Autophagy Versus Progeria

Enhancing autophagy, the cellular housekeeping processes that recycle damaged components and proteins, is one of the possible approaches under investigation for treating a range of age-related conditions and modestly slowing aging. The accelerated aging condition progeria is caused by malformed lamin A, an important structural protein in cells. An accumulation of bad lamin A is something that also occurs in normal aging, albeit to a much lesser degree. Here, researchers propose turning autophagy to remove the damaged lamin A: "Farnesylated prelamin A is a processing intermediate produced in the lamin A maturation pathway. Accumulation of a truncated farnesylated prelamin A form, called progerin, is a hallmark of the severe premature ageing syndrome, Hutchinson-Gilford progeria. Progerin elicits toxic effects in cells, leading to chromatin damage and cellular senescence and ultimately causes skin and endothelial defects, bone resorption, lipodystrophy and accelerated ageing. Knowledge of the mechanism underlying prelamin A turnover is critical for the development of clinically effective protein inhibitors that can avoid accumulation to toxic levels without impairing lamin A/C expression, which is essential for normal biological functions. Little is known about specific molecules that may target farnesylated prelamin A to elicit protein degradation. Here, we report the discovery of rapamycin as a novel inhibitor of progerin, which dramatically and selectively decreases protein levels through a mechanism involving autophagic degradation. Rapamycin treatment of progeria cells lowers progerin, as well as wild-type prelamin A levels, and rescues the chromatin phenotype of cultured fibroblasts ... Importantly, rapamycin treatment does not affect lamin C protein levels ... Thus, rapamycin, an antibiotic belonging to the class of macrolides, previously found to increase longevity in mouse models, can serve as a therapeutic tool to eliminate progerin."

Link: http://www.ncbi.nlm.nih.gov/pubmed/22297442

Comments

I find this interesting, but not necessarily interesting enough to spend $18? downloading the full report which I will read once, understand half of, and then throw away. :) When they say 'dramatically' decreases protein levels, does that mean something closer to a 20% or 80% reduction.

Posted by: JohnD60 at February 6th, 2012 8:37 AM

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