Genetic and Epigenetic Mechanisms of Longevity and Aging

A special issue of Biology (ISSN 2079-7737). This special issue belongs to the section "Genetics and Genomics".

Deadline for manuscript submissions: closed (30 November 2022) | Viewed by 13460

Special Issue Editors


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Guest Editor
European Research Institute for The Biology of Ageing (ERIBA), University of Groningen (RUG), 9713 AV Groningen, The Netherlands
Interests: aging; cellular senescence; cancer; extracellular vesicles
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Special Issue Information

Dear Colleagues,

Aging is the inevitable outcome of life and healthy aging can be preserved through interventions.

We are assisting in the increased life expectancy of the population, and in parallel to a rise in research studies on biological and molecular factors implicated in age-related pathologies.

Accumulating evidence links aging to genetic and epigenetic alterations, and studies already suggested that the maintenance of cellular homeostasis, inflammation, oxidative stress response, DNA repair, nutritional intervention, as well as cellular senescence, are crucial players.

This Special Issue is aimed to provide an overview and update in the analysis of the genetic and epigenetic mechanisms of human aging and longevity, to establish links between common gene pathways and hallmark genetic and epigenetic signatures that can be used to identify “druggable” targets to counter age-related disease and promote longevity.

We invite submissions for reviews, research articles, and short manuscripts related to genetic and epigenetic mechanisms in organismal aging and longevity, including characterization of longevity-related genes, analysis of gene expression profiles, novel insight into the regulation of gene expression and gene pathways with the potential of novel therapeutic and rejuvenation approaches to prevention, treatment, diagnosis and prognosis in age-related diseases or to promote longevity.

Dr. Michela Borghesan
Dr. Giulia Accardi
Guest Editors

Manuscript Submission Information

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Keywords

  • genetics of aging
  • cellular aging
  • gene regulation
  • genetic mechanisms of longevity
  • gene expression
  • genetic modulation
  • healthy aging
  • age-related pathologies
  • genetics of longevity
  • epigenetic of longevity
  • epigenetic of aging

Published Papers (5 papers)

