Hallmarks of Health

Cell, Год журнала: 2020, Номер 184(1), С. 33 - 63

Опубликована: Дек. 18, 2020

Язык: Английский

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Autophagy and the hallmarks of aging

Ageing Research Reviews, Год журнала: 2021, Номер 72, С. 101468 - 101468

Опубликована: Сен. 24, 2021

Язык: Английский

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Senescence mechanisms and targets in the heart

Cardiovascular Research, Год журнала: 2021, Номер 118(5), С. 1173 - 1187

Опубликована: Май 5, 2021

Abstract Cellular senescence is a state of irreversible cell cycle arrest associated with ageing. Senescence different cardiac types can direct the pathophysiology cardiovascular diseases (CVDs) such as atherosclerosis, myocardial infarction, and fibrosis. While age-related telomere shortening represents major cause replicative senescence, senescent also be induced by oxidative stress, metabolic dysfunction, epigenetic regulation, among other stressors. It critical that we understand molecular pathways lead to cellular consequences in order develop new therapeutic approaches treat CVD. In this review, discuss mechanisms explore how (including cardiomyocytes, endothelial cells, fibroblasts, vascular smooth muscle valve interstitial cells) CVD, highlight potential target prevent or

Язык: Английский

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The effects of metformin on autophagy

Biomedicine & Pharmacotherapy, Год журнала: 2021, Номер 137, С. 111286 - 111286

Опубликована: Янв. 30, 2021

Metformin is the first-line option for treating newly diagnosed diabetic patients and also involved in other pharmacological actions, including antitumor effect, anti-aging polycystic ovarian syndrome prevention, cardiovascular action, neuroprotective etc. However, mechanisms of metformin actions were not fully illuminated. Recently, increasing researches showed that autophagy a vital medium playing actions. Nevertheless, results on effects inconsistent. Apart from few clinical evidences, more data focused kinds no-clinical models. First, many studies could induce via number signaling pathways, AMPK-related pathways (e.g. AMPK/mTOR, AMPK/CEBPD, MiTF/TFE, AMPK/ULK1, AMPK/miR-221), Redd1/mTOR, STAT, SIRT, Na+/H+ exchangers, MAPK/ERK, PK2/PKR/AKT/ GSK3β, TRIB3. Secondly, some process inhibiting autophagy, such as (AMPK/NF-κB undetermined pathways), Hedgehog, miR-570-3p, miR-142-3p, MiR-3127-5p. Thirdly, two types PI3K/AKT/mTOR endoplasmic reticulum (ER) stress bidirectionally impact effectiveness autophagy. Finally, multiple signal reviewed collectively terms affecting The combining its discussed. It would help better apply to treat diseases term mediating

Язык: Английский

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Metformin for Cardiovascular Protection, Inflammatory Bowel Disease, Osteoporosis, Periodontitis, Polycystic Ovarian Syndrome, Neurodegeneration, Cancer, Inflammation and Senescence: What Is Next?

ACS Pharmacology & Translational Science, Год журнала: 2021, Номер 4(6), С. 1747 - 1770

Опубликована: Ноя. 1, 2021

Diabetes is accompanied by several complications. Higher prevalence of cancers, cardiovascular diseases, chronic kidney disease (CKD), obesity, osteoporosis, and neurodegenerative diseases has been reported among patients with diabetes. Metformin the oldest oral antidiabetic drug can improve coexisting complications Clinical trials observational studies uncovered that metformin remarkably prevent or alleviate polycystic ovarian syndrome (PCOS), cancer, periodontitis, neuronal damage inflammation, inflammatory bowel (IBD), tuberculosis, COVID-19. In addition, proposed as an antiaging agent. Numerous mechanisms were shown to be involved in protective effects metformin. activates LKB1/AMPK pathway interact intracellular signaling pathways molecular mechanisms. The modifies biologic function NF-κB, PI3K/AKT/mTOR, SIRT1/PGC-1α, NLRP3, ERK, P38 MAPK, Wnt/β-catenin, Nrf2, JNK, other major molecules network. It also regulates expression noncoding RNAs. Thereby, regulate metabolism, growth, proliferation, tumorigenesis, senescence. Additionally, modulates immune response, autophagy, mitophagy, endoplasmic reticulum (ER) stress, apoptosis exerts epigenetic effects. Furthermore, protects against oxidative stress genomic instability, preserves telomere length, prevents stem cell exhaustion. this review, on each will discussed using results recent meta-analyses, clinical trials, studies. Thereafter, it meticulously explained how reprograms alters cellular interactions modify presentations diseases.

Язык: Английский

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Vascular dementia: From pathobiology to emerging perspectives

Ageing Research Reviews, Год журнала: 2024, Номер 96, С. 102278 - 102278

Опубликована: Март 19, 2024

Vascular dementia (VaD) is the second most common type of dementia. VaD synonymous with ageing, and its symptoms place a significant burden on health wellbeing older people. Despite identification substantial number risk factors for VaD, pathological mechanisms underpinning this disease remain to be fully elucidated. Consequently, biogerontological imperative exists highlight modifiable lifestyle which can mitigate against developing VaD. This review will critically examine some have been revealed modulate risk. The survey commences by providing an overview putative are associated pathobiology Next, influence examined. Finally, emerging treatment avenues including epigenetics, gut microbiome, pro-longevity pharmaceuticals discussed. By drawing key evidence together, it our hope that used inform future experimental investigations in field.

