A Potent and Specific CD38 Inhibitor Ameliorates Age-Related Metabolic Dysfunction by Reversing Tissue NAD(+) Decline

Tarragó MG, Chini CCS, Kanamori KS, Warner GM, Caride A, de Oliveira GC · Cell Metabolism

Blocking the NAD+-consuming enzyme CD38 with 78c reversed tissue NAD+ decline in aged mice and improved glucose tolerance, exercise capacity (a near-doubling of maximal distance run and work performed, with time to exhaustion about 30 per cent longer at two years old), muscle architecture and cardiac function; survival rose in a separate progeroid model. Three-month-old mice gained nothing and their NAD+ did not move. Both the glucose and the exercise benefit were abolished by co-administering an inhibitor of NAD+ synthesis, tying them to NAD+ itself.

Population

Naturally aged and progeroid mice

Intervention

78c, a specific CD38 inhibitor

Comparator

Vehicle

Limitations

Mouse only; 78c is an experimental compound, not a supplement. It shows that blocking NAD+ consumption works in mice, which is a different intervention from taking a precursor. Supported in part by a grant from a longevity biotechnology company, with the inhibitor supplied by that company and by the pharmaceutical company that originated it, and one author employed by a pharmaceutical firm.