Damage to telomeres, mitochondrial and epigenetic dysfunction, and 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.
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 regards 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.
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.
