Senolytics and senomorphics: Natural and synthetic therapeutics in the treatment of aging and chronic diseases

Free Radical Biology and Medicine, Год журнала: 2021, Номер 171, С. 169 - 190

Опубликована: Май 12, 2021

Язык: Английский

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Why Senescent Cells Are Resistant to Apoptosis: An Insight for Senolytic Development

Frontiers in Cell and Developmental Biology, Год журнала: 2022, Номер 10

Опубликована: Фев. 16, 2022

Cellular senescence is a process that leads to state of irreversible cell growth arrest induced by variety intrinsic and extrinsic stresses. Senescent cells (SnCs) accumulate with age have been implicated in various age-related diseases part via expressing the senescence-associated secretory phenotype. Elimination SnCs has potential delay aging, treat extend healthspan. However, once becoming senescent, they are more resistant apoptotic stimuli. Senolytics can selectively eliminate targeting SnC anti-apoptotic pathways (SCAPs). They developed as novel pharmacological strategy diseases. heterogeneity indicates depend on different proteins or for their survival. Thus, better understanding underlying mechanisms resistance will provide new molecular targets development cell-specific broad-spectrum therapeutics clear SnCs. In this review, we discussed latest research progresses challenge senolytic development, described significance regulation apoptosis systematically summarized SCAPs involved

Язык: Английский

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Cellular Senescence: Molecular Targets, Biomarkers, and Senolytic Drugs

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(8), С. 4168 - 4168

Опубликована: Апрель 10, 2022

Cellular senescence is defined as irreversible cell cycle arrest caused by various processes that render viable cells non-functional, hampering normal tissue homeostasis. It has many endogenous and exogenous inducers, closely connected with age, age-related pathologies, DNA damage, degenerative disorders, tumor suppression activation, wound healing, repair. However, the literature replete contradictory findings concerning its triggering mechanisms, specific biomarkers, detection protocols. This may be partly due to wide range of cellular in vivo animal or human models accelerated aging have been used study test senolytic drugs. review summarizes recent senescence, presents some widely models, briefly describes best-known agents.

Язык: Английский

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Targeting senescent cells for a healthier longevity: the roadmap for an era of global aging

Life Medicine, Год журнала: 2022, Номер 1(2), С. 103 - 119

Опубликована: Авг. 9, 2022

Abstract Aging is a natural but relentless process of physiological decline, leading to physical frailty, reduced ability respond stresses (resilience) and, ultimately, organismal death. Cellular senescence, self-defensive mechanism activated in response intrinsic stimuli and/or exogenous stress, one the central hallmarks aging. Senescent cells cease proliferate, while remaining metabolically active and secreting numerous extracellular factors, feature known as senescence-associated secretory phenotype. Senescence physiologically important for embryonic development, tissue repair, wound healing, prevents carcinogenesis. However, chronic accumulation persisting senescent contributes host pathologies including age-related morbidities. By paracrine endocrine mechanisms, can induce inflammation locally systemically, thereby causing dysfunction, organ degeneration. Agents those targeting damaging components phenotype or inducing apoptosis exhibit remarkable benefits both preclinical models early clinical trials geriatric conditions. Here we summarize features outline strategies holding potential be developed interventions. In long run, there an increasing demand safe, effective, clinically translatable senotherapeutics address healthcare needs current settings global

Язык: Английский

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Senescence-induced inflammation: an important player and key therapeutic target in atherosclerosis

European Heart Journal, Год журнала: 2019, Номер 41(31), С. 2983 - 2996

Опубликована: Дек. 4, 2019

Abstract Inflammation is a hallmark and potent driver of pathological vascular remodelling in atherosclerosis. However, current anti-inflammatory therapeutic strategies have shown mixed results. As an alternative perspective on the conundrum chronic inflammation emerging evidence points towards small subset senescent cells as critical player central node driving Senescent belonging to various cell types are dominant source large array pro-inflammatory cytokines additional plaque destabilizing factors, being involved with aspects atherosclerosis pathogenesis. Antagonizing these key agitators local instability may provide causative multi-purpose strategy treat Anti-senescence treatment options translational potential currently development. several questions challenges remain be addressed before novel approaches enter clinical setting.

