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Genetics and Epigenetics of Aging and Longevity
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Genetics and Epigenetics of Aging and Longevity

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Genetics and Genomics".

Deadline for manuscript submissions: closed (16 November 2020) | Viewed by 36407

Special Issue Editor

Prof. Dr. Alexey Moskalev

E-Mail Website
Guest Editor
Moscow Institute of Physics and Technology, Moscow, Russia
Interests: genetics of aging; geroprotectors; biomarkers of aging; genetics of longevity
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

It is my pleasure to announce the launch of a new Special Issue on the topic of “Genetics and Epigenetics of Aging and Longevity”.

Lifespan is a complex quantitative characteristic that makes a significant contribution to Darwinian adaptiveness. The disclosure of the genetic and epigenetic structure of longevity is a fundamental problem of the evolution of ontogeny, evolutionary genetics, and molecular gerontology. Under optimal conditions, the lifespan is determined by the aging rate. The aging process is made up of interrelated processes that take place at the organismal, tissue, cellular, molecular, and genetic levels. These include deregulation processes of homeostasis maintenance, metabolic reactions, and sending intra­ and intercellular signals, accumulation of senescent cells, damaged organelles and macromolecules, epigenetic changes, and genetic instability. The objective of this topic is to summarize the available information about underlying genetic and epigenetic determinants of longevity and aging. Genes and signaling pathways that regulate stress response, metabolism, growth of cells and organisms, maintaining of genome and proteome integrity, mitochondria quality, inflammatory response, apoptosis and selection of viable cells, as well as circadian rhythms are involved in longevity. The redistribution of energy resources from one pathway to the other can induce or inhibit the “longevity program”, providing increased vitality and aging slowdown. Based on the analysis of geroprotective potential of examined genes’ regulation, the main targets have been identified to slowdown aging and achieve healthy longevity. These trends include heterochromatin recovery, retrotransposition suppression, and aneuploidy elimination; restoring the acidity of lysosomes; telomere elongation; suppression of chronic inflammation; elimination of protein crosslinks; elimination of senescent cells; recovery of NAD+ levels; inhibition of mTOR, S6K, TGF­β, and AT1; and controlled activation of the “longevity program” genes FOXO, AMPK, PGC1α, and NRF2. This topic could help toward a better understanding of the mechanisms of aging and longevity and identification of new biomarkers of aging and longevity interventions and could increase their translational potential.

Prof. Alexey Moskalev
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Published Papers (6 papers)

