SGF29 nuclear condensates reinforce cellular aging DOI Creative Commons
Kaowen Yan, Qianzhao Ji, Dongxin Zhao

et al.

Cell Discovery, Journal Year: 2023, Volume and Issue: 9(1)

Published: Nov. 7, 2023

Phase separation, a biophysical segregation of subcellular milieus referred as condensates, is known to regulate transcription, but its impacts on physiological processes are less clear. Here, we demonstrate the formation liquid-like nuclear condensates by SGF29, component SAGA transcriptional coactivator complex, during cellular senescence in human mesenchymal progenitor cells (hMPCs) and fibroblasts. The Arg 207 within intrinsically disordered region identified key amino acid residue for SGF29 form phase separation. Through epigenomic transcriptomic analysis, our data indicated that both condensate H3K4me3 binding essential establishing precise chromatin location, recruiting factors co-activators target specific genomic loci, initiating expression genes associated with senescence, such CDKN1A. alone, however, may not be sufficient drive or achieve transactivation functions. Our study establishes link between separation aging regulation, highlighting functional unit facilitate shaping landscapes aging.

Language: Английский

Aging and aging-related diseases: from molecular mechanisms to interventions and treatments DOI Creative Commons
Jun Guo, Xiuqing Huang, Lin Dou

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: Dec. 16, 2022

Aging is a gradual and irreversible pathophysiological process. It presents with declines in tissue cell functions significant increases the risks of various aging-related diseases, including neurodegenerative cardiovascular metabolic musculoskeletal immune system diseases. Although development modern medicine has promoted human health greatly extended life expectancy, aging society, variety chronic diseases have gradually become most important causes disability death elderly individuals. Current research on focuses elucidating how endogenous exogenous stresses (such as genomic instability, telomere dysfunction, epigenetic alterations, loss proteostasis, compromise autophagy, mitochondrial cellular senescence, stem exhaustion, altered intercellular communication, deregulated nutrient sensing) participate regulation aging. Furthermore, thorough pathogenesis to identify interventions that promote longevity caloric restriction, microbiota transplantation, nutritional intervention) clinical treatment methods for (depletion senescent cells, therapy, antioxidative anti-inflammatory treatments, hormone replacement therapy) could decrease incidence turn healthy longevity.

Language: Английский

Citations

728
Epigenetic regulation of aging: implications for interventions of aging and diseases DOI Creative Commons
Wang Kang, Huicong Liu, Qinchao Hu

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: Nov. 7, 2022

Abstract Aging is accompanied by the decline of organismal functions and a series prominent hallmarks, including genetic epigenetic alterations. These aging-associated changes include DNA methylation, histone modification, chromatin remodeling, non-coding RNA (ncRNA) regulation, all which participate in regulation aging process, hence contribute to aging-related diseases. Therefore, understanding mechanisms will provide new avenues develop strategies delay aging. Indeed, interventions based on manipulating have led alleviation or extension lifespan animal models. Small molecule-based therapies reprogramming that enable rejuvenation been developed for ameliorating reversing conditions. In addition, adopting health-promoting activities, such as caloric restriction, exercise, calibrating circadian rhythm, has demonstrated Furthermore, various clinical trials intervention are ongoing, providing more evidence safety efficacy these therapies. Here, we review recent work outline advances age-associated A better critical roles epigenetics process lead prevention human therapy

Language: Английский

Citations

307
The landscape of aging DOI Open Access
Yusheng Cai, Wei Song, Jiaming Li

et al.

Science China Life Sciences, Journal Year: 2022, Volume and Issue: 65(12), P. 2354 - 2454

Published: Sept. 2, 2022

Language: Английский

Citations

243
Resurrection of endogenous retroviruses during aging reinforces senescence DOI Creative Commons
Xiaoqian Liu, Zunpeng Liu, Zeming Wu

et al.

