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


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.

SUBMITTER: McReynolds MR 

PROVIDER: S-EPMC8678178 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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NAD<sup>+</sup> is an essential coenzyme for all living cells. NAD<sup>+</sup> 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<sup>+</sup> metabolism across tissues. In aged mice, we observed modest tissue NAD<sup>+</sup> depletion (median decrease ∼30%). Circulating NAD<sup>+</sup> precursors were not significantly changed, and isotope  ...[more]

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