Inflammatory, mitochondrial, and senescence-related markers: Underlying biological pathways of muscle aging and new therapeutic targets DOI Creative Commons
Anna Picca, Biliana Lozanoska‐Ochser, Riccardo Calvani

et al.

Experimental Gerontology, Journal Year: 2023, Volume and Issue: 178, P. 112204 - 112204

Published: May 18, 2023

The maintenance of functional health is pivotal for achieving independent life in older age. aged muscle characterized by ultrastructural changes, including loss type I and II myofibers a greater proportion cytochrome c oxidase deficient succinate dehydrogenase positive fibers. Both intrinsic (e.g., altered proteostasis, DNA damage, mitochondrial dysfunction) extrinsic factors denervation, metabolic regulation, declines satellite cells, inflammation) contribute to aging. Being hub several cellular activities, mitochondria are key myocyte viability dysfunction has been implicated age-associated physical decline. organelles via quality control (MQC) processes is, therefore, crucial skeletal myofiber organismal health. autophagy-lysosome pathway emerged as critical step MQC disposing proteins their tagging autophagosome incorporation delivery the lysosome clearance. This was found be physically inactive adults. A relationship between this tissue composition lower extremities well performance also identified. Therefore, integrating structure measures evaluation may promising strategy devising interventions fostering

Language: Английский

Control of satellite cell function in muscle regeneration and its disruption in ageing DOI
Pedro Sousa‐Victor, Laura García‐Prat, Pura Muñoz‐Cánoves

et al.

Nature Reviews Molecular Cell Biology, Journal Year: 2021, Volume and Issue: 23(3), P. 204 - 226

Published: Oct. 18, 2021

Language: Английский

Citations

288

Ageing and rejuvenation of tissue stem cells and their niches DOI
Anne Brunet, Margaret A. Goodell, Thomas A. Rando

et al.

Nature Reviews Molecular Cell Biology, Journal Year: 2022, Volume and Issue: 24(1), P. 45 - 62

Published: July 20, 2022

Language: Английский

Citations

222

Biomarkers of aging DOI Open Access

Hainan Bao,

Jiani Cao, Mengting Chen

et al.

Science China Life Sciences, Journal Year: 2023, Volume and Issue: 66(5), P. 893 - 1066

Published: April 11, 2023

Language: Английский

Citations

203

Cellular rejuvenation: molecular mechanisms and potential therapeutic interventions for diseases DOI Creative Commons

Shuaifei Ji,

Mingchen Xiong,

Huating Chen

et al.

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

Citations

82

Fiber-Type Shifting in Sarcopenia of Old Age: Proteomic Profiling of the Contractile Apparatus of Skeletal Muscles DOI Open Access
Paul Dowling, Stephen Gargan, Dieter Swandulla

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(3), P. 2415 - 2415

Published: Jan. 26, 2023

The progressive loss of skeletal muscle mass and concomitant reduction in contractile strength plays a central role frailty syndrome. Age-related neuronal impairments are closely associated with sarcopenia the elderly, which is characterized by severe muscular atrophy that can considerably lessen overall quality life at old age. Mass-spectrometry-based proteomic surveys senescent human muscles, as well animal models sarcopenia, have decisively improved our understanding molecular cellular consequences fiber-type shifting during aging. This review outlines spectrometric identification proteome-wide changes atrophying focus on proteins potential markers distribution patterns. observed trend fast-to-slow transitions individual muscles aging process most likely linked to preferential susceptibility fast-twitching fibers atrophy. Studies models, including mostly aged rodent confirmed shifting. analysis fast versus slow isoforms key proteins, such myosin heavy chains, light actins, troponins tropomyosins, suggests them suitable bioanalytical tools

Language: Английский

Citations

48

Exercise reprograms the inflammatory landscape of multiple stem cell compartments during mammalian aging DOI
Ling Liu, Soochi Kim,

Matthew T. Buckley

et al.

