New Data on Progerin and Cellular Senescence in Normal Aging

In this study, we used a mouse model with sustained long-term expression of human progerin in a low frequency of cells of the adipose tissue to determine the contribution of progerin to progressive sWAT depletion. Our results provide evidence that adipose tissue is highly sensitive to progerin expression and further emphasize progerin's possible causal role in certain tissue alterations during aging. However, the frequency of progerin positive cells in the sWAT of our mouse model was higher than what was observed in healthy human sWAT, in which progerin could not be detected on protein level. Other researchers have suggested a hypothetical model whereby aging of adipose tissue results in cellular senescence and consequent tissue pathology. Our results provide evidence that a similar mechanism is to be found in subcutaneous fat, with progerin accumulation during aging triggering a cascade of events contributing to progressive tissue depletion. We propose that with chronic exposure to low numbers of progerin expressing cells, sWAT pathology begins, initially with hyperproliferation. Hyperproliferation in turn contributes to abnormal cellular development and subsequent senescence. As paracrine activity is high in adipose tissue, senescence spreads to surrounding cells through activation of the senescence-associated secretory phenotype (SASP). Simultaneously, aging sWAT accumulates DNA double-strand breaks, which upon reaching a certain threshold lead to an increase in cel...
Source: Fight Aging! - Category: Research Authors: Tags: Medicine, Biotech, Research Source Type: blogs