Tropes

R_www.asianscientist.com 2015 00022.txt.txt

#Telomeres Implicated In Premature Aging Scientists have established successfully a comprehensive model of rare accelerated aging disorder, Hutchinson-gilford progeria syndrome (HGPS), opening up the possibility of treatment for the rare disease. Their work, published in elife, also sheds light on the mechanisms of aging and human health. HGPS is an extremely rare genetic disease which causes patients to start aging rapidly when they are around one year old. Symptoms include stunted growth and joint abnormalities, and patients often die of heart failure by their teenage years. One in four million children suffer from HGPS, which currently has no effective treatment. The syndrome is caused by a mutated protein called progerin which induces DNA damage, triggers premature cellular aging and slows down cell proliferation, resulting in accelerated aging. It was thought previously that progerin did so through causing the nucleus to be deformed, thereby weakening the ability of cells to divide and proliferate. But there is more to HGPS than meets the eye. This study proposes a radically different model, in which progerin is linked to telomeresepetitive DNA sequences that protect the ends of human chromosomes and shorten each time a cell divides, limiting a cell's regenerative capacity. Progerin induces a reduction in heterochromatin, a tightly packed form of DNA making telomeres in the cell more fragile and susceptible to damage. The damaged telomeres in turn trigger premature cellular aging. While a few studies had reported that telomerase appeared to rescue progerin-induced DNA damage, no study thus far had provided conclusive evidence or elucidated the underlying reasons. The study now demonstrates that telomeres are indeed closely related to HGPS and explained why. The researchers found that adding the enzyme telomerase, which elongates telomeres, comprehensively counteracted the effects of progerin through preventing proliferative defects, DNA damage, and gene expression differences induced by progerin. However, telomerase could not rescue the loss of heterochromatin. It was further found that while increasing the protein LAP2ALPHA impaired the proliferation of normal cells, the same increase was instead able to pull up heterochromatin levels in progeric cells to match that of normal cells, thus preventing telomere damage in the first place. Taken together, the study reveals that LAP2ALPHA plays a key role in HGPS. These findings may open new avenues for the clinical treatment of HGPS patients. Therapies incorporating LAP2ALPHA may be administered to early-diagnosis HGPS patients to minimise telomere damage, while older patients, who have undergone already telomere damage, may be provided with telomerase enhancing treatments to elongate their telomeres. Treating HGPS patients holistically with both LAP2ALPHA and telomerase would thus counteract the effects of progerin on cellular aging, and greatly increase their chances of survival past their teenage years. Furthermore, the study showed the importance of telomeres to human health and aging, given that telomere damage can cause accelerated aging. Such findings pave the way towards the future possibility of slowing down the aging process, through the development of telomerase enhancing drugs. At the same time, while telomere damage already occurs in normal aging, increased damage has been associated with lifestyle choices such as smoking and obesity. Improving public awareness of lifestyle choices which may damage telomeres would thus contribute to managing the overall issue of aging as well e

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