Cell stem cell, Journal Year: 2023, Volume and Issue: 30(5), P. 689 - 705.e4

Published: April 19, 2023

Language: Английский

Citations

44

Circulating tumor cells: from new biological insights to clinical practice DOI Creative Commons
Xuyu Gu, Shiyou Wei,

Xin Lv

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Sept. 2, 2024

Abstract The primary reason for high mortality rates among cancer patients is metastasis, where tumor cells migrate through the bloodstream from original site to other parts of body. Recent advancements in technology have significantly enhanced our comprehension mechanisms behind bloodborne spread circulating (CTCs). One critical process, DNA methylation, regulates gene expression and chromosome stability, thus maintaining dynamic equilibrium Global hypomethylation locus-specific hypermethylation are examples changes methylation patterns that pivotal carcinogenesis. This comprehensive review first provides an overview various processes contribute formation CTCs, including epithelial-mesenchymal transition (EMT), immune surveillance, colonization. We then conduct in-depth analysis how modifications within CTCs impact each these stages during CTC dissemination. Furthermore, we explored potential clinical implications with cancer. By understanding epigenetic modifications, can gain insights into metastatic process identify new biomarkers early detection, prognosis, targeted therapies. aims bridge gap between basic research application, highlighting significance context metastasis offering avenues improving patient outcomes.

Language: Английский

Citations

32

Longevity interventions modulate mechanotransduction and extracellular matrix homeostasis in C. elegans DOI Creative Commons
Alina C. Teuscher, Cyril Statzer, Anita Goyala

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Jan. 4, 2024

Abstract Dysfunctional extracellular matrices (ECM) contribute to aging and disease. Repairing dysfunctional ECM could potentially prevent age-related pathologies. Interventions promoting longevity also impact gene expression. However, the role of composition changes in healthy remains unclear. Here we perform proteomics in-vivo monitoring systematically investigate (matreotype) during C. elegans revealing three distinct collagen dynamics. Longevity interventions slow stiffening prolong expression collagens that are turned over. These prolonged dynamics mediated by a mechanical feedback loop hemidesmosome-containing structures span from exoskeletal through hypodermis, basement membrane ECM, muscles, coupling forces adjust via transcriptional co-activator YAP-1 across tissues. Our results provide evidence coordinated remodeling mechanotransduction is required sufficient promote longevity, offering potential avenues for targeting

Language: Английский

Citations

20

Cellular reprogramming as a tool to model human aging in a dish DOI Creative Commons
Patrícia R. Pitrez, Luís Miguel Monteiro,

Oliver Borgogno

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Feb. 28, 2024

Abstract The design of human model systems is highly relevant to unveil the underlying mechanisms aging and provide insights on potential interventions extend health life span. In this perspective, we explore 2D or 3D culture models comprising induced pluripotent stem cells transdifferentiated obtained from aged age-related disorder-affected donors enhance our understanding catalyze discovery anti-aging interventions.

Language: Английский

Citations

18

Ageing induces tissue‐specific transcriptomic changes in Caenorhabditis elegans DOI Creative Commons
Xueqing Wang, Quanlong Jiang, Yuanyuan Song

et al.

The EMBO Journal, Journal Year: 2022, Volume and Issue: 41(8)

