NAD^(+)在衰老生物学中的研究进展

Research progress of NAD^(+) in the biology of aging

烟酰胺腺嘌呤二核苷酸(nicotinamide adenine dinucleotide,NAD^(+))是一种必需吡啶核苷酸,它既是氧化还原反应的经典辅酶,也是Sirtuins、聚ADP-核糖聚合酶(poly ADP-ribose polymerases,PARPs)、CD38等NAD^(+)依赖酶的共底物。NAD^(+)可直接或间接影响许多关键的细胞功能,包括能量代谢、DNA修复、细胞衰老、表观遗传和细胞内钙信号转导等,这些细胞过程和功能对于维持组织代谢稳态以及健康老龄化至关重要。在包括人类在内的多种生物中,衰老伴随着细胞和组织NAD^(+)水平的逐渐下降,而这种下降与许多老化相关疾病有因果关系,包括神经变性、代谢功能障碍、免疫失调、癌症等。研究显示补充关键的NAD^(+)前体,可以有效地恢复机体中的NAD^(+)水平,改善与年龄相关的功能缺陷。NAD^(+)代谢已成为改善老化相关疾病、延长人类健康寿命的新途径。

Nicotinamide adenine dinucleotide(NAD^(+))is an essential pyridine nucleotide that serves as a coenzyme for redox reactions and the co-substrate for NAD^(+)-dependent enzymes,including Sirtuins,poly(ADP-ribose)polymerases,and CD38.NAD^(+)can,directly and indirectly,influence many key cellular functions,including metabolic pathways,DNA repair,cellular senescence,epigenetics,and intracellular calcium signaling.These cellular processes and functions are critical for maintaining tissue and metabolic homeostasis and for healthy aging.In multiple organisms,including humans,aging is accompanied by a gradual decline in tissue and cellular NAD^(+)levels.This decline in NAD^(+)levels is linked causally to numerous aging-associated diseases,including neural degeneration,metabolic dysfunction,immune disorders,and cancer.Studies have shown that supplementation with key NAD^(+)precursors,can effectively increase NAD^(+)level of tissues that improve age-related functional deficits.Targeting NAD^(+)metabolism has emerged as a new approach to ameliorate aging-related disease and extend the human health span.