age related changes in nad+ metabolism oxidative stress and sirt1 activity in wistar rats年龄相关的变化nad + wistar鼠代谢氧化应激和sirt1的活动.pdfVIP

Age Related Changes in NAD+ Metabolism Oxidative Stress and Sirt1 Activity in Wistar Rats 1 1,2 3 3 4 1,5 Nady Braidy , Gilles J. Guillemin , Hussein Mansour , Tailoi Chan-Ling , Anne Poljak , Ross Grant * 1 Department of Pharmacology, School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, Australia, 2 St Vincent’s Centre for Applied Medical Research, Sydney, Australia, 3 Retinal and Developmental Neurobiology Lab, Discipline of Anatomy and Histology, School of Medical Sciences, University of Sydney, Australia, 4 Bioanalytical Mass Spectrometry Facility, University of New South Wales, Sydney, Australia, 5 Australasian Research Institute, Sydney Adventist Hospital, Sydney, Australia Abstract The cofactor nicotinamide adenine dinucleotide (NAD+) has emerged as a key regulator of metabolism, stress resistance and longevity. Apart from its role as an important redox carrier, NAD+ also serves as the sole substrate for NAD-dependent enzymes, including poly(ADP-ribose) polymerase (PARP), an important DNA nick sensor, and NAD-dependent histone deacetylases, Sirtuins which play an important role in a wide variety of processes, including senescence, apoptosis, differentiation, and aging. We examined the effect of aging on intracellular NAD+ metabolism in the whole heart, lung, liver and kidney of female wistar rats. Our results are the first to show a significant decline in intracellular NAD+ levels and NAD:NADH ratio in all organs by middle age (i.e.12 months) compared to young (i.e. 3 month old) rats. These changes in [NAD(H)] occurred in parallel with