Link Between Cell Death, Cell Senescence and Neurodegenerative Disease

Link between cell death, cell senescence and neurodegenerative disease.

Bio 410: Cellular Senescence

Introduction

The definition of the term, ageing, holds different meanings for various scientists. Among the about 300 theories about ageing, some scientists believe that aging is a disease (Medvedev,1990). A commonly accepted definition is that ageing is an accumulation of changes that increase an organism’s probability of death or ageing consists of structural and chemical changes that result in progressive deterioration of bodily functions (Pedro de Magalhaes, 2004, Austad 1997). There are symptoms that are characteristic of this ageing phenotype and these include: loss of resistance to oxidative stress, accumulation of DNA damage (Medvedev, 1990), inefficiency of DNA repair mechanisms, shorter telomeres (Lukensa, 2009). The accumulation of DNA damage or short telomeres in a cell is sufficient to trigger the arrest of the cell from the cell cycle and reroute its fate to either a senescent or apoptotic one. The hallmarks of senescent cells are increase in cell volume, increase in senescent associated beta galactosidase (sa-βgal) activity (Nederi, 2006) and increase in p16 (Pedro de Magalhaes, 2004). The alternate fate, apoptosis or programmed cell death, is marked by increase in caspace activity and activation of PUMA (Thakur, 2009). Oxidative stress is a major culprit when it comes to inducing DNA damage (Chen & Ames, 1994). When there is an accumulation of reactive oxygen species (ROS) such as hydroxides, superoxides, either via internal cellular metabolism or external factors such as ultraviolet radiation, X-rays and chemicals, there is a correlating increase in DNA damage (Naderi, 2006).

Both senescent and apoptotic pathways are triggered by similar mechanisms. DNA damage or short telomere sequences activate the function of a critical tumor suppressor p53 (Efeyan, 2007). p53 is involved in cell surveillance and maintenance of chromosome integrity...