According to this study, the process of mitchondrial function decline, as seen in aging, creates a state of chronic hypoxia by inducing HIF-1 (which also happens to powerfully promote cancer). In fact, the following quote form the study reads like it could have been written by Ray Peat himself.
http://www.cnd.mcgill.ca/~ivan/age-reve ... mpound.pdf
"...Next, we sought to understand how SIRT1 regulates mitochondria independently of PGC-1alpha. Analysis of SIRT1 KO animals indicated that genes involved in glycolysis were upregulated, with increased lactate levels and a switch from slow-twitch oxidative fibers to fast-twitch glycolytic fibers. These metabolic changes were reminiscent of Warburg remodeling of metabolism in cancer cells, which is known to be mediated, in part, by the stabilization of the transcription factor HIF-1."
The mitochondrial decline process is mediated through falling levels of NAD+ and thus lower NAD/NADH ratio, putting the cell in a reduced state. The scientists used carolic restriction to raise NAD, which is something we know Ray does not endorse as he thinks the process will actually put the body in a stressed mode and further damage cells.
However, as we know, niacinamide raises NAD levels and thus the NAD/NADH ratio so this could be another strategy in reversing the decline in NAD and NAD/NADH.
http://www.cnd.mcgill.ca/~ivan/age-reve ... mpound.pdf
"...Next, we sought to understand how SIRT1 regulates mitochondria independently of PGC-1alpha. Analysis of SIRT1 KO animals indicated that genes involved in glycolysis were upregulated, with increased lactate levels and a switch from slow-twitch oxidative fibers to fast-twitch glycolytic fibers. These metabolic changes were reminiscent of Warburg remodeling of metabolism in cancer cells, which is known to be mediated, in part, by the stabilization of the transcription factor HIF-1."
The mitochondrial decline process is mediated through falling levels of NAD+ and thus lower NAD/NADH ratio, putting the cell in a reduced state. The scientists used carolic restriction to raise NAD, which is something we know Ray does not endorse as he thinks the process will actually put the body in a stressed mode and further damage cells.
However, as we know, niacinamide raises NAD levels and thus the NAD/NADH ratio so this could be another strategy in reversing the decline in NAD and NAD/NADH.