About this Research Topic
Advances in Metabolic Mechanisms of Aging and Its Related Diseases
Aging is an intricate and multifactorial process characterized by increased risk of adverse health outcomes. It is accompanied by the loss of cellular homeostasis that leads to degeneration of multiple organ systems. A better understanding of aging, with the aim of halting this process and preventing or even treating the related pathologies is of healthcare priority.
Alterations of the redox homeostasis, characterized by the imbalance of redox couples (NADH/NAD, NADPH/NADP, GSH/GSSG, cysteine/cystine) and altered production of redox signaling molecules (e.g. nitric oxide), are crucially involved in aging (redox theory of aging) as they participate in several physiological processes such as cell differentiation, detoxification, antioxidant defense, control of metabolic homeostasis and immune system.
Mitochondria are at the center of several pathways in cell homeostasis due to their key function in bioenergetics, metabolism, generation of reactive oxygen species, apoptosis, and signal transduction. For several years, a central role in aging has principally been ascribed to mitochondria, as a decline in mitochondrial activity and quality occurs during aging in a time-dependent manner and correlates with accumulation of oxidatively damaged molecules (lipids, DNA, proteins) and the development of a wide range of age-related pathologies (e.g. neurodegenerative diseases, cancer, diabetes, NAFLD).
Findings from animal and cellular models in conjunction with high-throughput experimental tools have advanced our understanding of pathways underlying the aging process that are not exclusively linked to mitochondrial dysfunction and oxidative stress, highlighting possible new interventional targets.
A plethora of interconnected signaling pathways that decline during aging has now emerged. All these pathways counteract environmental insults (exposome) by assuring metabolic flexibility, organelles quality control (e.g. autophagy, unfolded protein response), DNA and protein repair allowing healthy aging to succeeds. Associated with aging is diminished insulin sensitivity and impaired glucose and lipid metabolism that leads to a dysregulation of metabolic homeostasis usually manifested as age-related obesity and diabetes (i.e. type 2 diabetes). Insulin/IGF-1 signaling and the mechanistic Target Of Rapamycin (mTOR) pathways are up-regulated in aging and their inhibition is associated with prolonged lifespan and health span in a number of model organisms.
The aging tissue/cell is also characterized by a profound remodeling of the transcriptome profile also due to significant epigenetic modifications. microRNAs are novel regulators of gene expression known to modulate cell development and homeostasis. Expression of numerous microRNAs is altered with age. Since a single microRNA can simultaneously affect multiple signaling pathways, changes in miRNAs expression occurring during aging lead to severe pathophysiological consequences.
In this Research Topic we intend to describe novel metabolic pathways also involving mitochondria that play a significant role in committing aging or prolong health span. We also encourage the submission of papers that suggest innovative strategies as well as model systems to identify possible genetic modifiers to retard aging and prevent the development of age-related metabolic diseases.
Keywords: Mitochondrion, Environmental stress, Immune Metabolism, Cell Signalling, Epigenetics
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