Anti-ageing compound set for human trials after turning clock back for mice

There has been a fair amount of research into the effects of manipulating hypoxia-inducible factor 1 (HIF-1) in lower animals, mostly nematode worms I believe. Interestingly this is one of the few manipulations in which either reducing or increasing levels of the protein in question can increase longevity. This is a sign that there is probably significant complexity involved in this outcome, such as in relationships with other mechanisms or that the effects of changes are tied to specific tissues in the body or locations within cells.

So this is, I think, an overhyping of otherwise interesting new research into a way to manipulate HIF-1 via NAD levels that is apparently an offshoot of past and ongoing research into sirtuins and aging. When considering the source of the wor - the Sinclair lab - the overhyping is perhaps less of a surprise than it might otherwise be: this is a group with a very large sunk cost behind them and little to show for it. Deep pockets nonetheless still back continued efforts, and they have a lot of experience with the press. This is a formula that leads to breathless press materials touting rejuvenation. The people who are really, actually working on rejuvenation are more restrained these days.

So I disagree with the tone of the publicity for this work; it's a great example of the mindless attention machine being manipulating into seizing on something that has little relevance compared to other far more deserving work.

I think that (a) these researchers have found an interesting set of interactions to help explain why manipulation of HIF-1 can affect longevity, and (b) the changing levels of that and various related proteins with advancing age are responses to accumulated cellular damage. Perhaps the most relevant damage is mitochondrial, given that cycling of NAD is involved in the chain of unpleasant results that unfold when mitochondrial DNA becomes damaged, or perhaps it is something else.

So to my eyes what they focus on isn't a cause, it's a consequence. The fastest way to see what causes what at this point is to work on repairing the known forms of damage rather than tracing back all of the myriad complexity of relationships and feedback loops in the cell - a task that would take substantially longer than just building means of biological repair for our cells and other small-scale structures.

Calorie Restriction for Life Extension mailing list.

There were 2.5M deaths in US in 2010: http://www.cdc.gov/nchs/fastats/deaths.htm

If you take other leading causes out (accidents 120k, diabetes 70k, influenza 50k, suicide 40k), it still leaves about 2M deaths related to ageing: heart, cancer, chronic respiratory, stroke, alzheimers.

Not a bad point, especially given that the current consensus seems to be that the agricultural revolution[1] was a net negative for most individuals in society (evidence of significant wear on the body from bending all day, evidence of worse nutrition), but it was a winning adaptation at the group level. Underscores the point that progress can make us less happy.

That said, I strongly believe that we can do anti-aging right and improve the lot of humanity.

[1] We only started needing a designated place to poop because we stayed around in one place and became numerous.

I'm 54, so I suppose I'm one of the people you have never met but still choose to label as an "old fart." Whatever.

For what it's worth, I don't care about any "balance that has existed for millions of years." I care about my life and the many people in it, whom I choose to love and respect.

As I write this, I'm recovering from a sleeve gastrectomy, where about 75% of my stomach was removed. This was voluntary on my part, to help me lose weight. I paid for it myself, out of my own pocket. My BMI last week was 36, and I've lost 12.5 pounds in the last two weeks. This morning, I walked four miles in the Seattle rain.

I did this because I love my life. It's my property, not yours. My only agreement is to respect individual rights as best I can. Don't expect me to die any sooner than I must out of some self-less concern for others.