NAD+ reduces age-related changes in mouse muscle

Impairment in mitochondrial homeostasis is one of the hallmarks of aging. Despite its importance underlying causes are still unclear and it is poorly understood if this process can be slowed or reversed.  Group of researchers from the USA, Portugal and Australia demonstrated importance of NAD+ in reducing age-related changes in mouse muscle. Article was published in Cell journal.

Shift from oxidative phosphorilation to anaerobic glycolisis is typical for cancer and cellular ageing. Reducing of cellular NAD+ causes imitation of hypoxia condition and disrupts sirtuins activity. Defective protein regulation and energy deficiency cause lack of tissue function, for example, reducing muscle strength.

Treatment of 22-month-old mice for 1 week with NMN, a precursor to NAD+ that increases NAD+ levels in vivo decreased accumulation of HIF-1a, reduced lactate levels; and increased ATP, COX activity, and mitochondrially encoded OXPHOS transcripts . The 22-month-old mice had increased levels of markers of muscle atrophy and inflammation compared to young wild type  mice, along with impaired insulin signaling and insulin-stimulated glucose uptake. Strikingly, treatment of old mice with NMN reversed all of these biochemical aspects of aging and switched gastrocnemius muscle to a more oxidative fiber type. However, authors did not observe an improvement in muscle strength, indicating that 1 week of treatment might not be sufficient to reverse whole-organism aging and that longer treatments might be required.