NAD metabolism: Role in senescence regulation and aging

Author:

Chini Claudia Christiano Silva12ORCID,Cordeiro Heidi Soares12,Tran Ngan Le Kim3,Chini Eduardo Nunes12ORCID

Affiliation:

1. Metabolism and Molecular Nutrition Laboratory, Kogod Center on Aging, Department of Anesthesiology and Perioperative Medicine Mayo Clinic College of Medicine Rochester Minnesota USA

2. Metabolism and Molecular Nutrition Laboratory, Kogod Center on Aging, Department of Anesthesiology and Perioperative Medicine Mayo Clinic College of Medicine Jacksonville Florida USA

3. Center for Clinical and Translational Science and Mayo Clinic Graduate School of Biomedical Sciences Mayo Clinic Jacksonville Florida USA

Abstract

AbstractThe geroscience hypothesis proposes that addressing the biology of aging could directly prevent the onset or mitigate the severity of multiple chronic diseases. Understanding the interplay between key aspects of the biological hallmarks of aging is essential in delivering the promises of the geroscience hypothesis. Notably, the nucleotide nicotinamide adenine dinucleotide (NAD) interfaces with several biological hallmarks of aging, including cellular senescence, and changes in NAD metabolism have been shown to be involved in the aging process. The relationship between NAD metabolism and cellular senescence appears to be complex. On the one hand, the accumulation of DNA damage and mitochondrial dysfunction induced by low NAD+ can promote the development of senescence. On the other hand, the low NAD+ state that occurs during aging may inhibit SASP development as this secretory phenotype and the development of cellular senescence are both highly metabolically demanding. However, to date, the impact of NAD+ metabolism on the progression of the cellular senescence phenotype has not been fully characterized. Therefore, to explore the implications of NAD metabolism and NAD replacement therapies, it is essential to consider their interactions with other hallmarks of aging, including cellular senescence. We propose that a comprehensive understanding of the interplay between NAD boosting strategies and senolytic agents is necessary to advance the field.

Funder

National Center for Advancing Translational Sciences

National Institutes of Health

Publisher

Wiley

Subject

Cell Biology,Aging

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