I would like to see a study to compare mTORC1, Sirt1 levels from Niagen and Rapamycin.
NAD+ is not only about energy. It is also about DNA repair and Sirtuins genes that rejuvenate your body to slow down or reverse aging.
At the end of the day, we're not concerned about the effect of an intervention on specific biochemical pathways, but on overall health and survival. So we have a much better way to assess these two agents than levels and activity of mTORC1 and SIRT1 proteins: lifespan studies.
In Zhang, Auwerx (2016), et. al. , mice administered NR at 400 mg/kg commencing at 24 months of age enjoyed "slightly increased lifespan (chow diet, mean 829 ± 12.0; NR, mean 868 ± 12.4 days, p = 0.034) (Fig. 6G)" — an increase in overall median lifespan from birth of 4.7%. The authors don't report maximum (tenth-decile) survivorship, an increase in which relative to normal, healthy controls is the sine qua non of an anti-aging intervention, but looking at the survival curves, the very last control animal died at age ≈960 days (700 days (see legend to Figure 6) + an eyeballed 260 d from the graph)), and the last treated animal died at age ≈1010 days — a similar increase of 5.2%, albeit a much dodgier figure. (And we have to question whether we can take these reported gains seriously: see the caveats on this study below).
By contrast, in the study that set off this thread, mice administered high-dose transient rapamycin treatment commencing at 23-24 months of age enjoyed overall median lifespan from birth of 16%.Again they don't report maximum LS, but "The longest-lived rapamycin-treated male in our cohort survived for 710 days post treatment to approximately 1400 days of age. Based on a survey of the literature, this is likely one of the longest-lived wild type C57BL/6 animals ever reported." This was an increase of single-animal extreme survival from birth of 13% — and without the caveats below regarding Zhang, Auwerx et al.
Caveats on Zhang, Auwerx et al.
Zhang et al paper is a good piece of work, but there are two reasons to suspect that the reported increase in lifespan (and the other outcomes) may not translate to normal, otherwise-healthy aging humans. First, it's not clear that it showed extended lifespan in any real sense: while there was a nominal difference between the two groups' median lifespans, the controls were abnormally short-lived, and the treated animals on the low side of normal. This is already clear just from looking at the shape of the survival curve itself, which is clearly not rectangular: from ≈850 days onward, both groups were clearly suffering abnormal early attrition. So this doesn't actually show an increase in LS, but rather a partial normalization of LS in a slightly short-lived colony: they limped along better for their abnormally short lives.
Second, there's the unfortunately near-universal caveat that it was done in C57BL/6J mice, who carry the NNT mutation, which makes the translatability of any study based on NAD+ repletion questionable (see also here and here for followup).
