# PARP1

PARP1 (poly(ADP-ribose) polymerase 1) is a nuclear enzyme. It is a central sensor of DNA damage, especially single-strand breaks. When activated, it cleaves NAD+. Then it transfers ADP-ribose units onto itself and onto other proteins, building branched 'poly(ADP-ribose)' (PAR) chains. Those PAR signals recruit base-excision-repair factors, reshape chromatin, and coordinate the early DNA-damage response. But PARP1 burns through a lot of NAD+. So in aging tissues, where DNA damage piles up, chronic or excessive PARP1 activity can drain your cellular NAD+. That, in turn, lowers the activity of NAD+-dependent enzymes like the sirtuins, and impairs mitochondrial function. So the NAD+-PARP1-sirtuin axis is a central hub. It links genome maintenance, energy metabolism, and aging. And it is a target for NAD+ precursor and PARP inhibitor strategies.

## Sources

- Verdin E. (2015). NAD+ in aging, metabolism, and neurodegeneration. Science. https://doi.org/10.1126/science.aac4854
- Bürkle A, Virag L. (2013). Poly(ADP-ribose): PARadigms and PARadoxes. Molecular Aspects of Medicine. https://doi.org/10.1016/j.mam.2012.12.010
- Covarrubias AJ, Perrone R, Grozio A, Verdin E. (2021). NAD+ metabolism and its roles in cellular processes during ageing. Nature Reviews Molecular Cell Biology. https://doi.org/10.1038/s41580-020-00313-x

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_Canonical: https://longevity-switzerland.com/en/glossary/parp1 · Part of Longevity Cities · Updated 2026-06-22_