Energy balance
Hyperactivation of PARP1 due to persistent DNA damage depletes cellular NAD+, which inhibits SIRT1 activity and leads to mitochondrial dysfunction, thereby accelerating aging and neurodegeneration.
Chronic DNA damage can drain your cells' energy resources (NAD+) by forcing them to constantly repair DNA. This impairs mitochondrial function. Strategies that support NAD+ levels (like exercise or potentially specific supplements, though not explicitly dosed here) might help mitigate this drain, but the primary goal is minimizing DNA damage.
Hyperactivation of PARP1 is associated with aging, abnormal metabolism, neurodegeneration... The side effects of PARP1 hyperactivation may be partially attributed to a reduction of the NAD+-SIRT1 pathway because both PARP1 and SIRT1 compete for NAD+.
Why this rating
Supported by mouse models (PARP1 KO), C. elegans studies, and human cell lines (XPA, CS).
Source
DNA Damage, DNA Repair, Aging, and Neurodegeneration
Scott Maynard et al. · Cold Spring Harbor Perspectives in Medicine · 2015
DOI 10.1101/cshperspect.a025130
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