Programmed cell death in aging

Abstract

Programmed cell death (PCD) pathways, including apoptosis and regulated necrosis, are required for normal cell turnover and tissue homeostasis. Mis-regulation of PCD is increasingly implicated in aging and aging-related disease. During aging the cell turnover rate declines for several highly-mitotic tissues. Aging-associated disruptions in systemic and inter-cell signaling combined with cell-autonomous damage and mitochondrial malfunction result in increased PCD in some cell types, and decreased PCD in other cell types. Increased PCD during aging is implicated in immune system decline, skeletal muscle wasting (sarcopenia), loss of cells in the heart, and neurodegenerative disease. In contrast, cancer cells and senescent cells are resistant to PCD, enabling them to increase in abundance during aging. PCD pathways limit life span in fungi, but whether PCD pathways normally limit adult metazoan life span is not yet clear. PCD is regulated by a balance of negative and positive factors, including the mitochondria, which are particularly subject to aging-associated malfunction.

Advanced oxidation protein products induce pre‐osteoblast apoptosis through a nicotinamide adenine dinucleotide phosphate oxidase‐dependent, mitogen‐activated protein kinases‐mediated intrinsic apoptosis pathway

“…MAPKs are redox sensitive and have also been shown to be involved in apoptosis in various cell types (Shen & Liu, 2006; Tower, 2015; Cagnol & Chambard, 2010). Therefore, we tested whether AOPPs activated MAPK signaling pathway.…”

“…Intrinsic apoptosis pathway is mainly characterized by mitochondria dysfunction and plays a role in the pathogenesis of age‐related disorders (Tower, 2015). Therefore, we examined whether AOPPs triggered intrinsic apoptosis pathway.…”

“…The intrinsic apoptosis pathway is a form of programed cell death which mainly characterized by mitochondria dysfunction (Shalini, Dorstyn, Dawar & Kumar, 2015; Tower, 2015). In this process, stimulation such as oxidative stress decreases the ▵Ψm, increases expression of BAX, and decreases Bcl‐2, and then results in mitochondrial membrane permeabilization and the releases of cytochrome c into cytoplasm, activates a series of pro‐apoptotic protein, and leads to cell death (Tower, 2015).…”

“…In this process, stimulation such as oxidative stress decreases the ▵Ψm, increases expression of BAX, and decreases Bcl‐2, and then results in mitochondrial membrane permeabilization and the releases of cytochrome c into cytoplasm, activates a series of pro‐apoptotic protein, and leads to cell death (Tower, 2015). In our study, AOPP stimulation significantly decreased ▵Ψm of osteoblastic cell and induced a marked expression of pro‐apoptosis protein such as cytochrome c, BAX, and cleaved caspase‐9, which activated the intrinsic pathway.…”

“…Apoptosis is thought to be one of the primary regulators of osteoblast homeostasis. Osteoblast apoptosis increases with age (Komori, 2016; Tower, 2015) and is responsible for reduction in osteoblast number and activity, which contribute to decreased bone formation (Jilka & O'Brien, 2016; Jilka, Weinstein, Parfitt & Manolagas, 2007; Weinstein & Manolagas, 2000). Therefore, increased osteoblast apoptosis results in the unbalanced coupling of bone formation and resorption and ultimately leads to bone loss and osteoporosis.…”