Exercise metabolism and adaptation in skeletal muscle

Nature Reviews Molecular Cell Biology, Год журнала: 2023, Номер 24(9), С. 607 - 632

Опубликована: Май 24, 2023

Язык: Английский

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Guidelines for minimal information on cellular senescence experimentation in vivo

Cell, Год журнала: 2024, Номер 187(16), С. 4150 - 4175

Опубликована: Авг. 1, 2024

Cellular senescence is a cell fate triggered in response to stress and characterized by stable cell-cycle arrest hypersecretory state. It has diverse biological roles, ranging from tissue repair chronic disease. The development of new tools study vivo paved the way for uncovering its physiological pathological roles testing senescent cells as therapeutic target. However, lack specific broadly applicable markers makes it difficult identify characterize tissues living organisms. To address this, we provide practical guidelines called "minimum information cellular experimentation vivo" (MICSE). presents an overview rodent tissues, transgenic models, non-mammalian systems, human tumors their use identification specification cells. These uniform, state-of-the-art, accessible toolset improve our understanding vivo.

Язык: Английский

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Biomarkers of cellular senescence and risk of death in humans

Aging Cell, Год журнала: 2023, Номер 22(12)

Опубликована: Окт. 6, 2023

Abstract A robust and heterogenous secretory phenotype is a core feature of most senescent cells. In addition to mediators age‐related pathology, components the senescence associated (SASP) have been studied as biomarkers cell burden and, in turn, biological age. Therefore, we hypothesized that circulating concentrations candidate biomarkers, including chemokines, cytokines, matrix remodeling proteins, growth factors, could predict mortality older adults. We assessed associations between plasma levels 28 SASP proteins risk over median follow‐up 6.3 years 1923 patients 65 age or with zero one chronic condition at baseline. Overall, five strongly an increased death were GDF15, RAGE, VEGFA, PARC, MMP2, after adjusting for age, sex, race, presence condition. The combination clinical demographic covariates exhibited significantly higher c‐statistic (0.79, 95% confidence interval (CI): 0.76–0.82) than alone (0.70, CI: 0.67–0.74) ( p < 0.001). Collectively, these findings lend further support cellular informative predictors clinically important health outcomes adults, death.

Язык: Английский

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Cellular senescence in skeletal disease: mechanisms and treatment

Cellular & Molecular Biology Letters, Год журнала: 2023, Номер 28(1)

Опубликована: Окт. 27, 2023

Abstract The musculoskeletal system supports the movement of entire body and provides blood production while acting as an endocrine organ. With aging, balance bone homeostasis is disrupted, leading to loss degenerative diseases, such osteoporosis, osteoarthritis, intervertebral disc degeneration. Skeletal diseases have a profound impact on motor cognitive abilities elderly, thus creating major challenge for both global health economy. Cellular senescence caused by various genotoxic stressors results in permanent cell cycle arrest, which considered be underlying mechanism aging. During senescent cells (SnCs) tend aggregate trigger chronic inflammation releasing senescence-associated secretory phenotypic factors. Multiple signalling pathways are involved regulating cellular marrow microenvironments. Targeted SnCs alleviate age-related diseases. However, association between remains unclear. This review summarises fundamental role skeletal highlights that mediate senescence, discusses potential therapeutic strategies targeting SnCs. Graphical

Язык: Английский

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Calorie restriction reduces biomarkers of cellular senescence in humans

Aging Cell, Год журнала: 2023, Номер 23(2)

Опубликована: Ноя. 14, 2023

Abstract Calorie restriction (CR) with adequate nutrient intake is a potential geroprotective intervention. To advance this concept in humans, we tested the hypothesis that moderate CR healthy young‐to‐middle‐aged individuals would reduce circulating biomarkers of cellular senescence, fundamental mechanism aging and aging‐related conditions. Using plasma specimens from Comprehensive Assessment Long‐term Effects Reducing Intake Energy (CALERIE™) phase 2 study, found significantly reduced concentrations several senescence at 12 24 months compared to an ad libitum diet. machine learning, changes biomarker emerged as important predictors change HOMA‐IR insulin sensitivity index months, resting metabolic rate residual months. Finally, using adipose tissue RNA‐sequencing data subset participants, observed significant reduction senescence‐focused gene set response both baseline. Our results understanding effects humans further support link between health.

