Cellular aging

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Cellular aging also known as cellular senescence is a state where cells stop proliferating. Cell proliferation happens throughout an organism’s lifespan so newer cells replace older cells throughout the body. As such, cells undergoing senescence enter permanent “cell cycle arrest,” where they stop dividing and proliferating. The accumulation of these senescent cells can lead to tissues which cannot regenerate. Inflammation also occurs in such tissues, resulting in the progression of age-related diseases.[1][2][3] A main feature of aging is the build-up of cellular senescence.

Types of cellular senescence

Cellular senescence can occur due to different kinds of environmental stimuli, at least in cells and tissue in petri dishes in laboratories. Scientists still need to investigate whether these types of cellular senescence occur in living organisms. The two types of recognized cellular senescence is DNA damage-induced and Oxidative stress-induced senescence.

DNA damage-induced senescence

DNA damage-induced senescence constitutes one type of cellular senescence observed in laboratories. Depending on the magnitude of DNA damage, cell death can also occur in this situation. Scientists use radiation and drug-induced DNA damage to study this type of senescence. Oncogene-induced senescence occurs with activation of cancer-causing genes, oncogenes. This type of senescence can also occur with the activation of genes which suppress tumors, tumor suppressor genes.

Oxidative stress-induced senescence

Oxidative stress-induced senescence occurs with cellular production of byproducts of metabolism (metabolites), which cause cell stress through reactive oxygen species, unstable molecules or ions. Agents such as hydrogen peroxide can also induce this type of cellular senescence. Oxidative stress-induced senescence can cause DNA damage and also adversely affect other cellular components and processes. Chemotherapy-induced senescence results from multiple anticancer drugs used to induce senescence. Some anticancer drugs act through DNA damage, while others act through inhibition of cellular enzymes.

Induction of dysfunction in the cell’s powerhouse, mitochondrial dysfunction, also leads to senescence through mitochondrial dysfunction-associated senescence. This type of senescence typically occurs through the senescence-associated secretory phenotype (SASP), a set of inflammatory molecules which senescent cells secrete. Different cellular mechanisms lead to mitochondrial dysfunction, such as reduced integrity of the membrane or surface of the mitochondria. Dysfunctional generation of new mitochondria can also occur in cells, leading to reduced function of mitochondria.

Epigenetically-induced senescence occurs with the function of enzymes which alter gene activity. Some of these enzymes activate gene activity, histone demethylases, while others repress gene activity, histone deacetylases.

Cell characteristics to detect cellular senescence

Multiple characteristics have been used to determine whether cells are senescent. Combinations of these characteristics must be observed to determine senescence, because there is no single marker specifically indicating a cell has reached senescence. Therefore, scientists need to observe multiple cellular senescence characteristics to determine cellular senescence.

DNA damage response

Scientists can detect markers indicating repair of DNA damage. Phosphorylated p53, a signaling enzyme in the DNA damage response, can be used.[4] Cell cycle arrest: scientists measure the ability of cells to proliferate to determine whether they have undergone senescence. They also measure the rate of new DNA formation, DNA synthesis.

Cell secretion

What the cell secretes by measuring markers indicating inflammation, such as IL-6, can help determine if cells are senescent.[5]


This feature is not often used to determine senescence, because scientists cannot agree upon how senescence affects metabolism.

Cell size

Scientists can identify senescent cells based on their size using a microscope. Senescent cells have enlarged and irregular body shapes.[3]

Senescence and health

Senescent cells in adults accumulate in three conditions of human health: normal aging, diseases from aging, and therapeutic interventions.[6] In normal aging, dysfunctional tissue in the body occurs in all individuals. Diseases from aging only occur in some individuals. Dysfunctional tissue in older individuals causes damage, resulting in senescence.

Senescent cells accumulate in the body during the aging process due to immune system deficiencies. Senescent cells from repaired wounds, healed tumors, or other unknown processes may not undergo immune system disposal. This situation leads to aged, senescent cells which remain in the body. The tissues carrying aged, senescent cells become further susceptible to dysfunction when other stressors occur on the body.[6]

Additional stress to the body can result in disease with tissues carrying accumulations of aged, senescent cells. Tissue rich in aged, senescent cells are particularly vulnerable to disease when they contain aged fat coupled with a high-fat diet.[6][7][8][9] Stressors can come from unusual sources, such as cigarette smoke or erosion of the ends of chromosomes (telomeres) after repair from smoke-damaged lung tissue.[10][6]

Diseased tissue in the body also produces senescent cells. Accumulation of aged, senescent cells may occur in only one or a few organs. Accumulation of aged, senescent cells in these tissues occurs at a much higher rate due to prolonged and intense stressors from the disease.[6]

Therapy-induced accumulation of aged, senescent cells occurs as a response to potent stressors from outside of the body. This can occur as a side effect of medical treatments, due to the goal of the treatment, or due to both side effects and the goal. As an example, which encompasses both side effects and goals of treatment, DNA-damaging therapy and irradiation for cancer activates aging and senescence in tumor cells. The goal of the treatment is to eliminate cancer cells through causing them to age and senesce. As a side effect, healthy cells undergo aging and senescence as well.[6]


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