Fight Aging!

Let me open by saying that I rarely talk about supplements except to trash them. This is because (a) there are already plenty of people out there talking about nothing but supplements, and (b) there's no scientific evidence that demonstrates the sort of heavy-duty supplement packages advocated today to produce health and longevity benefits in any way comparable to those attained by exercise and calorie restriction. If you're fat and sedentary and you're feeling virtuous because you're taking expensive dietary supplements, you're most likely going to be disappointed in the trajectory of your future health.

Anyway. Today we're going to talk about melatonin because it looks like it triggers the sirtuin SIRT1 in a similar way to resveratrol, and a number of people are interested in following sirtuin research. You might recall that researchers presently believe SIRT1 to work by affecting heat shock proteins and thereby making cellular repair processes more efficient. This research is itself an outgrowth of calorie restriction studies, and it's worth reminding everyone that resveratrol itself hasn't been shown to produce any health benefit that is as effective as calorie restriction. On that basis, a number of researchers are looking elsewhere for the controlling mechanisms of calorie restriction.

Sirtuins remain interesting, however, given that they are connected to all sorts of triggers and switches inside metabolism that relate to longevity, cancer, energy generation, and so forth. Calorie restriction demonstrates that noteworthy benefits can be achieved through manipulation of these controls - the question is whether there is an even better setting that could be attained through drugs or gene manipulation, a setting that slows down aging further than calorie restriction.

A perhaps more pertinent question is whether that better metabolism can be developed and made commercially available before those of us reading this now get old. That's where I have my doubts, and think we'd all be better off if the research community focused more on SENS-like repair strategies and less on slowing down aging by manipulation of metabolism. Slowing aging is a wash if you're already old by the time the medical technology to achieve that goal arrives. Repairing the damage of aging on the other hand...

In any case, here's the paper that caught my eye today, published in the Journal of Pineal Research. A brief scan of past issues suggests this might as well be called the Journal of Melatonin Studies and Nothing Else. I'm impressed - or possibly appalled, I can't decide which - that we live in an age in which a research community exists that can reliably fill a bi-monthly journal with nothing but studies of melatonin:

Sirtuin 1 is a member of the sirtuin family of protein deacetylases, which have attracted considerable attention as mediators of lifespan extension in several model organisms. Induction of sirtuin 1 expression also attenuates neuronal degeneration and death in animal models of Alzheimer's disease and Huntington's disease.

In this study, an in vitro model of neuronal aging was used to test in several ways whether melatonin acts as a sirtuin 1 inducer and if this effect could be neuroprotective. It is shown that melatonin is able to increase the level of this deacetylase in young primary neurons, as well as in aged neurons. We also observed an increase in the deacetylation of several substrates of sirtuin 1, such as p53, PGC-1alpha, FoxO1, ADAM10 and NFkappaB.

Over the past years, you've probably seen all of those substrate genes mentioned here or in the Longevity Meme News. The biochemistry of metabolism is a tangled mess of a machine, and nothing operates independently. All of these genes and the mechanisms they participate in are legitimate areas of study until someone finally sorts it all out with a verifiable grand unified theory of metabolic mechanisms.

Tajes, M., Gutierrez-Cuesta, J., Ortuño-Sahagun, D., Camins, A., & Pallàs, M. (2009). Anti-aging properties of melatonin in an in vitro murine senescence model: involvement of the sirtuin 1 pathway Journal of Pineal Research DOI: 10.1111/j.1600-079X.2009.00706.x