Senescent cells accumulate throughout the body with advancing age. Somatic cells become senescent on reaching the Hayflick limit constantly throughout life, then quickly self-destruct or are destroyed by the immune system. As the immune system ages, however, it becomes less able to remove senescent cells in a timely fashion, and their numbers grow. Senescent cells are prolific generators of inflammatory signaling, and this activity is a major contribution to the chronic, unresolved inflammation that characterizes aged tissues. This inflammation is disruptive to tissue structure and function, changing cell behavior for the worse.
Many age-related diseases are characterized by inflammatory signaling and its detrimental effects. Periodontitis, inflammatory gum disease, can occur at any age given sufficient inattention to oral hygiene, but it is more prevalent in older people. One might expect this to be the case, given the increased inflammatory signaling present in an aged body. We might also ask whether the activities of senescent cells are involved in the pathology of gum disease, and in today's open access paper, researchers provide evidence to suggest that this is in fact the case.
Periodontitis is a chronic inflammatory disease characterized by periodontal tissue destruction with loss of tooth-supportive bone. It is thought to be the most common infectious disease and affects more than 40% of people aged over 30 years. Colonization of dental biofilm involving periodontopathic bacteria triggers inflammation and excessive immune responses that exacerbate breakdown of periodontal tissue. In addition to bactericidal pathogens, various environmental factors affect the pathology and progression of periodontal disease. In particular, aging has been recognized as a major risk factor that affects the onset and severity of periodontitis. Thus, understanding the biological mechanisms that regulate periodontal tissue and health by aging is an urgent issue to establish preventive protocols or specialized therapies for elderly persons in the field of periodontal medicine.
Cellular senescence is a major hallmark of senescence in organs and the whole body. Accumulated senescent cells in aged organs and tissues induce senescence of the body. A large number of studies have indicated that senescent cells secrete various proteins such as proinflammatory cytokines, chemokines, growth factors, and metalloproteinases, termed SASP (senescence-associated secretory phenotype). Therefore, understanding cellular senescence is required to develop more effective therapies and prevention protocols for age-dependent, lifestyle-related diseases. However, whether and how cell types within periodontal tissue undergo cellular senescence with SASP have not yet been clarified.
Recently, it has become evident that cellular senescence is a cause of chronic diseases through production of the SASP. In this study, we examined the pathological roles of cellular senescence in periodontitis. We found localization of senescent cells in periodontal tissue, particularly the periodontal ligament (PDL), in aged mice. Senescent human PDL (HPDL) cells showed irreversible cell cycle arrest and SASP-like phenotypes in vitro. Additionally, we observed age-dependent upregulation of miR-34a in HPDL cells. These results suggest that chronic periodontitis is mediated by senescent PDL cells that exacerbate inflammation and destruction of periodontal tissues through production of SASP proteins. Thus, miR-34a and senescent PDL cells might be promising therapeutic targets for periodontitis in elderly people.
View the full article at FightAging