Язык: Английский

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SQSTM1/p62 and PPARGC1A/PGC-1alpha at the interface of autophagy and vascular senescence

Autophagy, Год журнала: 2019, Номер 16(6), С. 1092 - 1110

Опубликована: Авг. 23, 2019

Defective macroautophagy/autophagy and mitochondrial dysfunction are known to stimulate senescence. The regulator PPARGC1A (peroxisome proliferator activated receptor gamma, coactivator 1 alpha) regulates biogenesis, reducing senescence of vascular smooth muscle cells (VSMCs); however, it is unknown whether autophagy mediates PPARGC1A-protective effects on Using

Язык: Английский

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Autophagy Is Pro-Senescence When Seen in Close-Up, but Anti-Senescence in Long-Shot

Molecules and Cells, Год журнала: 2017, Номер 40(9), С. 607 - 612

Опубликована: Сен. 1, 2017

When mammalian cells and animals face a variety of internal or external stresses, they need to make homeostatic changes so as cope with various stresses.To this end, are equipped two critical stress responses, autophagy cellular senescence.Autophagy senescence share number stimuli including telomere shortening, DNA damage, oncogenic oxidative stress, suggesting their intimate relationship.Autophagy is originally thought suppress by removing damaged macromolecules organelles, yet recent studies also indicated that promotes facilitating the synthesis senescence-associated secretory proteins.These seemingly opposite roles may reflect complex picture autophagic regulation on senescence, different types unique spatiotemporal activation autophagy.Thus, better understanding process will lead us not only elucidate conundrum how plays dual in but helps development new therapeutic strategies for many human diseases associated senescence.We address pro-senescence anti-senescence while focusing potential mechanistic aspects relationship between senescence.

Язык: Английский

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NADPH Oxidases and Mitochondria in Vascular Senescence

International Journal of Molecular Sciences, Год журнала: 2018, Номер 19(5), С. 1327 - 1327

Опубликована: Апрель 29, 2018

Aging is the major risk factor in development of cardiovascular diseases (CVDs), including hypertension, atherosclerosis, and myocardial infarction. Oxidative stress caused by overproduction reactive oxygen species (ROS) and/or reduced expression antioxidant enzymes a contributor to progression vascular senescence, pathologic remodeling wall, disease. Both oxidative inflammation promote process which cells stop proliferating become dysfunctional. This review focuses on role mitochondria nicotinamide adenine dinucleotide phosphate (NADPH) oxidases Nox1 Nox4 their contribution atherosclerosis. Recent findings are reviewed, supporting critical mitochondrial regulator peroxisome proliferator-activated receptor gamma (PPARγ) coactivator-1α (PGC-1α), inflammatory gene nuclear κB (NF-κB), zinc, zinc transporters (ZnTs) ZnT3 ZnT10, angiotensin II (Ang II) function, telomere stability, provides new mechanistic insights into previously proposed unified theory aging.

Язык: Английский

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The chemistry of senescence

Nature Reviews Chemistry, Год журнала: 2019, Номер 3(7), С. 426 - 441

Опубликована: Июнь 13, 2019

Язык: Английский

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Ionizing Radiation-Induced Cellular Senescence in Normal, Non-transformed Cells and the Involved DNA Damage Response: A Mini Review

Frontiers in Pharmacology, Год журнала: 2018, Номер 9

Опубликована: Май 22, 2018

Cellular senescence is identified by a living cell in irreversible and persistent cycle arrest response to various cellular stresses. Senescent cells secrete senescence-associated secretory phenotype factors that can amplify alter the microenvironments. Radiotherapy, via ionizing radiation, serves as an effective treatment for local tumor control with side effects on normal cells, which induce inflammation fibrosis irradiated nearby regions. Research has revealed senescent observable organs. This process starts DNA damage from high or low radiation doses, after G2 occurs virtually all eukaryotic mitotic bypass possibly necessary ultimately establish senescence. Within this complex signaling network, ataxia telangiectasia–mutated protein (ATM), p53, p21 stand out crucial mediators. Senolytic agents, class of small molecules selectively kill hold great potential substantially reduce caused radiotherapy while reasonably steer clear carcinogenesis, improve organic health quality life cancer patients.

Язык: Английский

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