NAD+ in Aging, Metabolism, and Neurodegeneration

The Study
A 2015 review from the Gladstone Institutes at the University of California, San Francisco, published in Science — one of the world's most cited peer-reviewed journals. Author Eric Verdin examines NAD⁺ biology across aging, metabolism, and neurodegeneration, synthesizing findings from over 100 studies on NAD⁺ decline and supplementation.

Key Findings

NAD⁺ declines significantly with age
Cellular NAD⁺ concentrations decrease during aging and senescence across multiple tissues — including skeletal muscle, white adipose tissue, and the pancreas. This decline is driven by decreased synthesis via the NAD⁺ salvage pathway and increased consumption by DNA-repair enzymes (PARPs) as damage accumulates with age.

NAD⁺ governs mitochondrial function and energy production
NAD⁺ is essential for mitochondrial intermediary metabolism. Decreased NAD⁺ concentrations impair sirtuin activity (SIRT1, SIRT3), leading to defective mitochondrial biogenesis, reduced oxidative phosphorylation, and accelerated metabolic decline — all hallmarks of biological aging.

Restoring NAD⁺ levels reverses markers of aging
Short-term NAD⁺ precursor supplementation restored mitochondrial homeostasis in aged muscle tissue. NAD⁺ supplementation also extended lifespan in yeast and worms, and protected against metabolic syndrome, neurodegeneration, and DNA repair defects in animal models.

Verdin, E. | Science | Vol. 350, Issue 6265 | December 2015 | Gladstone Institutes, UCSF

Read the full journal: https://pubmed.ncbi.nlm.nih.gov/26785480/