A recent news release carried by the Longevity Meme:
http://www.longevitymeme.org/news/view_news_item.cfm?news_id=1145
http://www.sciencedaily.com/print.php?url=/releases/2004/08/040817080650.htm
... taken almost verbatim from a Mayo Clinic original:
http://www.mayoclinic.org/news2004-rst/2384.html
quite badly misrepresents the interpretation of the study to which it refers (1). The story makes it sound as if these results were important for avoiding degenerative age processes:
"Weight gain and bone thinning may seem to be natural complications of aging in humans and mice. Now, Mayo Clinic researchers have discovered a genetic basis for this physical decline."
But that isn't at all what the study shows. I have double-checked with the full text of the study and, as per the news story:
Researchers found that the mutant mice whose TLR4 was silenced had:Greater bone mineral content at 20 weeks of age compared to normal mice -- and that this relationship increased as both groups aged. Larger bones at 20-24 weeks of age. 70 percent less body fat than the control group as they grew and aged.
The body fat results, like the bone results, were measured at 6-9, 12-14, and at 20-24 weeks of age, at which point the differences were most pronounced. But 20-24 weeks of age in a mouse is roughly the equivalent of ~12-17 human years. In other words, this study is about the programmed process of development -- not the stochastic process of age-related decay.
Of course, this tells us nothing about their ability to avoid bone loss or weight gain caused by, or even associated with, aging. Indeed, one might well expect that whatever energy-intensive, likely highly mitotic process underlies this result (I'm ignorant of the TLR4 biochemistry), it might well wind up causing premature aging: think of the case of the various growth hormone/IGF1 mutant mice, or CR animals. Their bodies are smaller and scrawnier, and their bones lighter, in youth; but because they don't degenerate with age, they wind up better off in late life -- especially after all of the control animals are dead.
I guess the good news is that researchers and their institutions now want to be seen to be doing aging research.
1. Johnson GB, Riggs BL, Platt JL. A genetic basis for the "Adonis" phenotype of low adiposity and strong bones. FASEB J. 2004 Aug;18(11):1282-4. Epub 2004 Jun 18. PMID: 15208271 [PubMed - in process]
Which is why we all need fact checkers - and why you folks out there should always do your own research to supplement anything I might have to say.
TLR4 stands for Toll-like Receptor 4. It is part of the innate immune system. It binds to a component of bacterial cell walls and alerts the immune system that an infection is under way and stimulates an inflammatory response.
It is an unexpected result that these mice are healthy. They would be expected to be very susceptible to infection. However this result is consistent with the increased size and vigor of livestock grown with antibiotics which remove the bacteria that would normally stimulate this receptor.
It may be that the energy that the immune system uses when stimulated by this receptor is diverted from growth. This data further supports the hypothesis that inflammation plays a destructive role during the course of development and during aging.
Despite all of the yammering on the part of the bioethics crowd, institutions want to be seen doing anti-aging research because the boomers are getting older. This makes anti-aging research trendy. Lets hope the trendiness lasts long enough to make it happen.
Dissecting academic research is an exquisite art which I have yet to master but greatly admire.
As the signals given off by metabolically active abdominal fat seems to play a significant role in aging as demonstrated by the studies of Leonard Guarente and others, if interfering with it results in lowered levels of these signals, we might expect a healther, leaner mouse. I'm wondering as well if this result might tie in with the suggestion that caloric restriction leads to a depressed immune system?