Figure 3 from Genomic instability in the naturally and prematurely aged myocardium | Semantic Scholar (2024)

Test the hypothesis that endogenous DNA repair in cardiomyocytes is critical for maintaining normal cardiac function, so that perturbed repair of spontaneous DNA damage drives early onset of heart failure and implicate DNA damage as a potential novel therapeutic target.

Data support the conclusion that DNA damage produced endogenously can drive cardiac disease and does so mechanistically via chronic activation of p53 and increased oxidative stress, driving cardiac myocyte apoptosis, dilated cardiomyopathy, and sudden death.

It is shown that DNA damage accumulation led to the increase in CHK2 protein level, which enhanced the interaction between LKB1 and AMPKα, thereby promoting LKB1-mediated AMPKα phosphorylation and activating pro-atrophic signaling cascade.

This review provides insights into novel histone expression profiles, nucleosome occupancy, disruptions in higher-order chromatin architecture, and the emergence of noncanonical histone variants in the aging cellular landscape.

This is the first identification of the genome-wide DSBs, at the nucleotide resolution in the cardiovascular system, and the prevalence of DSBs was higher in the genomic regions associated with transcription.

Investigating the impact of age‐related changes on histone levels and histone acetylation in the retinal pigment epithelium (RPE) and retina of mice strongly demonstrates histone loss as a unique feature of RPE aging and provides critical insights into the potential mechanisms linking histone dynamics, cellular senescence, and aging.

This Review posit that eight molecular hallmarks are common denominators in cardiovascular ageing, namely disabled macroautophagy, loss of proteostasis, genomic instability, epigenetic alterations, mitochondrial dysfunction, cell senescence, dysregulated neurohormonal signalling and inflammation, and proposes a hierarchical order that distinguishes primary from antagonistic and integrative (downstream) hallmarks of cardiovascular ageing.

The chromatin accessibility in control cochlear tissue was higher than that in cochlear tissue affected by ARHL, and potential SEs involved in ARHL were identified, which might provide a basis for future therapeutics targeting SASEs related to ARHL.

The hallmarks of aging are discussed and the potential role of stem cells and cryopreservation of embryos, oocytes, or ovarian tissue in the delay of ovarian aging is elaborated.

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High‐throughput proteomics of the hearts of progeric and normally aged mice revealed altered protein oxidation and glycation, as well as dysregulated pathways regulating energy metabolism, proteostasis, gene expression, and cardiac muscle contraction, which could help in the design of strategies to prevent or slow age‐related cardiometabolic disease.

Antisense oligonucleotides reverse premature aging and extend life span in mutant mice that mimic aberrant splicing in progeria patients and develop an antisense morpholino–based therapy that prevents the pathogenic Lmna splicing.

The main structural and functional alterations to the cardiovascular system during physiological and premature aging are summarized and the mechanisms underlying exaggerated CVD and aging induced by prelamin A and progerin are discussed.

Some of the key genes involved in regulating lifespan and health span, including sirtuins, AMP-activated protein kinase, mammalian target of rapamycin, and insulin-like growth factor 1 and their roles regulating cardiovascular health are provided.

The use of a transgenic mouse model, harboring lacZ reporter genes as part of a plasmid construct integrated at one or more chromosomal locations, is described to study genomic instability during aging of different mouse organs and tissues as well as in mouse embryonic fibroblasts during primary culture.

The accumulating evidence that resident cardiomyocytes can be stimulated to proliferate holds promise for the development of new and more effective treatments for the most devastating types of cardiovascular disease.

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