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    Thursday, June 22, 2006

    Two Old School Studies

    A pair of studies presented at a recent neuroendocrinology conference have been doing the rounds of the science press: just the facts can be found at EurekAlert!, and an article with more commentary at the Post-Gazette. With no disrespect intended to the authors, both come across as something of a look back to the old school standard of progress prior to the bioinformatics boom: uncover a single relationship between a compound or molecule and health, then ponder on the possible significance. Nowadays, I think we're starting to expect somewhat more from research groups: metabolic pathways, complete understanding of relevant mechanisms, and the first steps towards a therapy all delivered in a nice package.

    The first of the two studies investigates the use of a growth hormone stimulator to somewhat mitigate the consequences of muscle loss with aging; as for some previous work, it found benefits:

    Aging is characterized by a progressive decline in muscle mass, strength and exercise capacity, often leading to frailty and the inability for living independently. Since growth hormone (GH) secretion also declines with age and many age-related changes resemble those seen in GH deficiency, the researchers are investigating the potential physical and endocrine effects of stimulating GH in older adults.

    In this controlled trial involving 395 men and women aged 65 to 84 with mild limitations in their physical functioning, participants received either placebo or various oral doses of the growth hormone stimulator (GHS) capromorelin ... GHS at any dose prompted an acute GH peak and an increase in overnight GH secretion – increases that were sustained throughout a 12-month treatment period. The GHS treatment also was associated with a 1.4 Kg increase in lean body (muscle) mass and an improvement in tandem (heel-to-toe) walking at 6 months and in stair climbing at 12 months.

    However, a weight of work still exists to show that there are potentially serious side effects; scientists do not yet fully understand the biochemistry and its variance between individuals. Growth hormone could have any number of unpleasant side-effects that are masked in the short term by the benefits of additional muscle, loss of fat and enabling increased exercise. Growth hormone for anti-aging use should not be illegal - for all the same reasons that taking any risk with your own body should not be illegal, providing it harms no-one else - but it's definitely a case for caveat emptor and careful research.

    Compare this with the weight of evidence for the long-term, side-effect-free benefits of exercise, losing excess fat or calorie restriction, for example. As I've noted before, growth hormone seems very much like a drug for a few specific age-related conditions - the condition in this case being a frailty that prevents the use of the three methods mentioned above to maintain health as best as possible. Like many other drugs with wide-ranging effects on metabolism, growth hormone and growth hormone stimulators are poorly characterized, poorly understood, and the research is very much in flux.

    Like calorie restriction, exercise, and losing excess fat, growth hormone therapies are short term, stop-gap measures that will not significantly extend your maximum life span - to 150 or beyond, say. No amount of tinkering with your metabolism at this level can achieve the goals of radical life extension or a defeat of aging. We must not lose sight of the fact that much more impressive technology will be needed - our primary effort should be to support the advance of suitable research to this end.

    The second study illustrates a simple relationship:

    A protein derived from fat tissue may be an important determinant of longevity, suggests a study of 133 women, including 25 aged 100 to 102, whom researchers found had notably higher levels of adiponectin circulating in their blood. Adiponectin is a peptide that has anti-inflammatory properties, helps keep vessels clear of fatty deposits and plays an important role in metabolism, particularly of lipids and glucose. Insufficient levels of adiponectin are thought to contribute to obesity, insulin resistance, diabetes or the formation of lipid deposits in the arteries, collectively known as symptoms of metabolic syndrome.

    To restate my ealier point, this is one of those results that we would nowadays expect to be accompanied by much more "how," "why" and "what this means." Correlation is not causation, and so results like this are largely fuel for speculation and little else in the absence of further investigation into the underlying biochemistry. The obvious speculation would be the same as that for the ratios of LDL and HDL cholesterol in the blood of centenarians - the people who are lucky enough to have a metabolism with this characteristic tend to live longer. Which is no great advance in knowledge - just the first sight of a long road - without an accompanying explanation as to why this might be so.

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    Posted by Reason at June 22, 2006 9:48 PM | TrackBack (0)

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