Apoptosis in the aging process

Abstract

Although many hypotheses have been proposed to explain the aging process, the exact mechanisms are not well defined. Recent accumulating evidence indicates that dysregulation of the apoptotic process may be involved in some aging processes; however, it is still debatable how exactly apoptosis is expressed during aging in vivo. In this review, we discuss recent findings related to apoptosis of individual organs during aging and their significance. We demonstrate that aging enhances apoptosis and susceptibility to apoptosis in several types of intact cells. In contrast, in certain genetically damaged, initiated, and preneoplastic cells, aging suppresses these age-associated apoptotic changes. In various cells, apoptosis enhances the elimination of damaged and dysfunctional cells presumably caused by oxidative stress, glycation, and DNA damage. In these cases, the incidence of apoptosis correlates with the level of accumulated injury. It is concluded that apoptosis plays an important role in the aging process and tumorigenesis in vivo probably as an inherent protective mechanism against age-associated tumorigenesis.

Survivin expression increases during aging and enhances the resistance of aged human fibroblasts to genotoxic stress

“…This is in agreement with other studies that have reported a decrease in induced apoptosis in old cells in response to different stimuli, including oxidative stress (Higami and Shimokawa 2000;Lee and Wei 2007) and γ-rays (Polyak et al 1997). Likewise, previous studies have shown that senescent fibroblasts are resistant to apoptosis induced by UV light (Ryu et al 2006) oxygen radicals (Gansauge et al 1997), serum withdrawal, H 2 O 2 , staurosporine, and thapsigargin (Wang 1995;Ryu et al 2006Ryu et al , 2007.…”

“…Likewise, previous studies have shown that senescent fibroblasts are resistant to apoptosis induced by UV light (Ryu et al 2006) oxygen radicals (Gansauge et al 1997), serum withdrawal, H 2 O 2 , staurosporine, and thapsigargin (Wang 1995;Ryu et al 2006Ryu et al , 2007. On the other hand, other studies have shown that aging enhances apoptosis triggered by various challenges (Higami and Shimokawa 2000;Lee and Wei 2007). Indeed, fibroblasts cultured from old individuals were more sensitive to H 2 O 2 -induced apoptosis than those cultured from younger ones (Miyoshi et al 2006).…”

“…Apoptosis also increased with age in cells of AL-fed mice incubated with H 2 O 2 (Avula and Fernandes 2002). These discrepancies are probably due to the use of different species, different strains, or different cell types (Higami and Shimokawa 2000). It is also possible that these differences result from the differences between mitotic and post-mitotic tissues, as aging of post-mitotic tissues is known to be associated with a general enhancement of apoptosis, and this trend seems to be essential for the removal of damaged and dysfunctional non-replaceable cells (Higami and Shimokawa 2000;Campisi 2003).…”

Rorα, a pivotal nuclear receptor for Purkinje neuron survival and differentiation: From development to ageing

“…Whereas half-dose of functional RORα protein seems to be sufficient to allow Purkinje cell survival during development, Rora +/sg mutant PCs are not protected against age-associated injuries. Among these, an increased vulnerability to oxidative stress is thought to play a critical role in age-related cell death (reviewed in (48)(49)(50). To test whether an increased RORα expression could be neuroprotective, we have recently developed a recombinant lentiviral vector to perform RORα overexpression in cultured neurons.…”

Advanced Glycation End Products Enhance Expression of Pro-apoptotic Genes and Stimulate Fibroblast Apoptosis through Cytoplasmic and Mitochondrial Pathways

“…Interestingly, enhanced apoptosis of these cells is also associated with diabetic complications such as retinopathy, neuropathy, nephropathy, and accelerated vasculopathy (38 -40). Enhanced apoptosis has been linked to many of the detrimental effects of aging, which is also associated with AGE accumulation (41). Because fibroblasts play important roles in the maintenance and healing of dermal connective tissue, the accumulation of AGEs in skin may have a detrimental effect, in part, through promoting fibroblast apoptosis.…”