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Research

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34 pages, 4801 KiB  
Article
The Effects of Nutrient Signaling Regulators in Combination with Phytocannabinoids on the Senescence-Associated Phenotype in Human Dermal Fibroblasts
by Marta Gerasymchuk, Gregory Ian Robinson, Olga Kovalchuk and Igor Kovalchuk
Int. J. Mol. Sci. 2022, 23(15), 8804; https://doi.org/10.3390/ijms23158804 - 8 Aug 2022
Cited by 8 | Viewed by 2997
Abstract
Identifying effective anti-aging compounds is a cornerstone of modern longevity, aging, and skin-health research. There is considerable evidence of the effectiveness of nutrient signaling regulators such as metformin, resveratrol, and rapamycin in longevity and anti-aging studies; however, their potential protective role in skin [...] Read more.
Identifying effective anti-aging compounds is a cornerstone of modern longevity, aging, and skin-health research. There is considerable evidence of the effectiveness of nutrient signaling regulators such as metformin, resveratrol, and rapamycin in longevity and anti-aging studies; however, their potential protective role in skin aging is controversial. In light of the increasing appearance of phytocannabinoids in beauty products without rigorous research on their rejuvenation efficacy, we decided to investigate the potential role of phytocannabinoids in combination with nutrient signaling regulators in skin rejuvenation. Utilizing CCD-1064Sk skin fibroblasts, the effect of metformin, triacetylresveratrol, and rapamycin combined with phytocannabinoids on cellular viability, functional activity, metabolic function, and nuclear architecture was tested. We found triacetylresveratrol combined with cannabidiol increased the viability of skin fibroblasts (p < 0.0001), restored wound-healing functional activity (p < 0.001), reduced metabolic dysfunction, and ameliorated nuclear eccentricity and circularity in senescent fibroblasts (p < 0.01). Conversely, metformin with or without phytocannabinoids did not show any beneficial effects on functional activity, while rapamycin inhibited cell viability (p < 0.01) and the speed of wound healing (p < 0.001). Therefore, triacetylresveratrol and cannabidiol can be a valuable source of biologically active substances used in aging and more studies using animals to confirm the efficacy of cannabidiol combined with triacetylresveratrol should be performed. Full article
(This article belongs to the Special Issue Genetics and Epigenetics of Aging and Longevity)
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21 pages, 2423 KiB  
Article
Machine Learning Analysis of Longevity-Associated Gene Expression Landscapes in Mammals
by Anton Y. Kulaga, Eugen Ursu, Dmitri Toren, Vladyslava Tyshchenko, Rodrigo Guinea, Malvina Pushkova, Vadim E. Fraifeld and Robi Tacutu
Int. J. Mol. Sci. 2021, 22(3), 1073; https://doi.org/10.3390/ijms22031073 - 22 Jan 2021
Cited by 6 | Viewed by 9609
Abstract
One of the important questions in aging research is how differences in transcriptomics are associated with the longevity of various species. Unfortunately, at the level of individual genes, the links between expression in different organs and maximum lifespan (MLS) are yet to be [...] Read more.
One of the important questions in aging research is how differences in transcriptomics are associated with the longevity of various species. Unfortunately, at the level of individual genes, the links between expression in different organs and maximum lifespan (MLS) are yet to be fully understood. Analyses are complicated further by the fact that MLS is highly associated with other confounding factors (metabolic rate, gestation period, body mass, etc.) and that linear models may be limiting. Using gene expression from 41 mammalian species, across five organs, we constructed gene-centric regression models associating gene expression with MLS and other species traits. Additionally, we used SHapley Additive exPlanations and Bayesian networks to investigate the non-linear nature of the interrelations between the genes predicted to be determinants of species MLS. Our results revealed that expression patterns correlate with MLS, some across organs, and others in an organ-specific manner. The combination of methods employed revealed gene signatures formed by only a few genes that are highly predictive towards MLS, which could be used to identify novel longevity regulator candidates in mammals. Full article
(This article belongs to the Special Issue Genetics and Epigenetics of Aging and Longevity)
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21 pages, 3501 KiB  
Article
Maternal Responses and Adaptive Changes to Environmental Stress via Chronic Nanomaterial Exposure: Differences in Inter and Transgenerational Interclonal Broods of Daphnia magna
by Laura-Jayne. A. Ellis, Stephen Kissane and Iseult Lynch
Int. J. Mol. Sci. 2021, 22(1), 15; https://doi.org/10.3390/ijms22010015 - 22 Dec 2020
