Wednesday, August 13, 2008

Aging Biomarkers plus Importance of Lysosomes

Researchers are looking for biomarkers which would reveal the state of aging in an organism. Given the relationship between telomere length and cell reproductive capacity, researchers at Rockefeller University looked for biomarkers of telomere shortening.
Telomere dysfunction limits the proliferative capacity of human cells by activation of DNA damage responses, inducing senescence or apoptosis. In humans, telomere shortening occurs in the vast majority of tissues during aging, and telomere shortening is accelerated in chronic diseases that increase the rate of cell turnover. Yet, the functional role of telomere dysfunction and DNA damage in human aging and diseases remains under debate. Here, we identified marker proteins (i.e., CRAMP, stathmin, EF-1α, and chitinase) that are secreted from telomere-dysfunctional bone-marrow cells of late generation telomerase knockout mice (G4mTerc−/−). The expression levels of these proteins increase in blood and in various tissues of aging G4mTerc−/− mice but not in aging mice with long telomere reserves. _PNAS_via_NBF
It will be interesting to determine if the same markers are present in humans.

Scientists at Albert Einstein College of Medicine have managed to "stop the aging process" by boosting cellular protein clearance.
"Many of these diseases [of aging AF] are due to 'misbehaving' or damaged proteins that accumulate in neurons. By preventing this decline in protein clearance, we may be able to keep these people free of symptoms for a longer time."

If the body's ability to dispose of cell debris within the cell were enhanced across a wider range of tissues, she says, it could extend life as well.

In healthy organisms, a surveillance system inside cells called chaperone-mediated autophagy (CMA) locates, digests and destroys damaged proteins...Specialised molecules, the "chaperones", ferry the harmful material to membrane-bound sacs of enzymes within the cells known as lysosomes...Once the cargo has been "docked", a receptor molecule transfers the protein into the sac, where it is rapidly digested.

With age, these receptors stop working as well, resulting in a dangerous build-up of faulty proteins that has been linked, in the liver, to insulin resistance as well as the inability to metabolise sugar, fats or alcohol.

The same breakdown of the cell's cleaning machinery can also impair the liver's ability to remove the toxic build-up of drugs at a stage in life when medication is often part of daily diet.

In genetically modified mice, Cuervo compensated for the loss of the receptors in the animals by adding extra copies...."That was enough to maintain a clean liver and to prove that if you keep your cells clean they work better," she says. _Source_via_NextBigFuture
Cleaning up cellular debris buildup is part of Aubrey de Grey's SENS program of engineered anti-senescence.

Anti-aging research proceeds along several fronts. It is important to be able to monitor a person's state of aging, if anti-aging therapy is to be put upon a sound scientific basis. And it is vital to produce many safe and effective therapies against as wide a range of aging mechanisms as possible.


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