NAD + in Aging: Molecular Mechanisms and Translational Implications

Trends Mol Med. 2017 Oct;23(10):899-916. doi: 10.1016/j.molmed.2017.08.001. Epub 2017 Sep 9.

Abstract

The coenzyme NAD+ is critical in cellular bioenergetics and adaptive stress responses. Its depletion has emerged as a fundamental feature of aging that may predispose to a wide range of chronic diseases. Maintenance of NAD+ levels is important for cells with high energy demands and for proficient neuronal function. NAD+ depletion is detected in major neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases, cardiovascular disease and muscle atrophy. Emerging evidence suggests that NAD+ decrements occur in various tissues during aging, and that physiological and pharmacological interventions bolstering cellular NAD+ levels might retard aspects of aging and forestall some age-related diseases. Here, we discuss aspects of NAD+ biosynthesis, together with putative mechanisms of NAD+ action against aging, including recent preclinical and clinical trials.

Keywords: DNA repair; NAD(+); aging; autophagy; clinical application; metabolism; mitophagy; neurodegenerative disorder; stem cell.

Publication types

  • Review
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / metabolism*
  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / pathology
  • Alzheimer Disease / therapy
  • Animals
  • Cardiovascular Diseases / metabolism*
  • Cardiovascular Diseases / pathology
  • Cardiovascular Diseases / therapy
  • Energy Metabolism*
  • Humans
  • Muscular Atrophy / metabolism*
  • Muscular Atrophy / pathology
  • Muscular Atrophy / therapy
  • NAD
  • Parkinson Disease / metabolism*
  • Parkinson Disease / pathology
  • Parkinson Disease / therapy

Substances

  • NAD