Major Theories of Aging and Cellular Changes During Aging

  • Cellular ageing is described as a gradual loss of cellular functioning and eventual cell death caused by a cumulative fall in resistance to stress and other cellular damages. Replicative ageing, Replicative ageing, which refers to the limited number of divisions that a single cell can attain. Chronological ageing, Chronological ageing, which is measured in time units by determining the mean and the maximum survival time of a post-mitotic yeast population and not of single cells.

List the major theories of aging

  • We are all familiar with the outward signs of aging, such as wrinkled skin, gray hair, and reduced vision. A number of cellular structures or events appear to be involved in causing these effects. The major hypotheses that attempt to explain how aging occurs concentrate on molecules within the cell, such as lipids, proteins, and nucleic acids. It is estimated that at least 35% of the factors affecting aging are genetic.
  • Cellular clock: One hypothesis of aging suggests the existence of a cellular clock that, after a certain passage of time or a certain number of cell divisions, results in the death of a given cell line. Cellular clock theory of aging focuses on the lifespan of cells. Since many human cells do not continue to reproduce indefinitely, this theory suggests that aging is a result of cells hitting their programmed reproductive limit.
  • Death genes: Another hypothesis suggests that there are “death genes,” which turn on late in life, or sometimes prematurely, causing cells to deteriorate and die. Genes that promote ageing include some that encode yolk proteins, consistent with a link between ageing and reproduction. Another pro-ageing protein is the insulin-like INS-7, which, by binding to the insulin/IGF-1 receptor (DAF-2), may repress DAF-16 on the same and other cells.
  • DNA damage: Other hypotheses suggest that, through time, Deoxyribonucleic acid (DNA) is damaged, resulting in cell degeneration and death. DNA damage contributes to aging via cell autonomous events such as causing apoptosis, which depletes functional cells such as neurons, and via cell non-autonomous mechanisms such as triggering senescence, which can negatively impact the function of neighboring, undamaged cells through their SASP
  • Free radicals: DNA is also susceptible to direct damage, resulting in mutations that may result in cellular dysfunction and, ultimately, cell death. One of the major sources of DNA damage is apparently free radicals, which are atoms or molecules with an unpaired electron.
  • Mitochondrial damage: Mitochondrial DNA may be more sensitive to free-radical damage than is nuclear DNA. Mitochondrial DNA damage may result in loss of proteins critical to mitochondrial function. Because the mitochondria are the primary source of ATP, loss of mitochondrial function could lead to the loss of energy critical to cell function and, ultimately, to cell death. One proposal suggests that reduced caloric intake may reduce free-radical damage to mitochondria.

Cellular Changes during Aging

  • With age, all cells undergo modifications. They grow in size and lose their ability to divide and replicate. Inside the cell, there is a rise in pigments and fatty compounds, among other modifications (lipids). Many cells lose their ability to operate, or their functions become aberrant.
  • As the cell ages the plasma membrane has increases amount fatty acids. This structural change decreases the fluidity of the plasma membrane and reduces the transportation of ions, nutrients, amino acids, and proteins across the membrane.
  • As the cell ages cross-linkages form between the sulfur atoms on the DNA in the nucleus of the cells. This structural change condenses the DNA which decreases the synthesis of RNA, reduced the cells ability to repair enzymes, and may reduce the cell’s ability to divide.
  • As the cell ages the volume of cytoplasm increases, enzymes that synthesize DNA move from the nucleus to the cytoplasm, and there is a gradual build-up of lipofuscin. While it is unclear how this directly affects the cell, it is known that once the DNA migrates from the nucleus it is unable to synthesizes enzymes.
  • Aging is associated with a gradual decline of organismal function and fitness, which in turn is tightly linked with changes in the proteome. The balance between protein synthesis and degradation, proteostasis, and proper protein quality control is required to maintain cell homeostasis
  • Age-related changes in mitochondria are associated with decline in mitochondrial function. With advanced age, mitochondrial DNA volume, integrity and functionality decrease due to accumulation of mutations and oxidative damage induced by reactive oxygen species (ROS)..
  • As the cell ages the lysosomes become less able to break down waste proteins, nucleic acids, carbohydrates, and fats. This result is a build-up waste within the cell. Lysosomes figure prominently in theories of aging as the proteolytic system most responsible for eliminating growing burdens of damaged proteins and organelles in aging neurons and other long lived cells

Further Readings