Epigenetic Mechanisms of Aging and Aging-Associated Diseases

Abstract

Aging is an inevitable outcome of life, characterized by a progressive decline in tissue and organ function. At a molecular level, it is marked by the gradual alterations of biomolecules. Indeed, important changes are observed on the DNA, as well as at a protein level, that are influenced by both genetic and environmental parameters. These molecular changes directly contribute to the development or progression of several human pathologies, including cancer, diabetes, osteoporosis, neurodegenerative disorders and others aging-related diseases. Additionally, they increase the risk of mortality. Therefore, deciphering the hallmarks of aging represents a possibility for identifying potential druggable targets to attenuate the aging process, and then the age-related comorbidities. Given the link between aging, genetic, and epigenetic alterations, and given the reversible nature of epigenetic mechanisms, the precisely understanding of these factors may provide a potential therapeutic approach for age-related decline and disease. In this review, we center on epigenetic regulatory mechanisms and their aging-associated changes, highlighting their inferences in age-associated diseases.

The Molecular Mechanisms in Senescent Cells Induced by Natural Aging and Ionizing Radiation

“…Over the last decade, a large number of studies have shown that epigenetic changes are one of the major causes of cellular senescence, affecting gene expression, but not disrupting DNA sequences. Epigenetic mechanisms include DNA methylation, histone modification, and changes in non-coding RNA expression [ 114 ].…”

“…Over the last decade, a large number of studies have shown that epigenetic changes are one of the major causes of cellular senescence, affecting gene expression, but not disrupting DNA sequences. Epigenetic mechanisms include DNA methylation, histone modification, and changes in non-coding RNA expression [114]. In a study by Giuliani et al [110], mitomiR-34a, -146, and -181a are overexpressed in replicatively senescent HUVECs, suppressing the activity of the apoptotic protein Bcl-2, which is responsible for the inhibition of apoptosis and autophagy.…”

The Heterogeneity of Post-Menopausal Disease Risk: Could the Basis for Why Only Subsets of Females Are Affected Be Due to a Reversible Epigenetic Modification System Associated with Puberty, Menstrual Cycles, Pregnancy and Lactation, and, Ultimately, Menopause?

“…AA. Epigenetic modifications of the genome via direct methylation or indirectly via modification of histones, as well as modification of RNA can occur under a variety of circumstances (discussed in [78][79][80][81][82]). Many of these alterations are reversible modifications that allow for modulation and regulation of gene expression and function.…”

Effect of resistance training plus enriched probiotic supplement on sestrin2, oxidative stress, and mitophagy markers in elderly male Wistar rats

“…By 2030 and 2050 the proportion of this age group is projected to be 12% and 16%, respectively 2 . Several molecular mechanisms that regulate aging have been discovered, such as telomere dysfunction 3 , loss of proteostasis 4 , mitochondrial dysfunction 5 , stem cell exhaustion 6 , and epigenetic alterations 7 . The aging process is driven by several complex and important pathways, many of which are associated with chronic oxidative stress (OS) caused by elevated levels of reactive oxygen species (ROS) 8 .…”