To me, anti-aging is simple in theory: finding a way to replenish a core set of cells (i.e., we run out of functional stem cells) and maintaining their stemness. There are multiple experiments that are consistent with this view. Experiments that increase/restore stem cells in mice, for example. Or experiments that increase telomerase. All of these experiments demonstrate increased lifespan of subject animals. What has not been clear, is what specific tissues must be targeted. Certainly, we can target ALL cells, but that does not seem rational - or is it?
NAD is interesting, because, NAD appears to be a substrate for cellular repair mechanisms. So, replenishing NAD is a bit like adding oil to ... an engine running low on oil. For example, a DNA repair mechanism (which involves PARP) works better with high NAD+ levels. SIRT1 gets expressed better, if we have more NAD+. Some stem cells d are maintained better with high levels of NAD. Furthermore, as with many repair mechanisms, NAD+ pathways are modulated in accordance with the circadian rhythm. For example, NAD+ production also follows the circadian rhythm. Nightly melatonin production leads to nightly increased activation of NAMPT, which then increases NAD generation from nicotinamide. This again reinforces the idea that NAD is a substrate for cellular repair. Note that declining NAD production as a function of age is consistent with declining melatonin levels as a function of age.
There is an argument that says: it is unlikely that replenishing NAD+ will fix the aging problem. The argument here is that changing oil is not going to fix an engine that is breaking down - which appears to be supported by experiments (shouldn't mice with high NAD levels lived very very long?). One counter argument is that NAD+ is involved in stem cell population and their stemness. According to this view, we'd only need to supply the remainder of ingredients for longevity: stimulate the stem cells to multiply (since their stemness is preserved via high NAD+), and then stimulate them to differentiate.
This latter view makes some intuitive sense. Because NAD is the substrate for repair (i.e., because it is vital in so many pathways), NAD is not in itself a signal for cellular repair. The signal has to come from somewhere else. We know, for example, that exercise leads to production of HGH and other adaptive hormones. These hormones appear to promote cellular differentiation of adult stem cells and then push them into growth. This phase of repair is clearly necessary (but automatically occur) if our bodies are to be "restored." It is intuitively clear why some of the hormone therapies appear to have such rejuvenating effect on people's appearance (e.g., muscle and body fat wise). It is interesting also, that, if we should run out of certain stem cells, these hormones should shorten the "maximal lifespan." Consider that in athletes, who presumably generate a lot of these hormones due to training, do not have the lowest mortality rates - although, their health span (or their average lifespan) is probably great.
IMO, to solve the problem, one has to first be able to regulate the correct type of stem cells. It is unclear whether replenishing telomerase (in all tissues) or NAD+ will do the trick. Telomerase may restore telomeres, but does that lead to further stem cell division (for the right stem cell type)? NAD is able to restore stemness of some cells - but do they do so for the correct tissues? IMO, NAD+ replenishment, however, probably is unlikely to solve the problem - otherwise, there should have been mice that lived really really long.
Regarding one facet of aging, hair color and stem cells - if a particular compound succeeded in stimulating critical stem cells, it should be able to affect melanocytes for hair as well. We know from NR threads that NR largely doesn't help, which seems to indicate that NAD+ is just not the right compound or that NAD+ needs a co-factor. But then, the co-factor should have eventually increased in individuals with prolonged NAD consumption. So, I have my doubts that NAD+ is the answer.
I wanted to mention an interesting treatment for generating stem cells: using hyperbaric chamber. It is said that hyperbaric oxygen chamber treament increases the number of stem cells. I will start another thread on this, but here is a link.
There is also a paper that supports the claim made in the video regarding the stem cells (by Stephen Thom). In fact, the graph of stem cell population as a function of the treatment count is from the paper.
