STANFORD ó We can dye gray hair, lift sagging skin or boost lost hearing, but no visit to the day spa would be able to hide a newly discovered genetic marker for the toll that time takes on our cells. ďWeíve found something that is at the core of aging,Ē said Stuart Kim, PhD, professor of developmental biology and of genetics at the Stanford University School of Medicine.
In a study published in the July 21 issue of Public Library of Science-Genetics, Kim and colleagues report finding a group of genes that are consistently less active in older animals across a variety of species. The activity of these genes proved to be a consistent indicator of how far a cell had progressed toward its eventual demise.
Until now, researchers have studied genes that underlie aging in a single animal, such as flies or mice, or in different human tissues. However, a protein associated with aging in one species may not be relevant to the aging function in a different animal. This limitation had made it difficult to study the universal processes involved in aging.
Kimís work overturns a commonly held view that all animals, including humans, age like an abandoned home. Slowly but surely the windows break, the shingles fall off and floorboards rot, but thereís no master plan for the decay.
What we need to know: Which genes first start changing? Or which key regulatory switches start telling genes to start expressing differently? To put it more generally: What is the sequence of events that causes the genes to start behaving differently with age?
One possibility: The genes in the mitochondria (the sub-cellular organelles that generate energy molecules for the rest of the cell) could get mutated and damaged and then the genes in the nucleus start expressing differently due to signals coming out of the mitochondria.
Energy metablolism takes a big hit with age.
In the study, Kim and his colleagues looked at which genes were actively producing protein and at what level in flies and mice in a range of ages and in tissue taken from the muscle, brain and kidney of 81 people ranging in age from 20 to 80. The group used a microarray, which can detect the activity level of all genes in a cell or tissue. Genes that are more active are thought to be making more proteins.
One group of genes consistently made less protein as cells aged in all of the animals and tissues the group examined. These genes make up the cellular machinery called the electron transport chain, which generates energy in the cellís mitochondria.
Kim said the gene activity is a better indicator of a cellís relative maturity than a personís birthday. One 41-year-old participant had gene activity similar to that of people 10 to 20 years older; muscle tissue from the participant also appeared similar to that of older people. Likewise, the sample from a 64-year-old participant, whose muscles looked like those of a person 30 years younger, also showed gene activity patterns similar to a younger person.
Biopsies of many organs in your body might tell you which organs are going to wear out first and which need replacements. With the sort of biotechnology we'll have 10 or 20 years from now we'll be able to start growing replacements for the worn out parts. Ideally, the replacements could be grown inside your own body and then connected up with surgery.
You can read the full article online: Transcriptional Profiling of Aging in Human Muscle Reveals a Common Aging Signature
We analyzed expression of 81 normal muscle samples from humans of varying ages, and have identified a molecular profile for aging consisting of 250 age-regulated genes. This molecular profile correlates not only with chronological age but also with a measure of physiological age. We compared the transcriptional profile of muscle aging to previous transcriptional profiles of aging in the kidney and the brain, and found a common signature for aging in these diverse human tissues. The common aging signature consists of six genetic pathways; four pathways increase expression with age (genes in the extracellular matrix, genes involved in cell growth, genes encoding factors involved in complement activation, and genes encoding components of the cytosolic ribosome), while two pathways decrease expression with age (genes involved in chloride transport and genes encoding subunits of the mitochondrial electron transport chain). We also compared transcriptional profiles of aging in humans to those of the mouse and fly, and found that the electron transport chain pathway decreases expression with age in all three organisms, suggesting that this may be a public marker for aging across species.
People who had worse muscle function also had gene expression patterns characteristic of more aged muscles.
The authors profiled gene expression changes in the muscles of 81 individuals with ages spanning eight decades. They found 250 genes and 3 genetic pathways that displayed altered levels of expression in the elderly. The transcriptional profile of age-regulated genes was able to discern elderly patients with severe muscle aging from those that retained high levels of muscle function; that is, the gene expression profiles reflected physiological as well as chronological age.
Another use for this information: Study people on different diets and lifestyles and see if particular diets or patterns of living cause particular organs to age more rapidly.
Some day I expect spouses to include DNA tests on body aging to argue that their spouses are aging them too rapidly.
|Share |||Randall Parker, 2006 July 23 03:14 PM Aging Genetics|