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

Relationships among smoking, oxidative stress, inflammation, macromolecular damage, and cancer DOI
Andrew W. Caliri, Stella Tommasi, Ahmad Besaratinia

et al.

Mutation Research/Reviews in Mutation Research, Journal Year: 2021, Volume and Issue: 787, P. 108365 - 108365

Published: Jan. 1, 2021

Language: Английский

Citations

405

Immunosenescence: molecular mechanisms and diseases DOI Creative Commons

Zaoqu Liu,

Qimeng Liang,

Yuqing Ren

et al.

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

Published: May 13, 2023

Abstract Infection susceptibility, poor vaccination efficacy, age-related disease onset, and neoplasms are linked to innate adaptive immune dysfunction that accompanies aging (known as immunosenescence). During aging, organisms tend develop a characteristic inflammatory state expresses high levels of pro-inflammatory markers, termed inflammaging. This chronic inflammation is typical phenomenon immunosenescence it considered the major risk factor for diseases. Thymic involution, naïve/memory cell ratio imbalance, dysregulated metabolism, epigenetic alterations striking features immunosenescence. Disturbed T-cell pools antigen stimulation mediate premature senescence cells, senescent cells proinflammatory senescence-associated secretory phenotype exacerbates Although underlying molecular mechanisms remain be addressed, well documented T inflammaging might driving forces in Potential counteractive measures will discussed, including intervention cellular metabolic-epigenetic axes mitigate In recent years, has attracted increasing attention its role tumor development. As result limited participation elderly patients, impact on cancer immunotherapy unclear. Despite some surprising results from clinical trials drugs, necessary investigate other

Language: Английский

Citations

325

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

Sex differences in biological aging with a focus on human studies DOI Creative Commons
Sara Hägg, Juulia Jylhävä

eLife, Journal Year: 2021, Volume and Issue: 10

Published: May 13, 2021

Aging is a complex biological process characterized by hallmark features accumulating over the life course, shaping individual's aging trajectory and subsequent disease risks. There substantial individual variability in between men women. In general, women live longer than men, consistent with lower ages as assessed molecular biomarkers, but there paradox. Women are frailer have worse health at end of life, while still perform better physical function examinations. Moreover, many age-related diseases show sex-specific patterns. this review, we aim to summarize current knowledge on sexual dimorphism human studies, support from animal research, illnesses. We also attempt place it context theories aging, well discuss explanations for sex differences, example, sex-chromosome linked mechanisms hormonally driven differences.

Language: Английский

Citations

298

Long-term maturation of human cortical organoids matches key early postnatal transitions DOI
Aaron Gordon, Se‐Jin Yoon,

Stephen Tran

et al.

Nature Neuroscience, Journal Year: 2021, Volume and Issue: 24(3), P. 331 - 342

Published: Feb. 22, 2021

Language: Английский

Citations

276

Caloric Restriction Reprograms the Single-Cell Transcriptional Landscape of Rattus Norvegicus Aging DOI Creative Commons
Shuai Ma, Shuhui Sun,

Lingling Geng

et al.

Cell, Journal Year: 2020, Volume and Issue: 180(5), P. 984 - 1001.e22

Published: Feb. 27, 2020

Language: Английский

Citations

274

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

Inflammation, epigenetics, and metabolism converge to cell senescence and ageing: the regulation and intervention DOI Creative Commons
Xudong Zhu, Zhiyang Chen,

Weiyan Shen

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2021, Volume and Issue: 6(1)

Published: June 28, 2021

Remarkable progress in ageing research has been achieved over the past decades. General perceptions and experimental evidence pinpoint that decline of physical function often initiates by cell senescence organ ageing. Epigenetic dynamics immunometabolic reprogramming link to alterations cellular response intrinsic extrinsic stimuli, representing current hotspots as they not only (re-)shape individual identity, but also involve fate decision. This review focuses on present findings emerging concepts epigenetic, inflammatory, metabolic regulations consequences process. Potential therapeutic interventions targeting regulatory mechanisms, using state-of-the-art techniques are discussed.

Language: Английский

Citations

228

Aging Atlas: a multi-omics database for aging biology DOI Creative Commons
Guang‐Hui Liu, Yīmíng Bào, Jing Qu

et al.

Nucleic Acids Research, Journal Year: 2020, Volume and Issue: 49(D1), P. D825 - D830

Published: Sept. 30, 2020

Organismal aging is driven by interconnected molecular changes encompassing internal and extracellular factors. Combinational analysis of high-throughput 'multi-omics' datasets (gathering information from genomics, epigenomics, transcriptomics, proteomics, metabolomics pharmacogenomics), at either populational or single-cell levels, can provide a multi-dimensional, integrated profile the heterogeneous process with unprecedented throughput detail. These new strategies allow for exploration regulatory status gene expression during aging, in turn, facilitate development interventions. With continually growing volume valuable aging-related data, it necessary to establish an open database support wide spectrum research. The Aging Atlas aims range life science researchers resources that access large-scale regulation created various omics technologies. current implementation includes five modules: transcriptomics (RNA-seq), (scRNA-seq), epigenomics (ChIP-seq), proteomics (protein-protein interaction), pharmacogenomics (geroprotective compounds). provides user-friendly functionalities explore age-related expression, as well raw data download services. freely available https://bigd.big.ac.cn/aging/index.

Language: Английский

Citations

219

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