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Updated: Dec 8, 2025

Telomere Length and Telomerase Activity; A Yin and Yang of Cell Senescence
12:08

Telomere Length and Telomerase Activity; A Yin and Yang of Cell Senescence

Published on: May 22, 2013

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Re-equilibration of imbalanced NAD metabolism ameliorates the impact of telomere dysfunction

Chongkui Sun1, Kun Wang1, Amanda J Stock1

  • 1Biomedical Research Center, National Institute on Aging/National Institutes of Health, Baltimore, MD, USA.

The EMBO Journal
|September 16, 2020
PubMed

Insights

Short telomeres in telomere biology disorders are linked to low nicotinamide adenine dinucleotide (NAD) levels. Restoring NAD homeostasis with precursors or CD38 inhibition improved cell health and alleviated damage in related diseases.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Genetics

Background:

  • Short telomeres characterize telomere biology disorders like dyskeratosis congenita (DC).
  • Currently, no effective treatments exist for DC.
  • Telomere dysfunction impacts cellular health and organismal aging.

Purpose of the Study:

  • To investigate the role of nicotinamide adenine dinucleotide (NAD) metabolism in telomere biology disorders.
  • To explore therapeutic interventions targeting NAD homeostasis in DC.

Main Methods:

  • Analysis of NAD levels and metabolome in DC patient fibroblasts and telomerase knockout mice.
  • Assessment of CD38 NADase, poly(ADP-ribose) polymerase, and SIRT1 activities.
  • Evaluation of therapeutic effects of NAD precursor (nicotinamide riboside) and CD38 inhibition.

Main Results:

  • DC fibroblasts and telomerase knockout mice showed reduced NAD levels and altered NAD metabolome.
  • Elevated CD38 NADase and reduced poly(ADP-ribose) polymerase and SIRT1 activities were observed.
  • Supplementation with nicotinamide riboside and CD38 inhibition restored NAD homeostasis, alleviating telomere damage, mitochondrial dysfunction, and senescence.

Conclusions:

  • NAD dysregulation is a key factor in the pathophysiology of short telomere diseases.
  • Targeting NAD metabolism offers a potential therapeutic strategy for telomere biology disorders.
Keywords:
CD38 NADaseNAD metabolismmitochondrial impairmentreplicative senescencetelomere biology disorders

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