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NAD+ and NADPH levels in muscle correlate with function more than with age
On 28 August the authors of a preprint measured six metabolism‑related compounds in muscle biopsies from 137 men aged 20–93 years. Total NAD(H) and NADP(H) pools showed no significant age‑related change.
After adjusting for age, NAD+ remained associated with walking speed, leg power, muscle mass and mitochondrial count; NADPH retained links to walking, leg power, muscle mass, mitochondrial respiration and mitochondrial number. NAD+ fuels energy‑producing reactions, while NADPH supports biosynthesis and glutathione regeneration.
Both glutathione forms rose with age in parallel, keeping their ratio stable. To test whether the NAD(P) links reflected mitochondrial quantity or respiratory capacity, the authors used citrate‑synthase activity as a mitochondrial‑number marker. NAD+ and NADPH correlated with both citrate‑synthase activity and maximal respiration; when respiration was normalized to citrate‑synthase activity, the associations disappeared, indicating mitochondrial number as the proximate explanation.
The authors note that 2022 study data had shown lower NAD+ in older adults, especially those with poorer physical performance, whereas trained older adults approached youthful levels. A May analysis of NAD+ in whole blood across seven human cohorts also found little age‑related change. They conclude that NAD(P) exchange metrics better reflect preserved muscle health than aging, and that NAD‑modulating interventions should be evaluated by corresponding tissue‑specific functional outcomes.
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