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A few unrelated papers caught my eye whilst winding my way through PubMed today. This first is an animal study building directly on the very rapid progress in understanding Hutchinson-Gilford progeria syndrome (HGPS), an accelerated aging syndrome.
Treatment with a farnesyltransferase inhibitor improves survival in mice with a Hutchinson-Gilford progeria syndrome mutation:
We recently reported that a protein farnesyltransferase inhibitor (FTI) improved several disease phenotypes in mice with a HGPS mutation (Lmna(HG/+)). Here, we investigated the impact of an FTI on the survival of Lmna(HG/+) mice. The FTI significantly improved the survival of both male and female Lmna(HG/+) mice. Treatment with the FTI also improved body weight curves and reduced the number of spontaneous rib fractures. This study provides further evidence for a beneficial effect of an FTI in HGPS.
This is intervening directly in the mechanisms left broken and malfunctioning by Lamin A (Lmna) mutations. You'll find a more clear explanation of the involvement of farnsylation in an earlier, similar mouse study:
Several progeroid disorders are caused by mutations that lead to the accumulation of a lipid-modified (farnesylated) form of prelamin A, a protein that contributes to the structural scaffolding for the cell nucleus. In progeria, the accumulation of farnesyl-prelamin A disrupts this scaffolding, leading to misshapen nuclei.
The point of interest to all of the rest of us in this research is that cells in the normal elderly appear to be suffering from the same issues. A working therapy for progeria is likely also a therapy of benefit to those suffering from ordinary aging processes.
Switching topics: it's often the case that studies in laboratory animals are criticized for using breeds that are far from wild-type animals, having been bred for generations in the absence of selective pression, wild-type conditions, and so forth. That is a valid criticism when dealing with complex biological systems of many variables, so it is good to see someone filling in the gaps, as in this paper:
Dietary restriction by bacterial deprivation increases life span in wild-derived nematodes:
Dietary restriction is known to promote longevity in a variety of eukaryotic organisms. Most studies of dietary restriction have been performed on animals bred for many generations under conditions that differ substantially from their natural environment, raising the possibility that some apparent beneficial effects of dietary restriction are due to adaptation to laboratory conditions. To address this question in an invertebrate model, we determined the effect of dietary restriction by bacterial deprivation on life span in five different wild-derived Caenorhabditis elegans strains and two strains of the related species Caenorhabditis remanei. Longevity was enhanced in each of the wild-derived C. elegans strains, in most cases to a degree similar to that observed in N2, the standard laboratory strain. Both strains of C. remanei were substantially longer lived any of the C. elegans isolates, produced larger brood sizes, and retained the ability to produce offspring for a longer period of time. Dietary restriction failed to increase mean life span in one C. remanei isolate, but significantly increased the maximum life span of both C. remanei strains. Thus, we find no evidence that adaptation to laboratory conditions has significantly altered the aging process in C. elegans under either standard or food-restricted conditions.
There you have it.
Switching topics once more, this last paper on the origins of osteoporosis caught my eye more for the sentiments of the researchers than for the contents:
Evolution, Aging, and Osteoporosis:
We suggest that future osteoporosis therapy will likely focus on prevention of aging in general as a means to prevent the development of osteoporosis.
I can't overemphasis how much of a sea change it is to see more of this kind of talk in the scientific community. This first decade of the 21st century is a real turning point for aging research, wherein the mainstream slowly realigns itself to to goal of healthy life extension, while the cutting edge is running ahead with the defeat of aging in mind. We live in interesting times.
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Posted by Reason
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