Tubular Cell Senescence and Expression of TGF-β1 and p21WAF1/CIP1 in Tubulointerstitial Fibrosis of Aging Rats

Aging, tumor suppression and cancer: high wire-act!

“…Given that senescent cells secrete inflammatory cytokines, and that inflammation is thought to be an important contributory factor in atherogenesis, this result is consistent with the idea that senescent cells can initiate or promote age-related vascular disease. Similar types of evidence have implicated senescent cells in the etiology and/or progression of kidney fibrosis and age-related kidney dysfunction (Ding et al, 2001;Melk et al, 2003), osteoarthritis of the joints (Martin and Buckwalter, 2003) and venous ulcers of the lower extremities (Stanley and Osler, 2001).…”

“…Indeed, such (SABgal-positive) cells have been found in several tissues from humans and rodents. More important, their frequency has been shown to rise with increasing age in human skin, monkey skin and retina, human prostate, rodent kidney, human liver and human vascular endothelium (Dimri et al, 1995;Mishima et al, 1999;Pendergrass et al, 1999;Choi et al, 2000;Ding et al, 2001;Paradis et al, 2001;Vasile et al, 2001;Melk et al, 2003). Moreover, as discussed below, cells with senescent characteristics have been found at sites of age-related pathology, including atherosclerotic plaques and benign and premalignant lesions of the liver and prostate.…”

Cellular senescence and apoptosis: how cellular responses might influence aging phenotypes

“…Upon senescence, at least some cell types become resistant to certain apoptotic signals (Wang et al, 1994;Linskens et al, 1995;Seluanov et al, 2001). This resistance to apoptosis may explain why senescent cells can accumulate in tissues with age (Dimri et al, 1995;Pendergrass et al, 1999;Choi et al, 2000;Ding et al, 2001;Paradis et al, 2001). Equally important, senescent cells tend to overexpress secreted molecules, which can act at a distance within tissues and disrupt the local microenvironment.…”

“…As dysfunctional senescent cells accumulate in vivo (Dimri et al, 1995;Pendergrass et al, 1999;Choi et al, 2000;Ding et al, 2001;Paradis et al, 2001), their secretory phenotype might lead to disruption of the local tissue microenvironment. This disruption might explain the loss of tissue integrity and function that is a hallmark of aging (Campisi, 1997;Campisi, 2000).…”

Cellular senescence in the glaucomatous outflow pathway

“…Cellular senescence has been hypothesized to constitute an antagonistic pleiotropic response that protects against cancer early in life, but has cumulative deleterious effects, contributing to aging and certain age-related diseases (for a review on the pathological effects of senescent cells see Campisi, 2005). Consistent with this hypothesis, accumulation of cells expressing cellular senescence markers has been found to be associated with several pathologic conditions, such as atherosclerosis, kidney fibrosis, hepatic cirrhosis, and osteoarthritis (Johansson, 1984;Ding et al, 2001;Minamino et al, 2002;Wiemann et al, 2002;Martin and Buckwalter, 2003;Sasaki et al, 2005).…”