Silkworm as a model for NAD⁺-dependent lifespan regulation: Functional insights into BmNmnat1 and nicotinic acid

Nicotinamide adenine dinucleotide (NAD⁺) is a central metabolic coenzyme that regulates redox homeostasis, DNA repair, and cellular longevity. While the role of NAD⁺ metabolism in mammalian aging has been well studied, its significance in invertebrate systems remains underexplored. Here, we establish the silkworm (Bombyx mori) as a novel model for investigating NAD⁺-dependent lifespan regulation. Through phenotypic comparisons among silkworm strains, we found that longer-lived strains exhibit higher levels of NAD⁺ and elevated expression of BmNmnat1, a key enzyme in NAD⁺ biosynthesis. CRISPR/Cas9-mediated knockout and RNAi knockdown of BmNmnat1 led to embryonic lethality, increased DNA damage, disrupted cell cycle progression, and morphological aging phenotypes. Supplementation with nicotinic acid (NA) significantly reversed these aging-associated changes both in vitro and in vivo, including improved redox balance, reduced oxidative stress markers, and prolonged adult lifespan. Our results highlight the evolutionarily conserved role of BmNmnat1-mediated NAD⁺ metabolism in aging and establish the silkworm as a valuable invertebrate model for mechanistic studies and antiaging intervention screening.