Published: March 7, 2022

Resource7 March 2022Open Access Transparent process Ageing induces tissue-specific transcriptomic changes in Caenorhabditis elegans Xueqing Wang orcid.org/0000-0003-3136-2568 State Key Laboratory of Cell Biology, Shanghai Institute Biochemistry and Center for Excellence Molecular Science, Chinese Academy Sciences, Shanghai, China University Beijing, Contribution: Resources, Data curation, Formal analysis, Validation, ​Investigation, Visualization, Methodology, Writing - original draft, review & editing Search more papers by this author Quanlong Jiang CAS Computational Nutrition Health, Institutes Biological Peking-Tsinghua Life Advanced Interdisciplinary Studies, Quantitative Biology (CQB), Peking University, Software, Yuanyuan Song ​Investigation Zhidong He Hongdao Zhang orcid.org/0000-0003-2390-0450 Mengjiao Visualization Xiaona orcid.org/0000-0001-6479-3562 Yumin Dai Oezlem Karalay Max Planck Ageing, Cologne, Germany Cologne Cluster on Cellular Stress Responses Aging-Associated Diseases (CECAD), Christoph Dieterich Klaus Tschira Integrative Cardiology Department Internal Medicine III, Hospital Heidelberg, Adam Antebi Supervision, draft Ligang Wu Corresponding Author [email protected] orcid.org/0000-0003-4010-9118 Funding acquisition, Project administration Jing-Dong J Han orcid.org/0000-0002-9270-7139 Yidong Shen orcid.org/0000-0002-2841-7233 Conceptualization, administration, Information Wang1,2,†, Jiang3,4,†, Song1,2,†, He1,2, Zhang1,2, Song1,2, Dai1,2, Karalay5,6, Dieterich7, Antebi5,6, *,1,2, *,3,4 *,1,2 1State 2University 3CAS 4Peking-Tsinghua 5Max 6Cologne 7Klaus † These authors contributed equally to work *Corresponding author. Tel: +86 21 54921321; E-mail: 10 62757330; 54921171; The EMBO Journal (2022)41:e109633https://doi.org/10.15252/embj.2021109633 PDFDownload PDF article text main figures. Peer ReviewDownload a summary the editorial decision including letters, reviewer comments responses feedback. ToolsAdd favoritesDownload CitationsTrack CitationsPermissions Figures Info Abstract is complex with common distinct features across tissues. Unveiling underlying processes driving ageing individual tissues indispensable decipher mechanisms organismal longevity. well-established model organism that has spearheaded research discovery numerous genetic pathways controlling its lifespan. However, it remains challenging dissect worm due limited description tissue pathology access molecular during ageing. In study, we isolated cells from five major young old worms profiled age-induced within these We observed striking diversity identified different sets longevity regulators therein. addition, found novel factors, irx-1 myrf-2, which control integrity intestinal barrier sarcomere structure respectively. This study demonstrates complexity highlights power profiling ageing, can serve as resource field. Synopsis Whether associated specific organs poorly addressed. Here, dissection analyses diverse C. provides insight into disting trajectories each them. Five somatic tissues—nervous system, hypodermis, intestine, coelomocyte body all muscle undergo Tissue-specific between are pronounced than regulates similar biological gene Transcription factors irx-1/IRX myrf-2/MYRF intestine wall muscle, Introduction causes systematic decline physiological functions therefore poses risk various severe diseases aged population (Campisi et al, 2019). Over past decades, cellular systems protect have been substantially charted pioneering studies organisms (Kenyon, 2010; Riera 2016; Campisi nematode among foremost models research, short lifespan only few weeks, but displaying phenotypes humans (Mack 2018). It was first shown regulated evolutionarily conserved signalling identification insulin/IGF-1 (IIS) pathway (Johnson, 1990; Kenyon 1993; Morris 1996; Ogg 1997; Kenyon, 2011). Mutations critical IIS genes, such FOXO3A, were later be human (Willcox 2008). Since then, also pioneered other milestone findings biology Mack 2018; or interventions induce evident (Lund 2002; McElwee 2003; Murphy Hou Li proposed represent (Murphy 2003). transcriptional information previous mainly whole animals ages mutants technical