Cited by 7 | Viewed by 2573
Abstract
There is increasing recognition that environmental nano-biological interactions in model species, and the resulting effects on progeny, are of paramount importance for nanomaterial (NM) risk assessment. In this work, Daphnia magna F0 mothers were exposed to a range of silver and titanium dioxide [...] Read more.
There is increasing recognition that environmental nano-biological interactions in model species, and the resulting effects on progeny, are of paramount importance for nanomaterial (NM) risk assessment. In this work, Daphnia magna F0 mothers were exposed to a range of silver and titanium dioxide NMs. The key biological life history traits (survival, growth and reproduction) of the F1 intergenerations, at the first (F1B1), third (F1B3) and fifth (F1B5) broods, were investigated. Furthermore, the F1 germlines of each of the three broods were investigated over 3 more generations (up to 25 days each) in continuous or removed-from NM exposure, to identify how the length of maternal exposure affects the resulting clonal broods. Our results show how daphnids respond to NM-induced stress, and how the maternal effects show trade-offs between growth, reproduction and survivorship. The F1B1 (and following germline) had the shortest F0 maternal exposure times to the NMs, and thus were the most sensitive showing reduced size and reproductive output. The F1B3 generation had a sub-chronic maternal exposure, whereas the F1B5 generation suffered chronic maternal exposure where (in most cases) the most compensatory adaptive effects were displayed in response to the prolonged NM exposure, including enhanced neonate output and reduced gene expression. Transgenerational responses of multiple germlines showed a direct link with maternal exposure time to ‘sub-lethal’ effect concentrations of NMs (identified from standard OECDs acute toxicity tests which chronically presented as lethal) including increased survival and production of males in the F1B3 and G1B5 germlines. This information may help to fine-tune environmental risk assessments of NMs and prediction of their impacts on environmental ecology. Full article
(This article belongs to the Special Issue Genetics and Epigenetics of Aging and Longevity)
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15 pages, 4510 KiB  
Article
Histological Evaluation and Gene Expression Profiling of Autophagy-Related Genes for Cartilage of Young and Senescent Rats
by Consuelo Arias, Nicolás Saavedra, Karla Leal, Bélgica Vásquez, Dulcineia S. P. Abdalla and Luis A. Salazar
Int. J. Mol. Sci. 2020, 21(22), 8607; https://doi.org/10.3390/ijms21228607 - 15 Nov 2020
Cited by 6 | Viewed by 2140
Abstract
Autophagy is a cellular mechanism that protects cells from stress by digesting non-functional cellular components. In the cartilage, chondrocytes depend on autophagy as a principal mechanism to maintain cellular homeostasis. This protective role diminishes prior to the structural damage that normally occurs during [...] Read more.
Autophagy is a cellular mechanism that protects cells from stress by digesting non-functional cellular components. In the cartilage, chondrocytes depend on autophagy as a principal mechanism to maintain cellular homeostasis. This protective role diminishes prior to the structural damage that normally occurs during aging. Considering that aging is the main risk factor for osteoarthritis, evaluating the expression of genes associated with autophagy in senescent cartilage might allow for the identification of potential therapeutic targets for treatment. Thus, we studied two groups of young and senescent rats. A histological analysis of cartilage and gene expression quantification for autophagy-related genes were performed. In aged cartilage, morphological changes were observed, such as an increase in cartilage degeneration as measured by the modified Mankin score, a decrease in the number of chondrocytes and collagen II (Col2a1), and an increase in matrix metalloproteinase 13 (Mmp13). Moreover, 84 genes associated with autophagy were evaluated by a PCR array analysis, and 15 of them were found to be significantly decreased with aging. Furthermore, an in silico analysis based on by two different bioinformatics software tools revealed that several processes including cellular homeostasis, autophagosome assembly, and aging—as well as several biological pathways such as autophagy, insulin-like growth factor 1 (IGF-1) signaling, PI3K (phosphoinositide 3-kinase)/AKT (serine/threonine kinase) signaling, and mammalian target of rapamycin (mTOR) signaling—were enriched. In conclusion, the analysis identified some potential targets for osteoarthritis treatment that would allow for the development of new therapeutic strategies for this chronic disease. Full article
(This article belongs to the Special Issue Genetics and Epigenetics of Aging and Longevity)
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Review