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Research

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37 pages, 5634 KiB  
Article
Evaluation of Epigenetic Age Acceleration Scores and Their Associations with CVD-Related Phenotypes in a Population Cohort
by Olga Chervova, Elizabeth Chernysheva , Kseniia Panteleeva , Tyas Arum Widayati , Natalie Hrbkova, Jadesada Schneider , Vladimir Maximov , Andrew Ryabikov , Taavi Tillmann , Hynek Pikhart, Martin Bobak , Vitaly Voloshin , Sofia Malyutina  and Stephan Beck 
Biology 2023, 12(1), 68; https://doi.org/10.3390/biology12010068 - 30 Dec 2022
Cited by 4 | Viewed by 1980
Abstract
We evaluated associations between nine epigenetic age acceleration (EAA) scores and 18 cardiometabolic phenotypes using an Eastern European ageing population cohort richly annotated for a diverse set of phenotypes (subsample, n = 306; aged 45–69 years). This was implemented by splitting the data [...] Read more.
We evaluated associations between nine epigenetic age acceleration (EAA) scores and 18 cardiometabolic phenotypes using an Eastern European ageing population cohort richly annotated for a diverse set of phenotypes (subsample, n = 306; aged 45–69 years). This was implemented by splitting the data into groups with positive and negative EAAs. We observed strong association between all EAA scores and sex, suggesting that any analysis of EAAs should be adjusted by sex. We found that some sex-adjusted EAA scores were significantly associated with several phenotypes such as blood levels of gamma-glutamyl transferase and low-density lipoprotein, smoking status, annual alcohol consumption, multiple carotid plaques, and incident coronary heart disease status (not necessarily the same phenotypes for different EAAs). We demonstrated that even after adjusting EAAs for sex, EAA–phenotype associations remain sex-specific, which should be taken into account in any downstream analysis involving EAAs. The obtained results suggest that in some EAA–phenotype associations, negative EAA scores (i.e., epigenetic age below chronological age) indicated more harmful phenotype values, which is counterintuitive. Among all considered epigenetic clocks, GrimAge was significantly associated with more phenotypes than any other EA scores in this Russian sample. Full article
(This article belongs to the Special Issue Genetic and Epigenetic Mechanisms of Longevity and Aging)
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15 pages, 2965 KiB  
Article
Methionine Metabolism Is Down-Regulated in Heart of Long-Lived Mammals
by Natalia Mota-Martorell, Mariona Jové, Rebeca Berdún, Èlia Òbis, Gustavo Barja and Reinald Pamplona
Biology 2022, 11(12), 1821; https://doi.org/10.3390/biology11121821 - 14 Dec 2022
Cited by 3 | Viewed by 2339
Abstract
Methionine constitutes a central hub of intracellular metabolic adaptations leading to an extended longevity (maximum lifespan). The present study follows a comparative approach analyzing methionine and related metabolite and amino acid profiles using an LC-MS/MS platform in the hearts of seven mammalian species [...] Read more.
Methionine constitutes a central hub of intracellular metabolic adaptations leading to an extended longevity (maximum lifespan). The present study follows a comparative approach analyzing methionine and related metabolite and amino acid profiles using an LC-MS/MS platform in the hearts of seven mammalian species with a longevity ranging from 3.8 to 57 years. Our findings demonstrate the existence of species-specific heart phenotypes associated with high longevity characterized by: (i) low concentration of methionine and its related sulphur-containing metabolites; (ii) low amino acid pool; and (iii) low choline concentration. Our results support the existence of heart metabotypes characterized by a down-regulation in long-lived species, supporting the idea that in longevity, less is more. Full article
(This article belongs to the Special Issue Genetic and Epigenetic Mechanisms of Longevity and Aging)
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11 pages, 1580 KiB  
Article
MEKK-3 Acts Cooperatively with NSY-1 in SKN-1-Dependent Manner against Oxidative Stress and Aging in Caenorhabditis elegans
by Min Hwang, Chandani Shrestha, Shinwon Kang and Jiyoon Kim
Biology 2022, 11(10), 1526; https://doi.org/10.3390/biology11101526 - 18 Oct 2022
Cited by 1 | Viewed by 2116
Abstract
Oxidative stress resulting from reactive oxygen species and other toxic metabolites is involved in human diseases, and it plays an important role in aging. In Caenorhabditis elegans, SKN-1 is required for protection against oxidative stress and aging. As p38 mitogen-activated protein kinase [...] Read more.
Oxidative stress resulting from reactive oxygen species and other toxic metabolites is involved in human diseases, and it plays an important role in aging. In Caenorhabditis elegans, SKN-1 is required for protection against oxidative stress and aging. As p38 mitogen-activated protein kinase signaling is activated in response to oxidative stress, SKN-1 accumulates in intestinal nuclei and induces phase II detoxification genes. However, NSY-1, a well-known mitogen-activated protein kinase kinase kinase (MAPKKK) of C. elegans, acts as a partial regulator of the SKN-1-induced oxidative stress signaling pathway, suggesting that the regulator for optimal activation of SKN-1 remains unknown. Here, we report a MAPKKK, MEKK-3, as a new regulator required for full activation of SKN-1-mediated resistance against oxidative stress and aging. In RNA-interference-based screening, we found that the simultaneous knockdown of mekk-3 and nsy-1 significantly decreased the oxidative stress resistance and survival of SKN-1 transgenic worms. MEKK-3 was induced in response to oxidative stress. Mechanistic analysis revealed that double knockdown of mekk-3 and nsy-1 completely suppressed the nuclear localization of SKN-1. These results were reproduced in mutant worms in which SKN-1 is constitutively localized to intestinal nuclei. In addition, mekk-3 and nsy-1 were required for optimal induction of SKN-1 target genes such as gcs-1 and trx-1. These data indicate that MEKK-3 plays an essential role in the SKN-1-dependent signaling pathway involved in oxidative stress resistance and longevity by cooperating with NSY-1. Full article
(This article belongs to the Special Issue Genetic and Epigenetic Mechanisms of Longevity and Aging)
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15 pages, 1548 KiB  
Article
Transcriptomics and Proteomics Analyses Reveal JAK Signaling and Inflammatory Phenotypes during Cellular Senescence in Blind Mole Rats: The Reflections of Superior Biology
by Nurcan Inci, Erdogan Oguzhan Akyildiz, Abdullah Alper Bulbul, Eda Tahir Turanli, Emel Akgun, Ahmet Tarik Baykal, Faruk Colak and Perinur Bozaykut
Biology 2022, 11(9), 1253; https://doi.org/10.3390/biology11091253 - 23 Aug 2022
Cited by 3 | Viewed by 2419
Abstract
The blind mole rat (BMR), a long-living subterranean rodent, is an exceptional model for both aging and cancer research since they do not display age-related phenotypes or tumor formation. The Janus kinase–signal transducer and activator of transcription (JAK–STAT) signaling is a cytokine-stimulated pathway [...] Read more.
The blind mole rat (BMR), a long-living subterranean rodent, is an exceptional model for both aging and cancer research since they do not display age-related phenotypes or tumor formation. The Janus kinase–signal transducer and activator of transcription (JAK–STAT) signaling is a cytokine-stimulated pathway that has a crucial role in immune regulation, proliferation, and cytokine production. Therefore, the pathway has recently attracted interest in cellular senescence studies. Here, by using publicly available data, we report that JAK–STAT signaling was suppressed in the BMR in comparison to the mouse. Interestingly, our experimental results showed upregulated Jak1/2 expressions in BMR fibroblasts during the replicative senescence process. The transcriptomic analysis using publicly available data also demonstrated that various cytokines related to JAK–STAT signaling were upregulated in the late passage cells, while some other cytokines such as MMPs and SERPINs were downregulated, representing a possible balance of senescence-associated secretory phenotypes (SASPs) in the BMR. Finally, our proteomics data also confirmed cytokine-mediated signaling activation in senescent BMR fibroblasts. Together, our findings suggest the critical role of JAK–STAT and cytokine-mediated signaling pathways during cellular senescence, pointing to the possible contribution of divergent inflammatory factors to the superior resistance of aging and cancer in BMRs. Full article
(This article belongs to the Special Issue Genetic and Epigenetic Mechanisms of Longevity and Aging)
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Review

