How does cellular senescence cause aging?

Since ancient times, the quest to stop aging has gripped many men and women. One proof of this search for the holy grail is the constant pursuit of the elixir of life, believed to bestow immortality and youthfulness in those who drink it. 

Despite the efforts devoted to this search for the fountain of youth, none has successfully stopped Father Time. However, scientists today have begun to unravel what causes aging. Although scientists admit that knowledge of the aging process is incomplete, they have started deciphering how cells undergo senescence, which precludes the aging process. 

What is cellular senescence? 

Senescence is a process in which cells in the body stop dividing and enter a growth arrest phase without dying. This process is irreversible and can be caused by cellular stress and unrepaired DNA damage [1].

Injury, stress factors, and disease harm different cells within the body. Ideally, when a cell is damaged, this is cleared by cells of the immune system. The cells undergo cell death or apoptosis.

However, during aging, removing dysfunctional cells is no longer effective. When this happens, this can contribute to less effective biological processes and a weakened immune system. 

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Cells that undergo senescence do not die or go through apoptosis. Since these cells do not die off when they should, they release chemicals that trigger inflammation. In turn, this action can damage neighbouring cells, spreading cellular senescence in tissues. 

However, some senescent cells are essential to the body. Senescent secretomes, the compounds and molecules expressed by senescent cells, have a crucial role across the lifespan, including wound healing, childbirth, and embryonic development [2]. 

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How does cellular senescence affect the body? 

Once an individual ages, the number of senescent cells also increases. Since the immune system of older adults is less efficient, clearing senescent cells as one age becomes more difficult.

The aging immune system can no longer cope with the volume of senescent cells that must be removed. This can affect an individual’s ability to recuperate from injuries, withstand illness or stress, and learn new things. It has been shown that senescent cells present in the brain can impair cognitive functions. 

Due to the impact of senescent cells on the body, these cells have been associated with conditions such as stroke, cancer, cardiovascular diseases, diabetes, and Alzheimer’s disease.

It is also related to osteoarthritis and other forms of dementia. There is also an association between senescent cells and poor eyesight and impaired executive functioning, such as decision-making and critical thinking. 

Further, senescent cells have also been linked to wrinkling and sagging. However, it is first necessary to examine the causes of aging to understand the link between senescent cells and aging. 

What are the causes of aging? 

Oxidative damage 

One of the suggested theories on aging involves oxidative damage. The mitochondria, which are the cell’s powerhouse, produce ATP to power metabolism and other cell processes.

Approximately 3% of the oxygen the mitochondria use for energy production is insufficiently reduced to ROS or reactive oxygen species [3]. Examples of ROS include hydrogen peroxide, the hydroxyl radical, and the superoxide ion.

These ROS can damage cell membranes, nucleic acids, and proteins. This can lead to aging as cells are disrupted with ROS. 

Mitochondrial damage 

The mutation rate in the cell’s powerhouse or the mitochondria is ten to twenty times faster than the mutation of the DNA found in the cellular nucleus.

It is believed that mitochondrial mutations could lead to increased production of reactive oxygen species (ROS), defects in energy production, and induce apoptosis. The mitochondrial function appears to decline with age in both animals and humans. 

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Telomere shortening 

Telomeres are described as repeated DNA sequences found at the ends of chromosomes. Unless maintained by telomerase, telomeres shorten with each cellular division.

Since most tissues of mammals lack telomerase, shortening of the telomere could act as a signal or a clock that the organism is aging. However, there is no correlation between telomere length and animal life span [3]. 

Genetic aging programs 

The combined effects of several genes have been shown to influence aging. For example, the condition called Hutchinson-Gilford progeria syndrome results in children aging rapidly and dying as early as twelve years old.

This condition is caused by mutation of a dominant sene with symptoms similar to aging such as arteriosclerosis, hair loss, resorbed bone mass, age spots and thinning of the skin. 

What are the factors that drive senescence? 

Damage of telomeres results in senescence in aging 

In adults, senescence is a response to different types of tissue damage. One of the factors that cause senescence includes damage to the chromosome’s telomeres.

When cells repeatedly divide and lack telomeres, this results in progressive erosion of the DNA, reduced binding to shelterin, the multicomplex protein that protects telomeres, and senescence. 

Metabolic dysfunction results in senescence 

Pathways that promote metabolic regulation have been shown to increase life span. However, during metabolic stress, there is increased inhibition of autophagy, which is the destruction of redundant or old cells. When autophagy is inhibited, senescent cells accumulate, resulting in aging. 

How do senescent cells cause aging? 

The presence of senescent cells can have detrimental or beneficial effects on the individual. Senescence has beneficial outcomes during embryonic development or early stages of the development of organisms.

Senescence allows the remodelling of tissues and the removal of unwanted cells as body tissues continue to develop [4]. In adults, it prevents the development of fibrotic tissue during wound healing.

Meanwhile, senescence is believed to be one of the reasons for age-related diseases and biological aging. How senescent cells cause aging is thought to be due to the following: 

  • Age aged immune system no longer efficiently eliminates senescent cells from tissues. 
  • Incompetent senescence-associated phenotype (SASP) that is released by senescent cells. 
  • It is believed that a combination of an aging immune system and incompetent SASP, along with other unknown factors, would lead to the accumulation of senescent cells and aging. 
  • The SASP are substances released by senescent cells. 

When the organism ages, the number of senescent cells also increases. When senescent cells continue to accumulate, this disrupts the functionality of the tissues, and second, senescence may limit the potential of adult stem cells to regenerate.

A combination of these mechanisms can then lead to aging. As previously mentioned, senescent cells secrete signals that activate immune system cells to remove them. However, during signalling, senescent cells are not only destroyed but also stem cells.

Further, during the repair of the tissues, tissue parts are not replaced with new cells but with fibrous tissues. 

Age-related diseases associated with the activation of senescence include the following: 

  •  Osteoarthritis 
  • Idiopathic pulmonary fibrosis 
  • Atherosclerosis 
  • Alzheimer’s disease 
  • Frailty 
  • Cancer 

In summary, senescent cells have been related to aging and other age-related diseases. Although research has been done to decipher how senescence causes aging, there is still no single treatment or intervention in preventing or delaying cell senescence.

More studies are still required to fully understand how to reverse aging by controlling the senescence of cells. 

Finally, oxidative stress must be reduced to delay cellular senescence. Currently, many good sources of antioxidants could help slow the aging process.

These include fruits and green and leafy vegetables, nuts, fish oil, berberine, turmeric, and berries. Drinking supplements that contain extracts of these food products could help delay aging. 

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