Different types of cell death in organismal aging and longevity: state of the art and possible systems biology approach (original) (raw)

Programmed cell death in aging

Ageing research reviews, 2015

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, ...

Senescence, Apoptosis or Autophagy

Gerontology, 2008

briefly summarize the molecular networks that allow damaged cells either to adapt to stress or to engage in programmed-cell-death pathways.

Cellular longevity: Role of apoptosis and replicative senescence

Biogerontology, 2002

Cellular longevity refers to the lifespan of an individual cell. Normal cells have a finite lifespan and typically die by undergoing apoptosis, or enter into a state of irreversible growth arrest, termed replicative senescence, at the end of that lifespan. The lifespan of a cell is a balance between pro-survival/anti-apoptotic and pro-apoptotic deathpromoting factors. The role of heat shock proteins, Bcl-2 family members, antioxidant molecules, and telomere length and telomerase activity in the regulation of apoptosis and replicative senescence, will be discussed.

Apoptosis and successful aging

Mechanisms of Ageing and Development, 2002

Aging is inevitable, but successful aging, i.e. aging without chronic disease and/or decreased lifespan due to fatal disease, may be achievable. Our overall health relies to a great extent on the proper balance between the normal removal of damaged cell via apoptosis and proliferation of the cells that comprise our body. Tipping the delicate balance towards either side may cause diseases and hamper successful aging. Despite increasing interest in the relationship of apoptosis and aging in recent years, a role for apoptosis in aging remains obscure (reviewed in Zhang and Herman, 2002). Apoptosis plays a critical role in tissue homeostasis and is essential for normal development. The two well-documented apoptotic paradigms that have been defined over the past few years are the extrinsic and intrinsic pathways of apoptosis. The extrinsic pathway triggered by Fas ligand, signals through Fas receptor, Fas-associated protein with dead domain (FADD), the initiator caspase-8 and executioner caspases 3 and 7. The intrinsic pathway, mediated by mitochondria, signals through the apoptosome (a protein complex composed of cytochrome c, Apaf-1, and procaspase-9) and the executioner caspases 3, 6, and 7. Changes in either of these highly complex apoptotic-signaling net

Cellular lifespan and senescence: a complex balance between multiple cellular pathways

BioEssays, 2016

The study of cellular senescence and proliferative lifespan is becoming increasingly important because of the promises of autologous cell therapy, the need for model systems for tissue disease and the implication of senescent cell phenotypes in organismal disease states such as sarcopenia, diabetes and various cancers, among others. Here, we explain the concepts of proliferative cellular lifespan and cellular senescence, and we present factors that have been shown to mediate cellular lifespan positively or negatively. We review much recent literature and present potential molecular mechanisms by which lifespan mediation occurs, drawing from the fields of telomere biology, metabolism, NAD + and sirtuin biology, growth factor signaling and oxygen and antioxidants. We conclude that cellular lifespan and senescence are complex concepts that are governed by multiple independent and interdependent pathways, and that greater understanding of these pathways, their interactions and their convergence upon specific cellular phenotypes may lead to viable therapies for tissue regeneration and treatment of age-related pathologies, which are caused by or exacerbated by senescent cells in vivo.

Senescence in Post-Mitotic Cells: A Driver of Aging?

Antioxidants & Redox Signaling, 2020

Significance: Cell senescence was originally defined by an acute loss of replicative capacity and thus believed to be restricted to proliferation-competent cells. More recently, senescence has been recognized as a cellular stress and damage response encompassing multiple pathways or senescence domains, namely DNA damage response, cell cycle arrest, senescence-associated secretory phenotype, senescence-associated mitochondrial dysfunction, autophagy/mitophagy dysfunction, nutrient and stress signaling, and epigenetic reprogramming. Each of these domains is activated during senescence, and all appear to interact with each other. Cell senescence has been identified as an important driver of mammalian aging. Recent Advances: Activation of all these senescence domains has now also been observed in a wide range of post-mitotic cells, suggesting that senescence as a stress response can occur in nondividing cells temporally uncoupled from cell cycle arrest. Here, we review recent evidence for post-mitotic cell senescence and speculate about its possible relevance for mammalian aging. Critical Issues: Although a majority of senescence domains has been found to be activated in a range of postmitotic cells during aging, independent confirmation of these results is still lacking for most of them. Future Directions: To define whether post-mitotic senescence plays a significant role as a driver of aging phenotypes in tissues such as brain, muscle, heart, and others. Antioxid. Redox Signal. 34, 308-323.