Retrotransposons as a Source of DNA Damage in Neurodegeneration DOI Creative Commons

Eugénie Pezé-Heidsieck,

Tom Bonnifet,

Rania Znaidi

et al.

Frontiers in Aging Neuroscience, Journal Year: 2022, Volume and Issue: 13

Published: Jan. 4, 2022

The etiology of aging-associated neurodegenerative diseases (NDs), such as Parkinson's disease (PD) and Alzheimer's (AD), still remains elusive no curative treatment is available. Age the major risk factor for PD AD, but molecular link between aging neurodegeneration not fully understood. Aging defined by several hallmarks, some which partially overlap with pathways implicated in NDs. Recent evidence suggests that epigenetic alterations can lead to derepression LINE-1 (Long Interspersed Element-1) family transposable elements (TEs) this might have important implications pathogenesis Almost half human DNA composed repetitive sequences derived from TEs TE mobility participated shaping mammalian genomes during evolution. Although most are mutated longer mobile, more than 100 retained their full coding potential humans thus retrotransposition competent. Uncontrolled activation has now been reported various models diseased brain tissues. We will discuss review contribution inducing damage genomic instability, emerging pathological features represent an neurodegeneration, a target urgently needed novel therapeutic disease-modifying interventions.

Language: Английский

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

337
Epigenetics of Aging and Aging-Associated Diseases DOI Open Access
Dominik Saul, Robyn Laura Kosinsky

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(1), P. 401 - 401

Published: Jan. 2, 2021

Aging represents the multifactorial decline in physiological function of every living organism. Over past decades, several hallmarks aging have been defined, including epigenetic deregulation. Indeed, multiple events were found altered across different species during aging. Epigenetic changes directly contributing to and aging-related diseases include accumulation histone variants, chromatin accessibility, loss histones heterochromatin, aberrant modifications, deregulated expression/activity miRNAs. As a consequence, cellular processes are affected, which results development or progression human pathologies, cancer, diabetes, osteoporosis, neurodegenerative disorders. In this review, we focus on mechanisms underlying various describe how these deregulations contribute diseases.

Language: Английский

Citations

171
Senescence and the tumor-immune landscape: Implications for cancer immunotherapy DOI Creative Commons
Loretah Chibaya,

Jarin T. Snyder,

Marcus Ruscetti

et al.

Seminars in Cancer Biology, Journal Year: 2022, Volume and Issue: 86, P. 827 - 845

Published: Feb. 7, 2022

Language: Английский

Citations

86
Histone Modifications in Alzheimer’s Disease DOI Open Access
Dalileia Aparecida Santana, Marı́lia de Arruda Cardoso Smith, Elizabeth Chen

et al.

Genes, Journal Year: 2023, Volume and Issue: 14(2), P. 347 - 347

Published: Jan. 29, 2023

Since Late-onset Alzheimer's disease (LOAD) derives from a combination of genetic variants and environmental factors, epigenetic modifications have been predicted to play role in the etiopathology LOAD. Along with DNA methylation, histone proposed as main that contribute pathologic mechanisms LOAD; however, little is known about how these disease's onset or progression. In this review, we highlighted their functional role, including acetylation, phosphorylation, well changes such occur aging process mainly (AD). Furthermore, pointed out drugs tested for AD treatment, those based on deacetylase (HDAC) inhibitors. Finally, remarked perspectives around use epigenetics treating AD.

Language: Английский

Citations

62
Aging Hallmarks and Progression and Age-Related Diseases: A Landscape View of Research Advancement DOI Creative Commons

Rumiana Tenchov,

Janet M. Sasso, Xinmei Wang

et al.

ACS Chemical Neuroscience, Journal Year: 2023, Volume and Issue: 15(1), P. 1 - 30

Published: Dec. 14, 2023

Aging is a dynamic, time-dependent process that characterized by gradual accumulation of cell damage. Continual functional decline in the intrinsic ability living organisms to accurately regulate homeostasis leads increased susceptibility and vulnerability diseases. Many efforts have been put forth understand prevent effects aging. Thus, major cellular molecular hallmarks aging identified, their relationships age-related diseases malfunctions explored. Here, we use data from CAS Content Collection analyze publication landscape recent aging-related research. We review advances knowledge delineate trends research advancements on factors attributes across time geography. also current concepts related molecular, cellular, organismic level, age-associated diseases, with attention brain health, as well biochemical processes associated Major outlined, correlations features are hope this will be helpful for apprehending field mechanisms progression, an effort further solve remaining challenges fulfill its potential.