Язык: Английский

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Disuse‐induced muscle fibrosis, cellular senescence, and senescence‐associated secretory phenotype in older adults are alleviated during re‐ambulation with metformin pre‐treatment

Aging Cell, Год журнала: 2023, Номер 22(11)

Опубликована: Июль 24, 2023

Abstract Muscle inflammation and fibrosis underlie disuse‐related complications may contribute to impaired muscle recovery in aging. Cellular senescence is an emerging link between inflammation, extracellular matrix (ECM) remodeling poor after disuse. In rodents, metformin has been shown prevent cellular senescence/senescent associated secretory phenotype (SASP), making it a potentially practical therapeutic solution. Thus, the purpose of this study was determine older adults if monotherapy during bed rest could reduce senescence/SASP re‐ambulation period. A two‐arm controlled trial utilized healthy male female ( n = 20; BMI: <30, age: 60 years+) randomized into either placebo or treatment two‐week run‐in 5 days bedrest followed by withdrawal 7 recovery. We found that metformin‐treated individuals had less type‐I myofiber atrophy disuse, reduced pro‐inflammatory transcriptional profiles, lower collagen deposition Collagen content size corresponded whole SASP markers. Moreover, primary resident fibro‐adipogenic progenitors (FAPs) senescent markers promoted shift fibroblast fate be myofibroblast‐like. Together, these results suggest pre‐treatment improved ECM disuse possibly altering skeletal FAPs.

Язык: Английский

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The role of p21 in cellular senescence and aging-related diseases

Molecules and Cells, Год журнала: 2024, Номер unknown, С. 100113 - 100113

Опубликована: Сен. 1, 2024

Язык: Английский

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Biomarkers of Cellular Senescence Predict the Onset of Mobility Disability and Are Reduced by Physical Activity in Older Adults

The Journals of Gerontology Series A, Год журнала: 2023, Номер 79(3)

Опубликована: Ноя. 8, 2023

Abstract Studies in mice and cross-sectional studies humans support the premise that cellular senescence is a contributing mechanism to age-associated deficits physical function. We tested hypotheses circulating proteins secreted by senescent cells are (i) associated with incidence of major mobility disability (MMD), development persistent (PMMD), decrements functioning older adults, (ii) influenced activity (PA). Using samples data obtained longitudinally from Lifestyle Interventions Elders Study clinical trial, we measured panel 27 cells. Among 1 377 women men randomized either structured PA intervention or healthy aging (HA) intervention, observed significant associations between several biomarkers, most distinctly vascular endothelial growth factor A (VEGFA), tumor necrosis receptor (TNFR1), matrix metallopeptidase 7 (MMP7), onset both MMD PMMD. Moreover, VEGFA, GDF15, osteopontin, other biomarkers were reductions short performance battery scores. The change did not differ HA participants. In whole cohort, higher levels significantly greater 10 senescence-related at 12 and/or 24 months. These reinforce as functional decline potential for attenuate this hallmark aging. Clinical Trials Registration Number: NCT01072500

Язык: Английский

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CDKN1A/p21 in Breast Cancer: Part of the Problem, or Part of the Solution?

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(24), С. 17488 - 17488

Опубликована: Дек. 14, 2023

Cyclin-dependent kinase inhibitor 1A (Cip1/Waf1/CDKN1A/p21) is a well-established protein, primarily recognised for its pivotal role in the cell cycle, where it induces cycle arrest by inhibiting activity of cyclin-dependent kinases (CDKs). Over years, extensive research has shed light on various additional mechanisms involving CDKN1A/p21, implicating processes such as apoptosis, DNA damage response (DDR), and regulation stem fate. Interestingly, p21 can function either an oncogene or tumour suppressor these contexts. Complicating matters further, expression CDKN1A/p21 elevated certain types while downregulated others. In this comprehensive review, we provide overview multifaceted functions present clinical data pertaining to cancer patients, delve into potential strategies targeting therapeutic approach cancer. Manipulating shows great promise therapy given involvement multiple hallmarks, sustained proliferation, renewal cells (CSCs), epithelial-mesenchymal transition (EMT), migration, resistance chemotherapy. Given dual processes, more in-depth understanding specific action regulatory network imperative establishing successful interventions.

Язык: Английский

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Cellular Senescence and Inflammaging in the Bone: Pathways, Genetics, Anti-Aging Strategies and Interventions

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(13), С. 7411 - 7411

Опубликована: Июль 5, 2024

Advancing age is associated with several age-related diseases (ARDs), musculoskeletal conditions impacting millions of elderly people worldwide. With orthopedic contributing towards considerable number patients, a deeper understanding bone aging the need hour. One underlying factors cellular senescence and its secretory phenotype (SASP). SASP comprises pro-inflammatory markers, cytokines chemokines that arrest cell growth development. The accumulation over years leads to chronic low-grade inflammation advancing age, also known as inflammaging. pathways molecular mechanisms focused on inflammaging are currently limited but increasingly being explored. Most genes, involved in coincide those cancer other ARDs like osteoarthritis (OA). Thus, exploring these using techniques sequencing, identifying combatting them most suitable approach crucial for healthy early detection ARDs. Several approaches can be used aid regeneration reduce bone. These may pharmacological, non-pharmacological lifestyle interventions. increasing evidence intricate relationship between aging, senescence, ARDs, anti-aging strategies marrow (BM).

Язык: Английский

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