Metabolic and Redox Regulation at the Center of Aging

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About this Research Topic

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Background

There has been a long-standing interest in defining how aging modulates metabolic and redox-related pathways, and how metabolic and redox activities regulate the aging process. A notable example is the positive impact of dietary restriction on longevity, which has been shown in many animal models. As whole body metabolism is regulated by a variety of neuronal, hormonal, physical, chemical, and microbiomic factors, understanding how these factors function in aging is of paramount importance.

At a cellular level, metabolism is largely associated with mitochondrial function, as it controls energy production, synthesis of metabolites, and reactive species that affect the activities of metabolic enzymes. In the context of aging, mitochondrial quality control, a process modulated by mitophagy, has been extensively examined in various cell and tissue setting. Mitochondria-nuclear interaction also modulate the aging process. Interventions using mitochondrial-targeted pharmacological agents have been investigated in the context of aging. At a molecular level, inhibition of the nutrient sensing mTOR signaling pathway has been tested to enhance longevity in several species, while mechanisms involving metabolism and redox regulation are currently being investigated.

The oxidative stress theory of aging relates redox-related events to longevity. Initially, it was observed that aging cells and tissues accumulate damaged DNA, lipid, proteins, and organelles, which in turn influence bioenergetics. Naturally, these ideas continue to evolve as we gain a better understanding of the biology involved. Central to the control of cellular damages are not only processes with antioxidant production, but also autophagy, a process activated by starvation, which provide means to clean existing cellular damage. It is now also clear that, Nrf2, a transcription factor that regulates genes encoding antioxidants, is linked to both autophagy regulation and metabolism. For example, the Nrf2 function has been found to affect the aging process of tissue including, but not limited to, the heart and the brain. With the recent advancement of the ability to investigate cross-tissue regulation, integrate genomics, transcriptomics, proteomics, and metabolomics into conceptual networks, a better understanding of the mechanisms and regulation of aging, in the context of metabolism and redox biology, will provide significant insights into aging biology and age-associated diseases.

Through this Research Topic, we encourage authors to link basic aging biology to clinical investigation of metabolism and redox biology in aging. We invite original mechanistic research aimed at linking metabolism and redox regulation to aging. We also invite reviews of the literature in which new hypotheses are proposed describing how specific metabolic and redox changes may exacerbate or attenuate aging and age-related diseases.

Keywords: oxidative stress, autophagy, redox regulation, bioenergetics, aging

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