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Special Issue "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).

Special Issue Editor

Prof. Dr. Alexey Moskalev
E-Mail
Guest Editor
Moscow Institute of Physics and Technology, Moscow, Russia
Interests: genetics of aging; geroprotectors; biomarkers of aging; genetics of longevity
Special Issues and Collections 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 papers will be 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.

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Published Papers (5 papers)

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Research

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Article
Machine Learning Analysis of Longevity-Associated Gene Expression Landscapes in Mammals
Int. J. Mol. Sci. 2021, 22(3), 1073; https://doi.org/10.3390/ijms22031073 - 22 Jan 2021
Cited by 1 | Viewed by 1363
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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Article
Maternal Responses and Adaptive Changes to Environmental Stress via Chronic Nanomaterial Exposure: Differences in Inter and Transgenerational Interclonal Broods of Daphnia magna
Int. J. Mol. Sci. 2021, 22(1), 15; https://doi.org/10.3390/ijms22010015 - 22 Dec 2020
Viewed by 553
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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Article
Histological Evaluation and Gene Expression Profiling of Autophagy-Related Genes for Cartilage of Young and Senescent Rats
Int. J. Mol. Sci. 2020, 21(22), 8607; https://doi.org/10.3390/ijms21228607 - 15 Nov 2020
Viewed by 518
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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Review
The Role of microRNAs in Organismal and Skin Aging
Int. J. Mol. Sci. 2020, 21(15), 5281; https://doi.org/10.3390/ijms21155281 - 25 Jul 2020
Cited by 4 | Viewed by 1852
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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Review
Genome-Protecting Compounds as Potential Geroprotectors
Int. J. Mol. Sci. 2020, 21(12), 4484; https://doi.org/10.3390/ijms21124484 - 24 Jun 2020
Cited by 2 | Viewed by 2118
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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