With no known way around it, aging is the deterioration over time of an organism’s physiological functions necessary for survival, which eventually leads to death. Aging has what some believe to be three major hallmarks: primary drivers that cause damage; antagonistic drivers acting in response to the damage; and integrative drivers as a consequence of the damage which accrues over the lifetime of the cell.
Damage to telomeres, mitochondrial and epigenetic dysfunction, as well as damage to DNA are examples of primary drivers. Proteostasis dysfunctions and disruptions in signaling pathways are integrative drivers, while senescence is an antagonistic class driver.
What is senescence?
The technical versions
Senescence is the process of irreversible, stable growth arrest of cells which contributes to aging and age-related diseases. Senescence causes chromatin remodeling, increased autophagy, release of various complex proinflammatory factors, and changes in the phenotype of an organism. Senescence can occur in three ways: due to normal aging; due to age-related disease; and induced due to therapy such as chemotherapy.
There have been many studies conducted to understand senescence that happens due to the nature process of aging using two efficient animal models the senescence prone progeroid mouse models and transgenic mice. Studies on uninhibited by benzimidazole related 1 hypomorphic progeroid mice have revealed some types of cells are more susceptible to damage caused by senescence, such as fat and muscle progenitor cells are more vulnerable to senescence leading to loss of adipose tissue mass and sarcopenia.
Effects of cell automated senescence in stem cells leads to overall decline in tissue regenerative potential. Benzimidazole related 1 hypomorphic progeroid models showed senescence associated secretory phenotype affects the stem cells, resulting in structural changes to the extracellular matrix and interfering with the endocrine responsive signaling pathways.
Senescence typically sets in when the body is afflicted by a pathological condition. Some factors that drive senescence in age-related disease are loss of proliferation competent cells, SASP mediated inflammation, and remodeling of the extracellular matrix due to SASP. Senescence plays key roles in a variety of age-related disease such as diabetes, cancer, osteoarthritis, and glaucoma.
Tumor suppressors such as p16 INK4 and ARF induce senescence. Genome wide association studies have suggested a link between type 2 diabetes and senescence. Increased levels of markers and interleukin (IL)-1β were observed in β cells of diabetic model animals.
Articular chondrocytes undergo age related changes leading to decreased capacity to proliferate, causing loss of articular cartilage which is the hallmark of osteoarthritis.
Therapy induced senescence is observed while treating cases of pediatric blood cancer involving bone marrow transplantation and organ transplants. In regard to blood cancer chemotherapeutic intervention may promote senescence rich cells that impair the hematopoietic system and accelerate tissue deterioration, displaying as premature aging, cognitive impairment, and heart ailments.
The “general” version
Senescence refers to the process of aging and the gradual deterioration of functional characteristics in living organisms, which can be understood in two main contexts:
- Biological Aging: This involves the progressive decline in the ability of cells and tissues to function properly. Over time, this leads to increased vulnerability to diseases and a higher likelihood of death. Factors contributing to biological aging include genetic mutations, environmental damage, and the natural wear and tear of cellular processes.
- Cellular Senescence: This is the state where cells permanently stop dividing but do not die. (These undying cells have been called Zombie Cells due to the damage they cause to other cells and tissues around them.) Cellular senescence is also correlated with the shortening of telomeres. Cellular senescence be a protective mechanism against cancer, as it prevents damaged cells from proliferating. However, the accumulation of senescent cells can contribute to aging and age-related diseases.
Pharmacological and genetic tools can enhance understandings of mechanisms and relation between senescence and age-related decline in physiological functions, understandings will help to develop new therapeutic strategies to treat specific disease and improve overall health span of the aging population.
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- Mc Hugh D and Gil J. Senescence and aging: Causes, consequences, and therapeutic avenues. Journal of Cell Biology. 2017.
- Collado M, Blasco MA , and Serrano M. Cellular Senescence in Cancer and Aging. 2007 Jul;130(2);223-33.
- Childs BG, Durik M, Baker DJ et al. Cellular senescence in aging and age-related disease: from mechanisms to therapy. Nat Med. 2015 Dec;21(12):1424-35.
- Gilbert SF. Aging: The Biology of Senescence. Developmental biology. 2000. 6th
