Spares NAD⁺ during DNA repair
This is where DNA damage and energy metabolism stop being separate subjects. A cell repairing a lot of damage is a cell spending a lot of NAD+, and what it spends is unavailable to everything else — the consumers genuinely compete. But the honest status here is weaker than the story usually told: the reviews report that PARP activity has been found to increase or decrease with age depending on the study. Unlike CD38, which rises reliably, PARP1 is a real consumer whose direction of travel in aging is unresolved. It belongs on the map as a mechanism, not as an explanation.
In depth
An enzyme that detects broken DNA and builds chains of poly-ADP-ribose to mark the damage for repair. Every chain is built from NAD+, so repair is paid for out of the same pool that runs the sirtuins.
What drives it
DNA integrity increases it.
Accumulating DNA damage is what activates PARP1, and each repair event draws on the NAD+ pool. This edge is why DNA damage and energy metabolism are the same problem rather than two. mechanism, not a human outcome. Chini 2024, Aging Cell, doi 10.1111/acel.13920 / PMC10776128 — NAD metabolism: role in senescence regulation and aging. doi 10.1111/acel.13920 · PMC10776128
What it drives
It reduces Cellular fuel.
Drain two. PARP1 consumes NAD+ to build poly-ADP-ribose chains during DNA repair; its Michaelis constant for NAD+ is 50-97 uM. The honest status, stated by the review itself: "PARP levels/activity have been shown to increase OR decrease depending on the study" — so unlike CD38, PARP1 is not established as a driver of the age-related decline. It is a genuine consumer whose direction of change with age is unresolved. Chini 2024, Aging Cell, doi 10.1111/acel.13920 / PMC10776128 — NAD metabolism: role in senescence regulation and aging ; Cell Metab 2019, S1550413119305029 — NAD+ in brain aging and neurodegenerative disorders. doi 10.1111/acel.13920 · PMC10776128
It reduces DNA integrity.
PARP1 detects single-strand breaks and recruits XRCC1 to execute base-excision repair. doi 10.3390/ijms140918078
It increases Calms inflammation.
PARP1 acts as a required transcriptional coactivator for NF-kB-dependent gene expression. PMID 10449410
It reduces Longevity gene.
PARP1 hyperactivation consumes the NAD+ pool that SIRT1 requires as its cosubstrate. PMID 21459330
It reduces Mitochondrial energy.
NAD+ depletion by PARP1 collapses mitochondrial ATP production in the parthanatos energetic crisis. PMID 21459330
Blends that modulate it
Each blend page names this pathway and carries the study behind its claim.
See it on the map
Open the causal map to follow this pathway upstream and downstream, arrow by arrow, each with its study.