Senescence
Nate F. Cardarelli in The Thymus in Health and Senescence, 2019
This chapter provides a brief overview of the historical context, lifespan studies, symptomatology of senescence, and the pros and cons of the more popular "theories". The free radical "theory" is promising because of its ability to explain the beneficial effects of food restriction, the clustering of terminal diseases in the latter part of life, increases in autoimmunity with age, and a correlation of lifespan with metabolic rate. Most of the hominid increase in brain size occurred in the last 2 million years, as well as most of man’s lifespan increase. The great I. I. Metchnikov, theorizing about senescence, maintained that the same cellular mechanism that controlled morphogenesis in the embryo, also defended the cell from pathogenic and environmental challenge. R. W. Hart and R. B. Setlow suggested that aging is an error in replication or repair of deoxyribonucleic acid since there is a correlation between mammalian species lifespan and efficacy of excision repair at the chromosome level.
Cellular Aging
Roger B. McDonald in Biology of Aging, 2019
This chapter begins with a brief review of essential concepts in general cell biology that pertain to the aging of cells. It describes the cause of aging and how that manifests in cells. The chapter explores a possible aging mechanism underlying cellular aging that leads to a decline in function and determines the life span of the entire organism. It looks at how the most basic function of a cell, energy metabolism, can produce by-products having the potential to cause damage. The chapter discusses how development of time-dependent pathologies, such as cancer, reflects a loss in molecular fidelity within a highly conserved pathway selected to protect the tissue and impart a reproductive advantage. It also explores the relationship between cell senescence and telomeres, the repetitive, noncoding base-pair sequences at the ends of each chromosome. The chapter explains how the loss of telomeres occurring during each round of the cell cycle can trigger biochemical pathways that lead to permanent growth arrest.
Introduction
Constantin A. Bona, Francisco A. Bonilla in Textbook of Immunology, 2019
Most of us are aware that our bodies contain something called an “immune system” which protects us from infectious microbes. The notion of immunity as protection from harmful organisms is the most prominent feature of the current immunological paradigm. We have learned recently, however, that the immune system has other roles than that of a “guardian” at points of entry to the body. The immune system acts to destroy our own cells that develop aberrantly (cancers) as well as to eliminate dead or senescent cells and defunct proteins from the blood and other tissues. The intimate interconnections of immune and neuroendocrine systems is coming to light, and we have also recently discovered that defects or dysregulation of the immune system may result in a tremendous variety of pathologies. Since the immune system interacts with every other system of the body, a knowledge of its physiology and pathology is important in every medical specialty.
Type 1 interferons contribute to the clearance of senescent cell
Published in Cancer Biology & Therapy, 2015
Yuliya V Katlinskaya, Christopher J Carbone, Qiujing Yu, Serge Y Fuchs
The major known function of cytokines that belong to type I interferons (IFN, including IFNα and IFNβ) is to mount the defense against viruses. This function also protects the genetic information of host cells from alterations in the genome elicited by some of these viruses. Furthermore, recent studies demonstrated that IFN also restrict proliferation of damaged cells by inducing cell senescence. Here we investigated the subsequent role of IFN in elimination of the senescent cells. Our studies demonstrate that endogenous IFN produced by already senescent cells contribute to increased expression of the natural killer (NK) receptor ligands, including MIC-A and ULBP2. Furthermore, neutralization of endogenous IFN or genetic ablation of its receptor chain IFNAR1 compromises the recognition of senescent cells and their clearance in vitro and in vivo. We discuss the role of IFN in protecting the multi-cellular host from accumulation of damaged senescent cells and potential significance of this mechanism in human cancers.
Erythrocyte senescence and membrane transporters in young and old rats
Published in Archives of Physiology and Biochemistry, 2016
Sandeep Singh, Kanti Bhooshan Pandey, Syed Ibrahim Rizvi
Alterations at the level of plasma membrane are reported to play an important role in cellular senescence. The present study was undertaken to correlate cellular senescence, membrane transport processes and organismal aging. To achieve this objective activities of membrane linked Na+/K + ATPase (NKA), Na+/H+ exchanger (NHE) and correlation with membrane hydrxyperoxide level, sialic acid content and membrane protein oxidation was studied in density-gradient fractionated young and old erythrocytes from 4 and 24 month old Wistar rats. The results reveal that cellular aging within the tissue is associated with significant decrease in activities of NKA and NHE of senescent erythrocytes in comparison to younger cell population of same age group. The result shows that impaired ion homeostasis due to altered membrane transporters including functional and compositional changes may be one of the reasons responsible behind rat erythrocyte aging.
The emerging role of senescent cells in tissue homeostasis and pathophysiology
Published in Pathobiology of Aging & Age-related Diseases, 2015
Cellular senescence is a state of permanent growth arrest and is thought to play a pivotal role in tumor suppression. Cellular senescence may play an important role in tumor suppression, wound healing, and protection against tissue fibrosis in physiological conditions in vivo. However, accumulating evidence that senescent cells may have harmful effects in vivo and may contribute to tissue remodeling, organismal aging, and many age-related diseases also exists. Cellular senescence can be induced by various intrinsic and extrinsic factors. Both p53/p21 and p16/RB pathways are important for irreversible growth arrest in senescent cells. Senescent cells secret numerous biologically active factors. This specific secretion phenotype by senescent cells may largely contribute to physiological and pathological consequences in organisms. Here I review the molecular basis of cell cycle arrest and the specific secretion phenotype in cellular senescence. I also summarize the current knowledge of the role of cellular senescence in vivo in physiological and pathological settings.
Related Knowledge Centers
- Cell Death
- DNA Damage
- Oxidative Stress
- Metabolism
- Immune System
- Growth & Development
- Ungrateful Dead