Nicotinamide Adenine Dinucleotide and Its Anti-aging Effects in the Context of Longevity and Menopause

Vollständiger Abstract

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Menopause is a complex biological condition associated with progressive estrogen depletion and increased susceptibility to several age-associated disorders. During this process, several biological mechanisms, such as mitochondrial dysfunction, oxidative stress, chronic inflammation, genomic instability, and immunosenescence, contribute to the progression of biological aging and metabolic imbalance. In this sense, nicotinamide adenine dinucleotide (NAD⁺) has progressively attracted attention because of its important role in mitochondrial homeostasis, DNA repair pathways, cellular energetics, and inflammatory regulation. This narrative review discusses the mechanistic relationship between NAD⁺ metabolism, aging, and menopause by integrating experimental and clinical evidence currently available in the literature. The review was developed using PubMed, Scopus, and Web of Science databases, considering studies associated with menopause, aging, NAD⁺ metabolism, nicotinamide mononucleotide (NMN), nicotinamide riboside (NR), mitochondrial dysfunction, and inflammatory signaling pathways. According to the evidence currently available, depletion of intracellular NAD⁺ levels during aging may contribute to mitochondrial dysfunction, impaired metabolic regulation, chronic inflammatory signaling, and neurodegenerative alterations. Although NAD⁺ precursors such as NMN and NR have shown promising biological effects in experimental studies, some limitations are still evident when these findings are translated to humans, including pharmacokinetic instability, tissue-specific bioavailability, and variability in clinical responses. Moreover, chronic inflammation and CD38 overexpression appear strongly associated with progressive intracellular NAD⁺ depletion during aging and menopause. Thus, modulation of NAD⁺ metabolism may represent a promising strategy in longevity medicine and menopausal health. However, despite the important mechanistic advances achieved in recent years, long-term clinical evidence is still insufficient to support a definitive therapeutic conclusion. Therefore, more experimental and clinical studies are still required to establish the real therapeutic relevance and safety of NAD⁺-targeted interventions in menopausal women.