CD38‐Targeting Peptide Vaccine Ameliorates Aging‐Associated Phenotypes in Mice

Antiaging vaccines have recently been found to elicit long-term benefits in slowing the aging process. Meanwhile, high CD38 expression in organs is an aging characteristic contributing to a decreased NAD⁺/NADH ratio. Thus, in the current study, we systematically investigate the effects of a CD38-targeting peptide vaccine (CD38-vaccine) on aging-associated phenotypes in mice. The CD38-vaccine induces a robust T-cell immune response, selectively depletes CD38⁺ myeloid cells in the spleen, and ameliorates age-related physical and cognitive function decline. Metabolically, vaccination improves glucose tolerance, enhances oxygen consumption, and decreases the number of senescent cells and mRNA levels of senescence-related genes in liver tissues. Vaccination also increases the NAD⁺/NADH ratio in the liver tissues, enhances oxidative metabolism, and reduces glycolysis. These findings indicate that targeting CD38 via vaccination is a promising strategy for ameliorating aging-associated phenotypes.