Some reading matter, light and not so light, for you folk today - while the interest bubble blooms for the calorie restriction mimetic compound resveratrol. First some comments from an Immortality Institute thread:

We do not know how it will perform in humans, but when was the last time we saw another "Resveratrol" in the past? Has there been other substances which have received as much attention in research for anti-aging application such as resveratrol?

...

The only one that comes close is HRT (hormone replacement therapy). It was widely accepted until the long term studies came out. I hope and believe that reveratrol will have a happier ending. Time will tell.

A good reminder that patience hurts little, given the present breakneck pace at which research is moving forward. Jumping into the fast boat carries certain risks; if you're really interested in obtaining these sorts of health benefits in the near future, it seems to me you should first look into the practice of calorie restriction rather than the drug pipeline.

On to the scientific papers; via the GRG list, Robert Bradbury notes:

Apparently Cell isn't clever enough to do direct upload abstracts into PubMed (unlike perhaps Nature & Science???) so the abstract isn't in PubMed yet. But in a rare(?) display of public seduction by a closed source journal they have made the full article PDF generally available [1]. The URL for the most recent Sinclair reference is [2]. It unfortunately does not appear to be available to the public.

As a side note, PubMed reports that there are now 1646 references now for resveratrol -- so going through the literature is not exactly a walk in the park. Though the papers involving resveratrol and Sirtuins and related genes ( i.e. the regulatory pathways) are only currently ~30-40 so at least that aspect can be managed.

1. http://images.cell.com/images/EdImages/cell/lagouge.pdf
(This really works, I'm looking at the PDF in Adobe Reader right now on my screen and I'm quite positively shocked.)

2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=17086191

Worth reading if you are familiar with the present state of thought with regard to metabolism and longevity; the interesting question to me is to what degree all of this genetic and biochemical process manipulation via diet, drugs and other methodologies will be found to boil down to effects on a few core processes. Such as, say, the effects of fat and inflammation, or the insulin pathways. To put it another way, how much of the benefit of calorie restriction stems from lacking fat, how much from low levels of inflammation, and so forth?

I don't think we'll be left hanging for too many more years insofar as answers to these sorts of questions go. Metabolic manipulation may not be the most efficient path forward for healthy life extension, but it's most interesting to see answers, understanding and further questions in equal measure starting to flow thick and fast.

Moving on, Randall Parker put up some thoughts and links on all this resveratrol work:

It would be hard to get regulatory approval for a drug that increased life expectancy because it is a claim that is hard to prove in a clinical trial. But Sitris is chasing a more provable claim: That their modified resveratrol molecule, SRT501, will reduce the symptoms of old age and obesity such as high unhealthy blood lipids and insulin resistance in the form of type II diabetes.

...

Back in March 2005 Sirtris co-founder David Sinclair of Harvard said that most commercial resveratrol preparations have no active resveratrol in them - with activity measured by the ability to activate the SIR2 enzymes.

...

Bulk sources of resveratrol from knotweed can be found on the internet. But which of those sources is selling real active resveratrol? Your guess is as good as mine.

Then there's the question of whether this stuff is safe. We do not know. Okay? Really, we do not know. We need a big study of large numbers of people taking a gram of resveratrol a day with all sorts of checks done on them to look for bad signs. My guess is we are not going to see such a study on resveratrol because the money is in making a patentable commercial variation of resveratrol into a marketable drug. That'll take 6, 7, 8 years more and hundreds of millions of dollars.

He goes on to make much the same point as I have been making - that slowing aging by manipulating metabolism is a comparative waste of resources if we don't also devote serious effort to reversing aging through repair of age-related cellular damage, such as is proposed in the Strategies for Engineered Negligible Senescence.

The resources exist to do both - but I can tell you that from the high level view, in comparison to, say, the cancer or AIDS research establishment, even metabolic manipulation is barely funded. From the high level point of view, work to repair and reverse aging isn't even on the radar. This must all change - we must make this all change - over the next decade if we are to have a shot at far longer, healthier lives. Unless we act soon to build infrastructure and a research community, we will not live to see significant progress in human longevity.

Technorati tags: biotechnology, calorie restriction, life extension, resveratrol

Posted by Reason at November 19, 2006 5:29 PM | TrackBack (0)