NAD+ flux is maintained in aged mice despite lower tissue concentrations

Melanie R. McReynolds, Karthikeyani Chellappa, Eric Chiles, Connor Jankowski, Yihui Shen, Li Chen, Hélène C. Descamps, Sarmistha Mukherjee, Yashaswini R. Bhat, Siddharth R. Lingala, Qingwei Chu, Paul Botolin, Faisal Hayat, Tomohito Doke, Katalin Susztak, Christoph A. Thaiss, Wenyun Lu, Marie E. Migaud, Xiaoyang Su, Joshua D. RabinowitzJoseph A. Baur

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

NAD+ is an essential coenzyme for all living cells. NAD+ concentrations decline with age, but whether this reflects impaired production or accelerated consumption remains unclear. We employed isotope tracing and mass spectrometry to probe age-related changes in NAD+ metabolism across tissues. In aged mice, we observed modest tissue NAD+ depletion (median decrease ∼30%). Circulating NAD+ precursors were not significantly changed, and isotope tracing showed the unimpaired synthesis of nicotinamide from tryptophan. In most tissues of aged mice, turnover of the smaller tissue NAD+ pool was modestly faster such that absolute NAD+ biosynthetic flux was maintained, consistent with more active NAD+-consuming enzymes. Calorie restriction partially mitigated age-associated NAD+ decline by decreasing consumption. Acute inflammatory stress induced by LPS decreased NAD+ by impairing synthesis in both young and aged mice. Thus, the decline in NAD+ with normal aging is relatively subtle and occurs despite maintained NAD+ production, likely due to increased consumption.

Original languageEnglish (US)
Pages (from-to)1160-1172.e4
JournalCell Systems
Volume12
Issue number12
DOIs
StatePublished - Dec 15 2021

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine
  • Histology
  • Cell Biology

Keywords

  • CD38
  • NAD
  • NADH
  • PARP
  • PARP1
  • SIRT1
  • aging
  • flux
  • mononucleotide
  • niacin
  • nicotinamide
  • redox
  • riboside
  • sirtuins

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