A Specific Example of Harm Caused By Senescent Cells

Here's a detailed look at one narrow form of dysfunction caused by the accumulation of senescent cells in tissue. Senescent cells gather with age in all tissues, and similar processes are thought to take place throughout the body - which is why targeted removal of senescent cells is an important part of any future toolkit for rejuvenation:

Renal aging is associated with an increased susceptibility to acute stress and tubular cell injury. While the young kidney has a remarkable capacity to recover from acute injury, the aging kidney loses this repair reserve and instead develops an increasing tendency for tubular atrophy and interstitial fibrosis. Our previous data suggest that a loss in tubular epithelial proliferative reserve contributes importantly to inappropriate repair in the aged kidney.

Under baseline conditions the renal tubular epithelium has a low rate of cellular turnover when compared to other tissues. In mouse kidney less than 1% of proximal tubular cells express proliferation markers under normal conditions. In response to acute damage, however, the renal epithelium can initiate a burst of proliferation which serves to repopulate and restore injured tubules. This injury-response may lead to full functional recovery even after extensive tubule denudation.

We have previously shown that the proliferative potential of tubular cells declines with chronological age. In previous studies we linked the inability to increase cell cycling to somatic cellular senescence (SCS) by demonstrating that genetic induction of telomere shortening, as a model of telomere dependent SCS in mice, was associated with a decline in the tubular proliferative capacity. Ablation of the pro-senescent p16INK4A, on the other hand, resulted in improved regeneration and better proliferation following acute ischemic renal injury.

Link: http://dx.doi.org/10.1371/journal.pone.0088071


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