Cell, Journal Year: 2023, Volume and Issue: 186(2), P. 287 - 304.e26

Published: Jan. 1, 2023

Whether and how certain transposable elements with viral origins, such as endogenous retroviruses (ERVs) dormant in our genomes, can become awakened contribute to the aging process is largely unknown. In human senescent cells, we found that HERVK (HML-2), most recently integrated ERVs, are unlocked transcribe genes produce retrovirus-like particles (RVLPs). These RVLPs constitute a transmissible message elicit senescence phenotypes young which be blocked by neutralizing antibodies. The activation of ERVs was also observed organs aged primates mice well tissues serum from elderly. Their repression alleviates cellular tissue degeneration and, some extent, organismal aging. findings indicate resurrection hallmark driving force

Language: Английский

Citations

211
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

197
Epigenomic dissection of Alzheimer’s disease pinpoints causal variants and reveals epigenome erosion DOI Creative Commons
Xushen Xiong, Benjamin T. James, Carles A. Boix

et al.

Cell, Journal Year: 2023, Volume and Issue: 186(20), P. 4422 - 4437.e21

Published: Sept. 1, 2023

Recent work has identified dozens of non-coding loci for Alzheimer's disease (AD) risk, but their mechanisms and AD transcriptional regulatory circuitry are poorly understood. Here, we profile epigenomic transcriptomic landscapes 850,000 nuclei from prefrontal cortexes 92 individuals with without to build a map the brain regulome, including profiles, regulators, co-accessibility modules, peak-to-gene links in cell-type-specific manner. We develop methods multimodal integration detecting modules using linking. show risk enriched microglial enhancers specific TFs SPI1, ELF2, RUNX1. detect 9,628 ATAC-QTL loci, which integrate alongside prioritize variant circuits. report differential accessibility late glia early neurons. Strikingly, late-stage brains global epigenome dysregulation indicative erosion cell identity loss.

Language: Английский

Citations

93
SenNet recommendations for detecting senescent cells in different tissues DOI
Vidyani Suryadevara, Adam D. Hudgins,

Adarsh Rajesh

et al.

Nature Reviews Molecular Cell Biology, Journal Year: 2024, Volume and Issue: 25(12), P. 1001 - 1023

Published: June 3, 2024

Language: Английский

Citations

89
Methylation across the central dogma in health and diseases: new therapeutic strategies DOI Creative Commons
Ruochen Liu, Erhu Zhao,

Huijuan Yu

et al.

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

Published: Aug. 24, 2023

The proper transfer of genetic information from DNA to RNA protein is essential for cell-fate control, development, and health. Methylation DNA, RNAs, histones, non-histone proteins a reversible post-synthesis modification that finetunes gene expression function in diverse physiological processes. Aberrant methylation caused by mutations or environmental stimuli promotes various diseases accelerates aging, necessitating the development therapies correct disease-driver imbalance. In this Review, we summarize operating system across central dogma, which includes writers, erasers, readers, reader-independent outputs. We then discuss how dysregulation contributes neurological disorders, cancer, aging. Current small-molecule compounds target modifiers show modest success certain cancers. methylome-wide action lack specificity lead undesirable biological effects cytotoxicity, limiting their therapeutic application, especially with monogenic cause different directions changes. Emerging tools capable site-specific manipulation hold great promise solve dilemma. With refinement delivery vehicles, these new are well positioned advance basic research clinical translation field.

Language: Английский

Citations

56
Stress, epigenetics, and aging: Unraveling the intricate crosstalk DOI Creative Commons
Zeming Wu, Jing Qu, Weiqi Zhang

et al.

Molecular Cell, Journal Year: 2023, Volume and Issue: 84(1), P. 34 - 54

Published: Nov. 13, 2023

Language: Английский

Citations

54
The hallmarks of aging as a conceptual framework for health and longevity research DOI Creative Commons
Antonio G. Tartiere, José M.P. Freije, Carlos López-Otı́n

et al.

Frontiers in Aging, Journal Year: 2024, Volume and Issue: 5

Published: Jan. 15, 2024

The inexorability of the aging process has sparked curiosity human beings since ancient times. However, despite this interest and extraordinary scientific advances in field, complexity hampered its comprehension. In context, Hallmarks Aging were defined 2013 with aim establishing an organized, systematic integrative view topic, which would serve as a conceptual framework for research. Ten years later promoted by progress area, updated version included three new hallmarks while maintaining original scope. review is to determine what extent achieved purpose that gave rise them. For aim, we have reviewed literature citing any two versions conclude they served not only research but also related areas knowledge. Finally, discusses candidates become part list, analyzing evidence supports whether should or be incorporated.

Language: Английский

Citations

22