difficulty dissecting interest tiny (Corsi 2015). datasets provided key insights researchers using well organisms. Nevertheless, cannot solely analysed at level animal, since characteristic trajectory, driven unique (Rando Wyss-Coray, 2021). tissue–tissue communication plays an essential role systemic level, how occurs relationship remain elusive. order autonomous non-autonomous multicellular organisms, profile Yet, lack age-related significant gap our understanding. By improving protocol isolate embryonic neurons fluorescence-activated cell sorting (FACS) (Von Stetina 2007), lab GFP-labelled cells, enabling adult (Kaletsky 2016, Following their technique, further developed method micromanipulation (Zhou current (i.e. neuron, hypodermis coelomocytes) thereby From perspective differentially expressed regulators, results indicate remarkable not arise structures regulations same atlas tissues, two transcription myrf-2 deterioration sarcomere. provide foundation explore machinery Results Sequencing To transcriptomes labelled fluorescent markers dissociated. (BWM), identities hand-picked Neurons composed classes collected FACS 2016). day 1 adulthood (D1) considered young, whereas post-reproductive 8 (D8) aged. both subjected Smart-seq2 (Picelli 2013) (Fig 1A). viability validated indicators (Zhang 2011) EV1A). A battery genes examined qRT–PCR assess purity samples EV1B). type manually picked BWM, coelomocytes, expression corresponding detected, EV1C–F), indicating largely devoid contamination. With reports 2018), FACS-isolated neuron highly enriched EV1G). Figure 1. Worm A. flowchart depicting Isolated pooled Smart-seq2. B, Principal component analysis (B) hierarchical clustering (C) three replicates. D1: adulthood, D8: adulthood. Neu: Int: BWM: Hyp: Coel: coelomocyte. D. volcano plots showing Genes fold change > 1.5 P-value smaller 0.05 significantly changed numbers percentages Age-DEGs plots. Download figure PowerPoint Click here expand figure. EV1. validation assay cells. Cells neurons, GFP reporters. Dead preparations (RFP) ethidium homodimer-1 staining (RFP). preparation coelomocytes live RFP Calcein AM (GFP) Arrow heads denote interest. Scale bar: 20 µm. B. list used. C–F. RT–qPCR indicated (C), (D), (E) (F). ND: Ct 40. Mean ± SD. n = 3 G. (left) RNA-Seq reads (right) comparable previously reported. Unpaired t-test, two-tailed. As expected, underwent (Figs 1B–D EV2A). showed sequenced clustered types then 1B C), highlighting distinctive reported 2018) effects expression. When compared D1 counterparts, 3,744, 2,246, 1,189, 902 1,056 D8 respectively 1D Dataset EV1). ageing-regulated (Age-DEGs) comprise 21.5, 18.4, 7.4, 11.5 7.7% 1D) 50.1% orthologs mammals EV2B EV1), share EV2. heatmap conserved. comparison Different exhibit deteriorate whether ageing-induced other, those D7. Only small fraction tested altered 2A B EV3C). dataset D2 (Hou 2016) EV3A, D). Therefore, could signature 2. variable A, overlap upregulated (A) downregulated number ratio Venn diagrams. Hypergeometric test. drops increase X-axis denotes EV3. report al (2016), comparing WT 2 C, samples. (C): data obtained (Worm). (D): (2016). (Worm (H)). Red lines pursue hypothesis, speculated, substantial EV2C EV3C 82.8, 72.7, 61.7, 65.7 74.1% 2C EV2C). ratios 74.1, 69.3, 67.2, 59.3 57.6%, respectively, patterns necessarily restricted because most express (Appendix Fig S1A–F). regulate differently high specificities Age-DEGs, exhibited decrease 2D). surprisingly there no shared D, unlikely alter core group Taken together, specificity changes. portray next used WormCat, powerful tool analysing multiple datasets, examine functional (Holdorf 2020). WormCat categorises function (Category 1) location (Categories 3) Category 1, many (Age-BPs) worm. 74.2% 73.9% Age-BPs least 3A EV2). Among them some well-known hallmarks, stress response metabolism (Lopez-Otin 2013). Interestingly, up- implying impact 3. WormCat. Categories differentiated capitalisation bold fonts. below cyan blocks. detailed 3, facets general 2), consistently At 2, 62.0 58.2% Age-BPs, detected one tissue, were, 71.9 64.6% (Dataset Gene ontology (GO) analys

Language: Английский

Citations

45