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23 pages, 1674 KiB  
Review
A Unified Model of Age-Related Cardiovascular Disease
by Michael Fossel, Joe Bean, Nina Khera and Mikhail G. Kolonin
Biology 2022, 11(12), 1768; https://doi.org/10.3390/biology11121768 - 6 Dec 2022
Cited by 10 | Viewed by 3199
Abstract
Despite progress in biomedical technologies, cardiovascular disease remains the main cause of mortality. This is at least in part because current clinical interventions do not adequately take into account aging as a driver and are hence aimed at suboptimal targets. To achieve progress, [...] Read more.
Despite progress in biomedical technologies, cardiovascular disease remains the main cause of mortality. This is at least in part because current clinical interventions do not adequately take into account aging as a driver and are hence aimed at suboptimal targets. To achieve progress, consideration needs to be given to the role of cell aging in disease pathogenesis. We propose a model unifying the fundamental processes underlying most age-associated cardiovascular pathologies. According to this model, cell aging, leading to cell senescence, is responsible for tissue changes leading to age-related cardiovascular disease. This process, occurring due to telomerase inactivation and telomere attrition, affects all components of the cardiovascular system, including cardiomyocytes, vascular endothelial cells, smooth muscle cells, cardiac fibroblasts, and immune cells. The unified model offers insights into the relationship between upstream risk factors and downstream clinical outcomes and explains why interventions aimed at either of these components have limited success. Potential therapeutic approaches are considered based on this model. Because telomerase activity can prevent and reverse cell senescence, telomerase gene therapy is discussed as a promising intervention. Telomerase gene therapy and similar systems interventions based on the unified model are expected to be transformational in cardiovascular medicine. Full article
(This article belongs to the Special Issue Genetic and Epigenetic Mechanisms of Longevity and Aging)
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