NAD+ glycohydrolases-CD38 as a therapeutic target in aging: physiological roles, molecular mechanisms, and future opportunities in anti-aging research

Abstract

As individuals age, tissue homeostasis and functionality gradually deteriorate, leading to the occurrence and advancement of age-related illnesses. Nicotinamide adenine dinucleotide (NAD⁺) is essential for metabolism and cellular energy generation. The significance of maintaining adequate the levels of NAD⁺ within biological systems to ameliorate age-related tissue degeneration and prevent age-related illnesses in senescent animals is now widely recognized, emphasizing the importance of increasing NAD⁺ levels. Cluster of differentiation 38 (CD38), a multifunctional enzyme, plays a significant role in maintaining the cellular equilibrium of NAD⁺ through the consumption of NAD⁺. Recent research has shown a correlation between aging and upregulation of CD38 expression, potentially resulting in a reduction in NAD⁺ with increasing age. In contrast, the lack of CD38 has been shown to have a beneficial effect on slowing the aging process. Consequently, CD38 has been increasingly identified as a potential therapeutic target for interventions aimed at combatting aging. This study investigated the physiological roles of CD38, its ramifications in the aging process, possible molecular mechanisms associated with its involvement in aging-related diseases, and possible therapeutic applications of small-molecule inhibitors targeting CD38 in the context of aging. In this review, we provide a comprehensive analysis of the potential applications and future opportunities of CD38 in anti-aging research.

Keywords: Aging; Anti-aging regulatory target; CD38; CD38 small-molecule inhibitors; Nicotinamide adenine dinucleotide.