The Good, the Bad, and the Ugly of ROS: New Insights on Aging and Aging-Related Diseases from Eukaryotic and Prokaryotic Model Organisms

Figure 3

Age-dependent decline in NAD⁺. Decreased NAD⁺ synthesis and increased NAD⁺ consumption with age may both contribute to a decrease in the NAD⁺ pool. A reduction in NAD⁺ levels leads to an age-related reduction of SIRT1 activity. Reduced SIRT1 activity impacts mitochondrial function through at least two mechanisms: (1) a reduction in biogenesis secondary due to a reduction in PGC1-α activity and (2) an impairment of mitochondrial function due to a reduction in mtDNA replication and transcription. Reproduced with permission from Prolla, T.A. and Denu, J.M., 2014. NAD+ deficiency in age-related mitochondrial dysfunction. Cell Metabolism, 19(2), pp.178-180.