Benefits of Metformin in Attenuating the Hallmarks of Aging

Cell Metabolism, Journal Year: 2020, Volume and Issue: 32(1), P. 15 - 30

Published: April 24, 2020

Language: Английский

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Cancer as a disease of old age: changing mutational and microenvironmental landscapes

British Journal of Cancer, Journal Year: 2020, Volume and Issue: 122(7), P. 943 - 952

Published: Feb. 11, 2020

Abstract Why do we get cancer mostly when are old? According to current paradigms, the answer is simple: mutations accumulate in our tissues throughout life, and some of these contribute cancers. Although necessary for development, a number studies shed light on roles ageing exposure-dependent changes tissue landscapes that determine impact oncogenic cellular fitness, placing carcinogenesis into an evolutionary framework. Natural selection has invested somatic maintenance maximise reproductive success. Tissue not only ensures functional robustness but also prevents occurrence through periods likely reproduction by limiting events cells. Indeed, organisms ranging from flies humans revealing conserved mechanisms eliminate damaged or oncogenically initiated cells tissues. Reports existence striking numbers clones normal how this clonal architecture with age external exposure noxious substances provide critical insight early stages development. A major challenge biology will be integration epidemiology data theory carcinogenesis, which could have large addressing risk treatment.

Language: Английский

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A Critical Review of the Evidence That Metformin Is a Putative Anti-Aging Drug That Enhances Healthspan and Extends Lifespan

Frontiers in Endocrinology, Journal Year: 2021, Volume and Issue: 12

Published: Aug. 5, 2021

The numerous beneficial health outcomes associated with the use of metformin to treat patients type 2 diabetes (T2DM), together data from pre-clinical studies in animals including nematode, C. elegans, and mice have prompted investigations into whether has therapeutic utility as an anti-aging drug that may also extend lifespan. Indeed, clinical trials, MILES (Metformin In Longevity Study) TAME (Targeting Aging Metformin), been designed assess potential benefits drug. Preliminary analysis results indicate induce transcriptional changes; however it remains controversial is protective those subjects free disease. Furthermore, despite for over 60 years anti-diabetic drug, cellular mechanisms by which exerts either its actions remain unclear. this review, we critically evaluated literature investigated effects on aging, healthspan lifespan humans well other species. preparing particular attention placed strength reproducibility quality study protocols respect pharmacokinetic pharmacodynamic properties metformin. We conclude support benefits, evidence increases controversial. However, via ability reduce early mortality various diseases, diabetes, cardiovascular disease, cognitive decline cancer, can improve thereby extending period life spent good health. Based available aging are primarily indirect metabolism result anti-hyperglycemic action, enhancing insulin sensitivity, reduction oxidative stress endothelium vascular function.

Language: Английский

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Metformin: Is it a drug for all reasons and diseases?

Metabolism, Journal Year: 2022, Volume and Issue: 133, P. 155223 - 155223

Published: May 29, 2022

Metformin was first used to treat type 2 diabetes in the late 1950s and 2022 remains first-choice drug daily by approximately 150 million people. An accumulation of positive pre-clinical clinical data has stimulated interest re-purposing metformin a variety diseases including COVID-19. In polycystic ovary syndrome improves insulin sensitivity. 1 may help reduce dose. Meta-analysis from studies link reduction incidence cancer. Clinical trials, MILES (Metformin Longevity Study), TAME (Targeting Aging with Metformin), have been designed determine if can offset aging extend lifespan. Pre-clinical suggest that metformin, via suppression pro-inflammatory pathways, protection mitochondria vascular function, direct actions on neuronal stem cells, protect against neurodegenerative diseases. also studied for its anti-bacterial, -viral, -malaria efficacy. Collectively, these raise question: Is all diseases? It unclear as whether putative beneficial effects are secondary an anti-hyperglycemic insulin-sensitizing drug, or result other cellular actions, inhibition mTOR (mammalian target rapamycin), anti-viral actions. Clarification is sought ex vivo based use high concentrations be translated into benefits, they reflect 'Paracelsus' effect. The environmental impact no known metabolites, another emerging issue linked endocrine disruption fish, extensive T2D raised concerns over human reproduction. objectives this review to: 1) evaluate mechanism(s) action metformin; 2) analyze controversial evidence metformin's effectiveness treatment than diabetes; 3) assess reproducibility data, finally 4) reach informed conclusion reasons. We conclude primary benefits antihyperglycaemic secondarily contribute reduced risk number thereby enhancing healthspan. However, like improving endothelial function independent glucose homeostasis add therapeutic

Language: Английский

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Interconnections between Inflammageing and Immunosenescence during Ageing

Cells, Journal Year: 2022, Volume and Issue: 11(3), P. 359 - 359

Published: Jan. 21, 2022

Acute inflammation is a physiological response to injury or infection, with cascade of steps that ultimately lead the recruitment immune cells clear invading pathogens and heal wounds. However, chronic arising from continued presence initial trigger, dysfunction signalling and/or effector pathways, harmful health. While successful ageing in older adults, including centenarians, associated low levels inflammation, elevated increases risk poor health death. Hence has been described as one seven pillars ageing. Age-associated sterile, chronic, low-grade commonly termed inflammageing-it not simply consequence increasing chronological age, but also marker biological ageing, multimorbidity, mortality risk. inflammageing was initially thought be caused by "continuous antigenic load stress", reports last two decades describe much more complex phenomenon involving cellular senescence system. In this review, we explore some main sources consequences context immunosenescence highlight potential interventions. particular, assess contribution age-associated identify patterns pro- anti-inflammatory markers characteristic inflammageing, alterations system finally ways diet, exercise, pharmacological interventions can reduce thus, improve later life