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36 pages, 2812 KiB  
Review
The Role of microRNAs in Organismal and Skin Aging
by Marta Gerasymchuk, Viktoriia Cherkasova, Olga Kovalchuk and Igor Kovalchuk
Int. J. Mol. Sci. 2020, 21(15), 5281; https://doi.org/10.3390/ijms21155281 - 25 Jul 2020
Cited by 57 | Viewed by 9978
Abstract
The aging process starts directly after birth and lasts for the entire lifespan; it manifests itself with a decline in an organism’s ability to adapt and is linked to the development of age-related diseases that eventually lead to premature death. This review aims [...] Read more.
The aging process starts directly after birth and lasts for the entire lifespan; it manifests itself with a decline in an organism’s ability to adapt and is linked to the development of age-related diseases that eventually lead to premature death. This review aims to explore how microRNAs (miRNAs) are involved in skin functioning and aging. Recent evidence has suggested that miRNAs regulate all aspects of cutaneous biogenesis, functionality, and aging. It has been noted that some miRNAs were down-regulated in long-lived individuals, such as let-7, miR-17, and miR-34 (known as longevity-related miRNAs). They are conserved in humans and presumably promote lifespan prolongation; conversely, they are up-regulated in age-related diseases, like cancers. The analysis of the age-associated cutaneous miRNAs revealed the increased expression of miR-130, miR-138, and miR-181a/b in keratinocytes during replicative senescence. These miRNAs affected cell proliferation pathways via targeting the p63 and Sirtuin 1 mRNAs. Notably, miR-181a was also implicated in skin immunosenescence, represented by the Langerhans cells. Dermal fibroblasts also expressed increased the levels of the biomarkers of aging that affect telomere maintenance and all phases of the cellular life cycle, such as let-7, miR-23a-3p, 34a-5p, miR-125a, miR-181a-5p, and miR-221/222-3p. Among them, the miR-34 family, stimulated by ultraviolet B irradiation, deteriorates collagen in the extracellular matrix due to the activation of the matrix metalloproteinases and thereby potentiates wrinkle formation. In addition to the pro-aging effects of miRNAs, the plausible antiaging activity of miR-146a that antagonized the UVA-induced inhibition of proliferation and suppressed aging-related genes (e.g., p21WAF-1, p16, and p53) through targeting Smad4 has also been noticed. Nevertheless, the role of miRNAs in skin aging is still not fully elucidated and needs to be further discovered and explained. Full article
(This article belongs to the Special Issue Genetics and Epigenetics of Aging and Longevity)
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91 pages, 1602 KiB  
Review
Genome-Protecting Compounds as Potential Geroprotectors
by Ekaterina Proshkina, Mikhail Shaposhnikov and Alexey Moskalev
Int. J. Mol. Sci. 2020, 21(12), 4484; https://doi.org/10.3390/ijms21124484 - 24 Jun 2020
Cited by 18 | Viewed by 8129
Abstract
Throughout life, organisms are exposed to various exogenous and endogenous factors that cause DNA damages and somatic mutations provoking genomic instability. At a young age, compensatory mechanisms of genome protection are activated to prevent phenotypic and functional changes. However, the increasing stress and [...] Read more.
Throughout life, organisms are exposed to various exogenous and endogenous factors that cause DNA damages and somatic mutations provoking genomic instability. At a young age, compensatory mechanisms of genome protection are activated to prevent phenotypic and functional changes. However, the increasing stress and age-related deterioration in the functioning of these mechanisms result in damage accumulation, overcoming the functional threshold. This leads to aging and the development of age-related diseases. There are several ways to counteract these changes: (1) prevention of DNA damage through stimulation of antioxidant and detoxification systems, as well as transition metal chelation; (2) regulation of DNA methylation, chromatin structure, non-coding RNA activity and prevention of nuclear architecture alterations; (3) improving DNA damage response and repair; (4) selective removal of damaged non-functional and senescent cells. In the article, we have reviewed data about the effects of various trace elements, vitamins, polyphenols, terpenes, and other phytochemicals, as well as a number of synthetic pharmacological substances in these ways. Most of the compounds demonstrate the geroprotective potential and increase the lifespan in model organisms. However, their genome-protecting effects are non-selective and often are conditioned by hormesis. Consequently, the development of selective drugs targeting genome protection is an advanced direction. Full article
(This article belongs to the Special Issue Genetics and Epigenetics of Aging and Longevity)
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