Cellular rejuvenation: molecular mechanisms and potential therapeutic interventions for diseases

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: March 14, 2023

Abstract The ageing process is a systemic decline from cellular dysfunction to organ degeneration, with more predisposition deteriorated disorders. Rejuvenation refers giving aged cells or organisms youthful characteristics through various techniques, such as reprogramming and epigenetic regulation. great leaps in rejuvenation prove that not one-way street, many rejuvenative interventions have emerged delay even reverse the process. Defining mechanism by which roadblocks signaling inputs influence complex programs essential for understanding developing strategies. Here, we discuss intrinsic extrinsic factors counteract cell rejuvenation, targeted core mechanisms involved this Then, critically summarize latest advances state-of-art strategies of rejuvenation. Various methods also provide insights treating specific ageing-related diseases, including reprogramming, removal senescence (SCs) suppression senescence-associated secretory phenotype (SASP), metabolic manipulation, stem cells-associated therapy, dietary restriction, immune heterochronic transplantation, etc. potential applications therapy extend cancer treatment. Finally, analyze detail therapeutic opportunities challenges technology. Deciphering will further into anti-ageing disease treatment clinical settings.

Language: Английский

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AMPK and NRF2: Interactive players in the same team for cellular homeostasis?

Free Radical Biology and Medicine, Journal Year: 2022, Volume and Issue: 190, P. 75 - 93

Published: July 31, 2022

NRF2 (Nuclear factor E2 p45‐related 2) is a stress responsive transcription lending cells resilience against oxidative, xenobiotic, and also nutrient or proteotoxic insults. AMPK (AMP-activated kinase), considered as prime regulator of cellular energy homeostasis, not only tunes metabolism to provide the cell at any time with sufficient ATP building blocks, but controls redox balance inflammation. Due observed overlapping responses upon activation common stressors impinging on both signaling, it plausible assume that signaling may interdepend cooperate readjust homeostasis. After short introduction two players this narrative review paints current picture how might interact molecular level, highlights their possible crosstalk in selected examples pathophysiology bioactivity drugs phytochemicals.

Language: Английский

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AMP-activated protein kinase: An energy sensor and survival mechanism in the reinstatement of metabolic homeostasis

Experimental Cell Research, Journal Year: 2023, Volume and Issue: 428(1), P. 113614 - 113614

Published: April 29, 2023

Language: Английский

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The role of AMPK in macrophage metabolism, function and polarisation

Journal of Translational Medicine, Journal Year: 2023, Volume and Issue: 21(1)

Published: Dec. 8, 2023

AMP-activated protein kinase (AMPK) is a ubiquitous sensor of energy and nutritional status in eukaryotic cells. It plays key role regulating cellular homeostasis multiple aspects cell metabolism. During macrophage polarisation, AMPK not only guides the metabolic programming macrophages, but also counter-regulates inflammatory function macrophages promotes their polarisation toward anti-inflammatory phenotype. located at intersection metabolism inflammation. The characteristics are closely related to immune-related diseases, infectious cancer progression immunotherapy. This review discusses structure its metabolism, macrophages. In addition, it summarises important pathway activators development macrophage-related diseases.

Language: Английский

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Phytochemicals targeting Alzheimer's disease via the AMP-activated protein kinase pathway, effects, and mechanisms of action

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 173, P. 116373 - 116373

Published: March 4, 2024

Alzheimer's disease (AD), characterized by cognitive dysfunction and other behavioral abnormalities, is a progressive neurodegenerative that occurs due to aging. Currently, effective drugs mitigate or treat AD remain unavailable. associated with several abnormalities in neuronal energy metabolism, such as decreased glucose uptake, mitochondrial dysfunction, defects cholesterol metabolism. Amp-activated protein kinase (AMPK) an important serine/threonine regulates the status of cells. AMPK widely present eukaryotic cells can sense regulate metabolism maintain supply demand balance, making it promising target for metabolism-based therapy. Therefore, this review aimed discuss molecular mechanism pathogenesis provide theoretical basis development new anti-AD drugs. To mechanisms phytochemicals treatment via pathway regulation, we searched PubMed, Google Scholar, Web Science, Embase databases using specific keywords related September 2023. Phytochemicals activate exert therapeutic effects AD. The these include inhibiting Aβ aggregation, preventing Tau hyperphosphorylation, inflammatory response glial activation, promoting autophagy, suppressing anti-oxidative stress. Additionally, AMPK-related pathways are involved mechanism, including AMPK/CaMKKβ/mTOR, AMPK/SIRT1/PGC-1α, AMPK/NF-κB/NLRP3, AMPK/mTOR, PERK/eIF2α pathways. Notably, urolithin A, artemisinin, justicidin berberine, stigmasterol, arctigenin, rutaecarpine agonists effects. Several may have potential applications treatment. Overall, phytochemical-based overcome barriers diseases.

