Everyone talks about NAD+ like it's just an energy molecule. It's also doing something way more specific in DNA repair.
I keep seeing NAD+ described as "cellular energy currency" and leaving it there, which honestly undersells what's going on. There's a specific enzyme relationship here that doesn't get mentioned enough.
PARP1 is the protein that shows up first when DNA gets a double-strand break. It uses NAD+ directly as a substrate to build these poly-ADP-ribose chains that basically flag the damage site so the rest of the repair crew knows where to go. That part's pretty well known.
What's less talked about is that SIRT6, which is itself an NAD+-dependent enzyme, is what activates PARP1 in the first place. Mao et al. found that SIRT6 physically attaches to PARP1 and modifies it in a way that ramps up its repair activity under oxidative stress (Science, 2011, PMID 21680843). So you've got NAD+ needed twice in the same chain of events, once to power the enzyme that turns the system on, and again to fuel the repair enzyme itself.
That's probably part of why NAD+ decline gets treated as a bigger deal than a simple "less fuel in the tank" story. You're not just running low, you're losing the thing that activates the activator.
Wrote up the fuller mechanism (base excision repair, where SIRT6 fits, the whole chain) here if anyone wants to go deeper: https://spartanpeptides.com/blog/nad-plus-dna-repair/
Research use only obviously. Curious if anyone's seen good independent replication on the SIRT6-PARP1 interaction outside the original Mao paper, that's the piece I haven't dug into yet.