A comparative analysis of the cell biology of senescence and aging

Abstract

Various intracellular organelles, such as lysosomes, mitochondria, nuclei, and cytoskeletons, change during replicative senescence, but the utility of these changes as general markers of senescence and their significance with respect to functional alterations have not been comprehensively reviewed. Furthermore, the relevance of these alterations to cellular and functional changes in aging animals is poorly understood. In this paper, we review the studies that report these senescence-associated changes in various aging cells and their underlying mechanisms. Changes associated with lysosomes and mitochondria are found not only in cells undergoing replicative or induced senescence but also in postmitotic cells isolated from aged organisms. In contrast, other changes occur mainly in cells undergoing in vitro senescence. Comparison of age-related changes and their underlying mechanisms in in vitro senescent cells and aged postmitotic cells would reveal the relevance of replicative senescence to the physiological processes occurring in postmitotic cells as individuals age.

Senescence Effects of Angelica sinensis Polysaccharides on Human Acute Myelogenous Leukemia Stem and Progenitor Cells

“…In addition to losing the ability to divide, cells in the senescent state exhibit dramatic alterations in morphology, mass, and dynamics of their sub-cellular organelles, and thereby display structural and functional differences compared to proliferating cells. These differences include an enlarged and flat cellular morphology, mitochondria aggregation and swell , lipofuscins and granular particles, altered mass and functionality of mitochondria and lysosomes, and certain cytosolic and nuclear markers such as senescenceassociated heterochromatin foci (SAHF) (Hwang et al, 2009), in common with results of ultra structure analysis in current work.…”

“…ASP had a minor effect on positive rate in normal CD34 + CD38 − cells (Figure 3a, b). In addition to losing the ability to divide, cells in senescent state exhibit dramatic alterations in morphology and dynamics of their subcellular organelles, such as enlarged and flat cellular morphology, mitochondria aggregation and swell, edema of Golgi complex, formation of nuclear marker senescence-associated heterochromatin foci (SAHF) (Narita ., 2003;Hwang et al, 2009). These ultra structure changes on AML CD34 + CD38 − cells after ASP treatment have been observed under transmission electron microscope in current work (Figure 3c).…”

Nicotinamide-induced Mitophagy

“…Mitophagy coupled with this structural dynamic functions in removing the depolarized parts of mitochondria. Mitochondrial dynamics appear to be implicated in many cellular processes, including proliferation, apoptosis (50), and senescence (51). For example, fission activity declines during the course of cellular senescence (10), and conversely, blocking mitochondrial fission leads to senescence (11).…”

Kinetics of the Cell Biological Changes Occurring in the Progression of DNA Damage-Induced Senescence

“…Short and unprotected telomeres resulting from prolonged DNA replication trigger a continuous DNA damage response, which leads to permanent arrest of the cell cycle (Campisi et al, 2001). Senescence results in specific cell biological changes, which include enlargement and flattening of the cytoplasm, increased production of reactive oxygen species (ROS), accumulation of lipofuscins, increased mitochondrial and lysosomal mass and their cellular contents, and loss of mitochondrial membrane potential (MMP) (Hwang et al, 2009). Senescent cells also express cytosolic and nuclear markers such as senescence-associated β-galactosidase (SA β-Gal) activity (Dimri et al, 1995) and senescence-associated heterochromatin foci (SAHF) (Nakata et al, 2006).…”