Language: Английский

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SIRT1 and Autophagy: Implications in Endocrine Disorders

Frontiers in Endocrinology, Journal Year: 2022, Volume and Issue: 13

Published: July 14, 2022

Autophagy is a cellular process involved in the selective degradation and recycling of dysfunctional intracellular components. It plays crucial role maintaining homeostasis survival by removing damaged harmful proteins, lipids, organelles. SIRT1, an NAD+-dependent multifunctional enzyme, key regulator autophagy process. Through its deacetylase activity, SIRT1 participates regulation different steps autophagy, from initiation to degradation. The levels function are also regulated Dysregulation SIRT1-mediated hinders proper functioning endocrine system, contributing onset progression disorders. This review provides overview crosstalk between their implications obesity, type-2 diabetes mellitus, diabetic cardiomyopathy, hepatic steatosis.

Language: Английский

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Aging, cell senescence, the pathogenesis and targeted therapies of intervertebral disc degeneration

Frontiers in Pharmacology, Journal Year: 2023, Volume and Issue: 14

Published: May 5, 2023

Intervertebral disc degeneration (IVDD) refers to the aging and degenerative diseases of intervertebral components such as nucleus pulposus, annulus fibrosus, cartilage endplate, is main cause chronic low back pain. Over past few years, many researchers around world concerned that pulposus (NP) cells plays role in IVDD. The NP caused by a series pathological processes, including oxidative stress, inflammatory response, apoptosis, abnormal proliferation, autophagy. Interestingly, studies have found close relationship between senescence progression degeneration. classical pathways also been confirmed be involved process Moreover, several anti-aging drugs used treat IVDD inhibiting senescence, proanthocyanidins, resveratrol bone morphogenetic protein 2. Therefore, this article will systematically list discuss aging, cell pathogenesis targeted therapies IVDD, order provide new ideas for treatment future.

Language: Английский

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Ceramides and ceramide synthases in cancer: Focus on apoptosis and autophagy

European Journal of Cell Biology, Journal Year: 2023, Volume and Issue: 102(3), P. 151337 - 151337

Published: June 26, 2023

Different studies corroborate a role for ceramide synthases and their downstream products, ceramides, in modulation of apoptosis autophagy the context cancer. These mechanisms regulation, however, appear to be dependent terms ceramides' fatty acid chain length, subcellular localization, presence or absence targets. Our current understanding ceramides regulation could harnessed pioneer development new treatments activate inhibit single type synthase, thereby regulating induction cross talk cancer cells. Moreover, apoptotic function suggests that analogues can pave way novel treatments. Therefore, review paper we discuss impact different types cancers. We also briefly introduce latest information on synthase inhibitors, application diseases including therapy, approaches drug discovery field inhibitors. finally discussed strategies developing use lipids analysis biological fluids early biomarkers

Language: Английский

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Magnolol improves Alzheimer's disease-like pathologies and cognitive decline by promoting autophagy through activation of the AMPK/mTOR/ULK1 pathway

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 161, P. 114473 - 114473

Published: March 6, 2023

Alzheimer's disease (AD) is the most common neurodegenerative disease. Amyloid-β (Aβ) plaque deposition and apoptosis are main pathological features of AD. Autophagy plays an important role in clearing abnormal protein accumulation inhibiting apoptosis; however, autophagy defects often occur from early stages The serine/threonine AMP-activated kinase (AMPK)/mammalian target rapamycin (mTOR)/unc-51-like 1/2 (ULK1/2) pathway serves as energy sensor involved activation. Furthermore, magnolol regulator, has potential for AD therapy. We propose that can ameliorate pathologies inhibit by regulating through AMPK/mTOR/ULK1 pathway. examined cognitive function AD-related transgenic mice protective mechanism western blotting, flow cytometry, a tandem mRFP-GFP-LC3 adenovirus assay Aβ oligomer (AβO)-induced N2a BV2 cell models. In our study, decreased amyloid pathology ameliorated impairment APP/PS1 mice. Moreover, inhibited downregulating cleaved-caspase-9 Bax upregulating Bcl-2 AβO-induced Magnolol promoted degrading p62/SQSTM1, LC3II Beclin-1 expression. activated increasing phosphorylation AMPK ULK1 decreasing mTOR vivo vitro inhibitor weakened effects promoting apoptosis, knockdown effect on apoptosis. These results indicate inhibits improves activation

Language: Английский

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New Dawn for Atherosclerosis: Vascular Endothelial Cell Senescence and Death

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(20), P. 15160 - 15160

Published: Oct. 13, 2023

Endothelial cells (ECs) form the inner linings of blood vessels, and are directly exposed to endogenous hazard signals metabolites in circulatory system. The senescence death ECs not only adverse outcomes, but also causal contributors endothelial dysfunction, an early risk marker atherosclerosis. pathophysiological process EC involves both structural functional changes has been linked various factors, including oxidative stress, dysregulated cell cycle, hyperuricemia, vascular inflammation, aberrant metabolite sensing signaling. Multiple forms have documented atherosclerosis, autophagic death, apoptosis, pyroptosis, NETosis, necroptosis, ferroptosis. Despite this, molecular mechanisms underlying or atherogenesis fully understood. To provide a comprehensive update on subject, this review examines historic latest findings alterations associated with different stages

Language: Английский

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