Язык: Английский

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Metformin targets mitochondrial complex I to lower blood glucose levels

Science Advances, Год журнала: 2024, Номер 10(51)

Опубликована: Дек. 18, 2024

Metformin is among the most prescribed antidiabetic drugs, but primary molecular mechanism by which metformin lowers blood glucose levels unknown. Previous studies have proposed numerous mechanisms acute glucose, including inhibition of mitochondrial complex I electron transport chain (ETC). Here, we used transgenic mice that globally express Saccharomyces cerevisiae internal alternative NADH dehydrogenase (NDI1) protein to determine whether glucose-lowering effect oral administration requires ETC in vivo. NDI1 a yeast enzyme complements loss mammalian function and insensitive pharmacologic inhibitors metformin. We demonstrate expression attenuates metformin’s ability lower under standard chow high-fat diet conditions. Our results indicate targets glucose.

Язык: Английский

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Metformin to decrease COVID-19 severity and mortality: Molecular mechanisms and therapeutic potential

Biomedicine & Pharmacotherapy, Год журнала: 2021, Номер 144, С. 112230 - 112230

Опубликована: Окт. 7, 2021

The COVID-19 pandemic caused by the coronavirus SARS-CoV-2 has become a serious challenge for medicine and science. Analysis of molecular mechanisms associated with clinical manifestations severity identified several key points immune dysregulation observed in infection. For diabetic patients, factors including higher binding affinity virus penetration, decreased clearance T cell function, increased susceptibility to hyperinflammation, cytokine storm may make these patients susceptible more severe course disease. Metabolic changes induced diabetes, especially hyperglycemia, can directly affect immunometabolism lymphocytes part affecting activity mTOR protein kinase signaling pathway. High enhance progression diabetes due activation effector proinflammatory subpopulations and, conversely, low promotes differentiation T-regulatory cells. Interestingly, metformin, an extensively used antidiabetic drug, inhibits AMPK. Therefore, AMPK and/or inhibition mTOR-mediated pathway be important new target drug therapy cases mostly reducing level pro-inflammatory storm. These suggestions have been partially confirmed retrospective analyzes mellitus hospitalized COVID-19.

Язык: Английский

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Cellular Senescence Affects Cardiac Regeneration and Repair in Ischemic Heart Disease

Aging and Disease, Год журнала: 2021, Номер 12(2), С. 552 - 552

Опубликована: Янв. 1, 2021

Ischemic heart disease (IHD) is defined as a syndrome of ischemic cardiomyopathy. Myogenesis and angiogenesis in the myocardium are important for cardiomyocyte (CM) survival, improving cardiac function decreasing progression failure after IHD. Cellular senescence state permanent irreversible cell cycle arrest caused by stress that results decline cellular functions, such proliferation, migration, homing, differentiation. In addition, senescent cells produce senescence-associated secretory phenotype (SASP), which affects tissue microenvironment surrounding secreting proinflammatory cytokines, chemokines, growth factors, extracellular matrix degradation proteins. The accumulation cardiovascular-related cells, including vascular endothelial (VECs), smooth muscle (VSMCs), CMs progenitor an risk factor cardiovascular diseases, aging, atherosclerotic plaque formation, myocardial infarction (MI) ventricular remodeling. This review summarizes processes angiogenesis, myogenesis this focuses on relationship between mechanism senescence. Finally, we discuss potential therapeutic strategy MI targeting cells.

Язык: Английский

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Proteostasis in aging-associated ocular disease

Molecular Aspects of Medicine, Год журнала: 2022, Номер 88, С. 101157 - 101157

Опубликована: Ноя. 29, 2022

Vision impairment has devastating consequences for the quality of human life. The cells and tissues associated with visual process must function throughout one's life span maintain homeostasis despite exposure to a variety insults. Maintenance proteome is termed proteostasis, vital normal cellular functions, especially at an advanced age. Here we describe basic aspects from protein synthesis folding degradation, discuss current status field particular focus on major age-related eye diseases: macular degeneration, cataract, glaucoma. Our intent allow vision scientists determine where how harness proteostatic machinery extending functional in aging retina, lens, trabecular meshwork. Several common themes have emerged these having vastly different metabolisms. Continued insults, including chronic stress advancing age, increases burden reduces fidelity degradation machineries ubiquitin-proteasome autophagy-lysosome systems that recognize remove damaged proteins. This "double jeopardy" results exponential accumulation cytotoxic proteins We conclude discussion challenges maintaining appropriate balance pathways, suggest harnessing capacities should provide new opportunities design interventions attenuating diseases before they limit sight.

Язык: Английский

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