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Pathway Description
NAD+ Signalling and Aging
Homo sapiens
Signaling Pathway
Created: 2018-08-08
Last Updated: 2019-08-16
An interesting link has emerged between NAD+ metabolism, SIRT1, SIRT3, and mitochondrial function. NR and PARP inhibitors increased life span in worms via activation of the mitochondrial unfolded protein response UPRmt by sir2.1. Short-term (1 week) supplementation of these mice with NMN restored mitochondrial homeostasis in muscles, which suggests that NAD+ supplementation can restore some reversible aspects of the aging process. Both observations are consistent with the model indicating that an imbalance in the relative stoichiometries of mitochondria- versus nucleus-encoded ETC proteins may induce life-span extension via activation of the UPRmt. In support of such a mechanism, mutation or reduced function in nuclear genes encoding ETC components in yeast, Caenorhabditis elegans, Drosophila, and mice increase life span through activation of the mitochondrial unfolded protein response UPRmt. NAD salvage pathway is deficient in aging since the supplementation with NMN corrects defects associated with aging.
References
NAD+ Signalling and Aging References
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