Klotho vs NAD+

Acts as a co-receptor for FGF23, regulating phosphate and vitamin D metabolism. As a circulating hormone, inhibits insulin/IGF-1 signaling to extend lifespan, activates Nrf2 antioxidant pathways, and suppresses TGF-β fibrotic signaling.

A fragment of the anti-aging Klotho protein that circulates as a hormone after ectodomain shedding. Naturally declines with age. Low Klotho levels are associated with accelerated aging, cognitive decline, cardiovascular disease, and reduced lifespan in animal models.

NAD+ is a coenzyme central to cellular energy metabolism, serving as an electron carrier in glycolysis, the citric acid cycle, and oxidative phosphorylation. It is also a required substrate for sirtuins (SIRT1–7) and PARP enzymes, which regulate DNA repair, gene expression, and mitochondrial biogenesis. NAD+ levels decline measurably with age; IV or subcutaneous delivery aims to restore intracellular pools more directly than oral precursors such as NMN or NR.

NAD+ (nicotinamide adenine dinucleotide) is a coenzyme found in every cell, central to energy production, DNA repair, and sirtuin activation. While not a peptide in the traditional sense, it is widely administered by functional medicine and longevity providers via intravenous infusion or subcutaneous injection. Research interest centres on its role in mitochondrial health, cellular resilience, and neurological function as NAD+ levels decline with age.