Language: Английский

Citations

60
Genomic Instability and Epigenetic Changes during Aging DOI Open Access

Lucía López-Gil,

Amparo Pascual‐Ahuir, Markus Proft

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(18), P. 14279 - 14279

Published: Sept. 19, 2023

Aging is considered the deterioration of physiological functions along with an increased mortality rate. This scientific review focuses on central importance genomic instability during aging process, encompassing a range cellular and molecular changes that occur advancing age. In particular, this revision addresses genetic epigenetic alterations contribute to instability, such as telomere shortening, DNA damage accumulation, decreased repair capacity. Furthermore, explores aging, including modifications histones, methylation patterns, role non-coding RNAs. Finally, discusses organization chromatin its contribution heterochromatin loss, remodeling, in nucleosome histone abundance. conclusion, highlights fundamental plays process underscores need for continued research into these complex biological mechanisms.

Language: Английский

Citations

47
Depletion of SAM leading to loss of heterochromatin drives muscle stem cell ageing DOI
Jengmin Kang,

Daniel I. Benjamin,

Soochi Kim

et al.

Nature Metabolism, Journal Year: 2024, Volume and Issue: 6(1), P. 153 - 168

Published: Jan. 19, 2024

Language: Английский

Citations

23
Epigenetic reprogramming as a key to reverse ageing and increase longevity DOI Creative Commons
Beatriz Pereira, Francisca P. Correia, Inês A. Alves

et al.

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 95, P. 102204 - 102204

Published: Jan. 23, 2024

The pursuit for the fountain of youth has long been a fascination amongst scientists and humanity. Ageing is broadly characterized by cellular decline with increased susceptibility to age-related diseases, being intimately associated epigenetic modifications. Recently, reprogramming-induced rejuvenation strategies have begun greatly alter longevity research not only tackle defects but also possibly reverse ageing process. Hence, in this review, we highlight major changes during state-of-art current emerging reprogramming leveraging on transcription factors. Notably, partial enables resetting clock without erasing identity. Promising chemical-based harnessing small molecules, including DNA methyltransferase histone deacetylase inhibitors are discussed. Moreover, parallel interventions, foundations clocks accurate assessment evaluation approaches briefly presented. Going further, such scientific breakthroughs, witnessing rise biotech industry aiming extend health span ideally achieve human one day. In context, overview main scenarios proposed future socio-economic ethical challenges an field. Ultimately, review aims inspire interventions that promote healthy all.

Language: Английский

Citations

22
Centromere inactivation during aging can be rescued in human cells DOI Creative Commons
Sweta Sikder, Songjoon Baek,

Truman McNeil

et al.

Molecular Cell, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Aging involves a range of genetic, epigenetic, and physiological alterations. A key characteristic aged cells is the loss global heterochromatin, accompanied by reduction in canonical histone levels. In this study, we track fate centromeres human fibroblasts tissues various cellular senescent models. Our findings reveal that centromeric H3 variant CENP-A downregulated p53-dependent manner. We observe repression noncoding transcription through an epigenetic mechanism via recruitment lysine-specific demethylase 1 (LSD1/KDM1A) to centromeres. This suppression results defective de novo loading at aging By dual inhibition p53 LSD1/KDM1A cells, mitigate proteins transcripts, leading mitotic rejuvenation these cells. These offer insights into unique for inactivation during provide potential strategies reactivate

Language: Английский

Citations

2
New Insights into the Role of Histone Changes in Aging DOI Open Access
Sun-Ju Yi, Kyunghwan Kim

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 21(21), P. 8241 - 8241

Published: Nov. 3, 2020

Aging is the progressive decline or loss of function at cellular, tissue, and organismal levels that ultimately leads to death. A number external internal factors, including diet, exercise, metabolic dysfunction, genome instability, epigenetic imbalance, affect lifespan an organism. These aging factors regulate transcriptome changes related process through chromatin remodeling. Many regulators, such as histone modification, variants, ATP-dependent remodeling play roles in reorganization. The key understanding role gene regulatory networks lies characterizing regulators responsible for reorganizing potentiating particular structures. This review covers studies on aging, discusses impact modifications expression, provides future directions this area.

Language: Английский

Citations

100