Chromatin and Aging

Purohit, Jogeswar S.; Chaturvedi, Madan M.

doi:10.1007/978-981-10-2155-8_11

Cited by 7 publications

(11 citation statements)

References 200 publications

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“…Moreover, alterations in nuclear organization and function are pronounced upon physiological and mitochondrial stress and during premature and physiological aging [ 20 , 27 , 41 , 42 ]. Regarding the higher-order chromatin organization and its involvement in aging several groups have reported the role of lamins in aging [ 23 , 43 ], thus insisting on detailed studies on the role of higher-order chromatin dynamics in aging [ 27 , 44 ]. Our previous research has studied the way higher-order chromatin organization changes during CLS in yeast mutants that lack the gene for the linker histone and results are published elsewhere [ 27 ].…”

Section: Resultsmentioning

confidence: 99%

“…Since aging is associated with major changes in chromatin, and vice versa, as well as with histone and heterochromatin loss [ 20 , 44 ], it was of interest for our work to see the dynamics of HHO1 (the gene for the S. cerevisiae linker histone [ 33 ]) expression in the timeline of yeast CLS under UVA/B stress. Moreover, other authors’ work implied that the linker histone H1 is lost in senescent cells correlating with the formation of senescence-associated heterochromatic foci (SAHFs) [ 52 ].…”

Section: Resultsmentioning

confidence: 99%

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Changes in Chromatin Organization Eradicate Cellular Stress Resilience to UVA/B Light and Induce Premature Aging

Vasileva

Staneva

Krasteva

et al. 2021

Cells

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Complex interactions among DNA and nuclear proteins maintain genome organization and stability. The nuclear proteins, particularly the histones, organize, compact, and preserve the stability of DNA, but also allow its dynamic reorganization whenever the nuclear processes require access to it. Five histone classes exist and they are evolutionarily conserved among eukaryotes. The linker histones are the fifth class and over time, their role in chromatin has been neglected. Linker histones interact with DNA and the other histones and thus sustain genome stability and nuclear organization. Saccharomyces cerevisiae is a brilliant model for studying linker histones as the gene for it is a single-copy and is non-essential. We, therefore, created a linker histone-free yeast strain using a knockout of the relevant gene and traced the way cells age chronologically. Here we present our results demonstrating that the altered chromatin dynamics during the chronological lifespan of the yeast cells with a mutation in ARP4 (the actin-related protein 4) and without the gene HHO1 for the linker histone leads to strong alterations in the gene expression profiles of a subset of genes involved in DNA repair and autophagy. The obtained results further prove that the yeast mutants have reduced survival upon UVA/B irradiation possibly due to the accelerated decompaction of chromatin and impaired proliferation. Our hypothesis posits that the higher-order chromatin structure and the interactions among chromatin proteins are crucial for the maintenance of chromatin organization during chronological aging under optimal and UVA-B stress conditions.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Changes in Chromatin Organization Eradicate Cellular Stress Resilience to UVA/B Light and Induce Premature Aging

Vasileva

Staneva

Krasteva

et al. 2021

Cells

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“…One caveat to these studies is that we do not know whether old and young worms’ chromosomes are equally responsive to irradiation. However, since the nuclear envelope integrity deteriorates ( Haithcock et al, 2005 ; D’Angelo et al, 2009 ) and chromatin decompacts in older animals (reviewed in Purohit and Chaturvedi, 2017 ; Sławińska and Krupa, 2021 ), we would anticipate that DNA damage would increase rather than decrease in older nuclei ( Hernández et al, 2015 ). Further studies on the accessibility of chromatin to DNA damage and developing assay to directly monitor breaks in this system are an avenue of future studies.…”

Section: Discussionmentioning

confidence: 99%

Aging Negatively Impacts DNA Repair and Bivalent Formation in the C. elegans Germ Line

Raices

Bowman

Smolikove

et al. 2021

Front. Cell Dev. Biol.

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Defects in crossover (CO) formation during meiosis are a leading cause of birth defects, embryonic lethality, and infertility. In a wide range of species, maternal aging increases aneuploidy and decreases oocyte quality. In C. elegans which produce oocytes throughout the first half of adulthood, aging both decreases oocytes quality and increases meiotic errors. Phenotypes of mutations in genes encoding double-strand break (DSB)-associated proteins get more severe with maternal age suggesting that early meiosis reflects a particularly sensitive node during reproductive aging in the worm. We observed that aging has a direct effect on the integrity of C. elegans meiotic CO formation, as observed by an increase of univalent chromosomes and fusions at diakinesis, with a considerable increase starting at 4 days. We also characterize the possible causes for the age-related changes in CO formation by analyzing both steady-state levels and kinetics of the ssDNA binding proteins RPA-1 and RAD-51. Profound reductions in numbers of both RPA-1 and RAD-51 foci suggests that both DSB formation and early meiotic repair are compromised in aging worms. Using laser microirradiation and γ-irradiation to induce exogenous damage, we show specifically that recruitment of these homologous recombination proteins is altered. Repair defects can be seen in two-and-one-half day-old adults making the loss of germline repair capacity among the earliest aging phenotypes in the worm.

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“…Although the molecular mechanism by which methylation modulates aging is still unknown, the results obtained from different experimental models such as Drosophila and mammals highlight a correlation between DNA methylation and aging and suggest that DNA methylation could be used as a general biomarker for aging [ 111 ].…”

Section: Epigenetic Regulation Of Nmj Dysfunctionmentioning

confidence: 99%

Age-Related Alterations at Neuromuscular Junction: Role of Oxidative Stress and Epigenetic Modifications

Dobrowolny

Barbiera

Sica

et al. 2021

Cells

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With advancing aging, a decline in physical abilities occurs, leading to reduced mobility and loss of independence. Although many factors contribute to the physio-pathological effects of aging, an important event seems to be related to the compromised integrity of the neuromuscular system, which connects the brain and skeletal muscles via motoneurons and the neuromuscular junctions (NMJs). NMJs undergo severe functional, morphological, and molecular alterations during aging and ultimately degenerate. The effect of this decline is an inexorable decrease in skeletal muscle mass and strength, a condition generally known as sarcopenia. Moreover, several studies have highlighted how the age-related alteration of reactive oxygen species (ROS) homeostasis can contribute to changes in the neuromuscular junction morphology and stability, leading to the reduction in fiber number and innervation. Increasing evidence supports the involvement of epigenetic modifications in age-dependent alterations of the NMJ. In particular, DNA methylation, histone modifications, and miRNA-dependent gene expression represent the major epigenetic mechanisms that play a crucial role in NMJ remodeling. It is established that environmental and lifestyle factors, such as physical exercise and nutrition that are susceptible to change during aging, can modulate epigenetic phenomena and attenuate the age-related NMJs changes. This review aims to highlight the recent epigenetic findings related to the NMJ dysregulation during aging and the role of physical activity and nutrition as possible interventions to attenuate or delay the age-related decline in the neuromuscular system.

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Chromatin and Aging

Cited by 7 publications

References 200 publications

Changes in Chromatin Organization Eradicate Cellular Stress Resilience to UVA/B Light and Induce Premature Aging

Changes in Chromatin Organization Eradicate Cellular Stress Resilience to UVA/B Light and Induce Premature Aging

Aging Negatively Impacts DNA Repair and Bivalent Formation in the C. elegans Germ Line

Age-Related Alterations at Neuromuscular Junction: Role of Oxidative Stress and Epigenetic Modifications

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