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NAD + Flux and Resiliency in Aged Mice
Author(s) -
McReynolds Melanie R.
Publication year - 2022
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2022.36.s1.r6281
Subject(s) - nad+ kinase , nicotinamide , cofactor , metabolism , chemistry , biochemistry , calorie restriction , nicotinamide phosphoribosyltransferase , endocrinology , medicine , biology , enzyme
NAD + is an essential coenzyme found in all living cells. NAD + concentrations decline during aging, but whether this reflects impaired production or accelerated consumption remains unclear. Here we employed isotope tracing and mass spectrometry to probe NAD + metabolism across tissues in aged mice. In 25‐month‐old mice, we observe modest tissue NAD + depletion (median decrease ~30%) without significant changes in circulating NAD + precursors. Isotope tracing showed unimpaired synthesis of circulating nicotinamide from tryptophan, and maintained flux of circulating nicotinamide into tissue NAD + pools. Although absolute NAD + biosynthetic flux was maintained in most tissues of aged mice, fractional tissue NAD + labeling from infused labeled nicotinamide was modestly accelerated, consistent with increased activity of NAD + consuming enzymes. Long‐term calorie restriction partially mitigated age‐associated NAD + decline despite decreasing NAD + synthesis, suggesting that calorie restriction reduces NAD + consumption. Acute inflammatory stress induced by LPS decreased NAD+ by impairing synthesis in both young and aged mice. Thus, age‐related decline in NAD + is relatively subtle and driven by increased NAD + consumer activity rather than impaired production.