Language: Английский

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Immune Clearance of Senescent Cells to Combat Ageing and Chronic Diseases

Cells, Journal Year: 2020, Volume and Issue: 9(3), P. 671 - 671

Published: March 10, 2020

Senescent cells are generally characterized by permanent cell cycle arrest, metabolic alteration and activation, apoptotic resistance in multiple organs due to various stressors. Excessive accumulation of senescent numerous tissues leads chronic diseases, tissue dysfunction, age-related diseases organ ageing. Immune can remove cells. Immunaging or impaired innate adaptive immune responses result persistent Although senolytics—drugs that selectively inducing their apoptosis—are recent hot topics making significant research progress, senescence immunotherapies using cell-mediated clearance emerging promising strategies fight ageing diseases. This short review provides an overview the progress date concerning cell-caused ageing, as well regulation small-molecule drugs clinical trials different roles elimination Mounting evidence indicates immunotherapy targeting combats subsequently extends healthy lifespan.

Language: Английский

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Metformin: A Review of Potential Mechanism and Therapeutic Utility Beyond Diabetes

Drug Design Development and Therapy, Journal Year: 2023, Volume and Issue: Volume 17, P. 1907 - 1932

Published: June 1, 2023

Metformin has been designated as one of the most crucial first-line therapeutic agents in management type 2 diabetes mellitus. Primarily being an antihyperglycemic agent, metformin also a plethora pleiotropic effects on various systems and processes. It acts majorly by activating AMPK (Adenosine Monophosphate-Activated Protein Kinase) cells reducing glucose output from liver. decreases advanced glycation end products reactive oxygen species production endothelium apart regulating lipid metabolism cardiomyocytes, hence minimizing cardiovascular risks. Its anticancer, antiproliferative apoptosis-inducing malignant might prove instrumental malignancy organs like breast, kidney, brain, ovary, lung, endometrium. Preclinical studies have shown some evidence metformin's neuroprotective role Parkinson's disease, Alzheimer's multiple sclerosis Huntington's disease. exerts its through varied pathways intracellular signalling exact mechanism majority them remains yet to be clearly defined. This article extensively reviewed benefits details for molecule boon conditions diabetes, prediabetes, obesity, polycystic ovarian metabolic derangement HIV, cancers aging.

Language: Английский

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Gene Therapy-Mediated Partial Reprogramming Extends Lifespan and Reverses Age-Related Changes in Aged Mice

Cellular Reprogramming, Journal Year: 2024, Volume and Issue: 26(1), P. 24 - 32

Published: Feb. 1, 2024

Aging is a complex progression of changes best characterized as the chronic dysregulation cellular processes leading to deteriorated tissue and organ function. Although aging cannot currently be prevented, its impact on life- healthspan in elderly can potentially minimized by interventions that aim return these optimal Recent studies have demonstrated partial reprogramming using Yamanaka factors (or subset; OCT4, SOX2, KLF4; OSK) reverse age-related vitro vivo. However, it still unknown whether subset) are capable extending lifespan aged wild-type (WT) mice. In this study, we show systemically delivered adeno-associated viruses, encoding an inducible OSK system, 124-week-old male mice extend median remaining 109% over WT controls enhance several health parameters. Importantly, observed significant improvement frailty scores indicating were able improve along with increasing lifespan. Furthermore, human keratinocytes expressing exogenous OSK, epigenetic markers age reversal, suggesting potential reregulation genetic networks younger healthier state. Together, results may important implications for development age-associated diseases elderly.

Language: Английский

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Metformin: Past, Present, and Future

Current Diabetes Reports, Journal Year: 2024, Volume and Issue: 24(6), P. 119 - 130

Published: April 3, 2024

Language: Английский

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Cholesterol-Rich Lipid Rafts as Platforms for SARS-CoV-2 Entry

Frontiers in Immunology, Journal Year: 2021, Volume and Issue: 12

Published: Dec. 16, 2021

Since its appearance, the Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2), causal agent of Disease 2019 (COVID-19), represents a global problem for human health that involves host lipid homeostasis. Regarding, rafts are functional membrane microdomains with highly and tightly packed molecules. These regions enriched in sphingolipids cholesterol recruit concentrate several receptors molecules involved pathogen recognition cellular signaling. Cholesterol-rich have multiple functions viral replication; however, their role SARS-CoV-2 infection remains unclear. In this review, we discussed novel evidence on cholesterol-rich as platform entry, where such angiotensin-converting enzyme-2 (ACE-2), heparan sulfate proteoglycans (HSPGs), Toll-like (TLRs), transmembrane serine proteases (TMPRSS), CD-147 HDL-scavenger receptor B type 1 (SR-B1) recruited interaction spike protein. FDA-approved drugs statins, metformin, hydroxychloroquine, cyclodextrins (methyl-β-cyclodextrin) can disrupt to regulate key immune signaling pathways triggered by infection. Taken together, better knowledge SARS-CoV-2-host interactions will provide valuable insights into pathogenesis identification therapeutic targets.

Language: Английский

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