In lieu of any more coherent message, I though I'd point out some items of interest that attracted my attention today. They all illustrate the great long term value inherent in understanding of biochemical mechanisms; we are at the stage now where understanding can quickly lead to therapies and potential cures for those conditions with more straightforward causes. One might even argue that, given enough progress and knowledge, all causes become straightforward. The moon and stars were mysteries until they were not; the same is true of the detailed molecular workings of our bodies.
Werner syndrome (WS) is a premature aging disorder used as a model of normal human aging. WS individuals have several characteristics of normal aging, such as cataracts, hair graying, and skin aging, but manifest these at an early age. Additionally, WS individuals have high levels of inflammatory diseases, such as atherosclerosis and type 2 diabetes. The in vivo aging in WS is associated with accelerated aging of fibroblasts in culture. The cause of the accelerated senescence is not understood, but may be due to the genomic instability that is a hallmark of WS. Genome instability results in activation of stress kinases, such as p38 ... The recent development of p38 inhibitors with different binding properties, specificities, and oral bioavailability [will] make it possible to dissect the roles of various kinase pathways in the accelerated senescence of WS cells. If this accelerated senescence is reflective of WS aging in vivo, these kinase inhibitors may well form the basis of antiaging therapies for individuals with WS.
As has been observed for progeria, Werner syndrome appears to result from one contributing mechanism of normal aging grown wild and exaggerated. As for progeria, it seems plausible that therapies for Werner syndome will have at least some value for those of us fortunate to "only" be aging normally.
Reactive oxygen species (ROS) damage biomolecules, accelerate aging, and shorten life span, whereas antioxidant enzymes mitigate these effects. Because mitochondria are a primary site of ROS generation and also a primary target of ROS attack, they have become a major focus area of aging studies. Here, we employed yeast genetics to identify mitochondrial antioxidant genes that are important for replicative life span.
Of the ten known genes, only three made much difference - interesting. If you want to bioengineer mitochondria to produce more antioxidants of those types already produced, it makes sense to focus on those that make the most difference. Small steps on a long road ahead.
Alzheimer's disease, Parkinson's disease, type II diabetes, the human version of mad cow disease and other degenerative diseases are more closely related at the molecular level than many scientists realized ... Harmful rope-like structures known as amyloid fibrils, which are linked protein molecules that form in the brains of patients with these diseases, contain a stack of water-tight "molecular zippers," the scientists report.
"We have shown that the fibrils have a common atomic-level structure," said David Eisenberg, director of the UCLA-Department of Energy Institute of Genomics and Proteomics, a Howard Hughes Medical Institute investigator and a member of the research team. "All of these diseases are similar at the molecular level; all of them have a dry steric zipper. With each disease, a different protein transforms into amyloid fibrils, but the proteins are very similar at the atomic level."
The research, while still preliminary, could help scientists develop tools for diagnosing these diseases and, potentially, for treating them through "structure-based drug design," said Eisenberg, a UCLA professor of chemistry and molecular biology.
Drug design will increasingly become a matter of molecule design in the years ahead. Researchers are looking for atomic-scale glue, levers, patches and prybars to pick apart, block or reshape disease-causing arrangements of molecules - which of course requires a good knowledge of what all these molecules are actually doing in the first place. Aging itself is nothing more than an undesirable rearrangement of molecules; if we want to effectively deal with aging, then we're going to have to become very good at this sort of thing.