-aging research [10][11][12][13][14].…”

Prestroke Metformin Use on the 1‐Year Prognosis of Intracerebral Hemorrhage Patients with Type 2 Diabetes

“…In addition to treating diabetes, metformin also plays an essential role in the treatment of other diseases, such as anticancer [ 7 ], antiaging [ 8 , 9 ], treatment of gestational hypertension [ 10 ] and hypertension [ 11 ], and weight loss [ 12 ]. In addition, metformin use could reduce the risk of hypertension [ 13 ] and stroke [ 14 ].…”