Cellular senescence is one of hallmarks of aging and accumulation of senescent cells with age contributes to tissue or organismal aging, as well as the pathophysiologies of diverse age-related diseases. Genetic ablation of senescent cells in tissues lengthened health span and reduced the risk of age-related pathologies in a mouse model, suggesting a direct link between senescent cells, longevity, and age-related diseases. Therefore, senotherapeutics, medicines targeting senescent cells, might be an emerging strategy for the extension of health span, and prevention or treatment of age-related diseases.
Senotherapeutics are classified as senolytics which kills senescent cells selectively; senomorphics which modulate functions and morphology of senescent cells to those of young cells, or delays the progression of young cells to senescent cells in tissues; and immune-system mediators of the clearance of senescent cells. Some senolytics and senomorphics have been proven to markedly prevent or treat age-related diseases in animal models.
This review will present the current status of the development of senotherapeutics, in relation to aging itself and age-related diseases. Finally, future directions and opportunities for senotherapeutics use will discussed. This knowledge will provide information that can be used to develop novel senotherapeutics for health span and age-related diseases.
During the last two decades, it has been well established that a short-term exposure to ozone (O3) elicits an oxidative stress response in human and mouse skin, which leads to aberrant transcriptional expression of genes consistent with increased skin aging. Whether a long-term exposure to ambient O3 is associated with any skin aging traits, has remained unclear.
We addressed this question in two elderly German cohorts: the SALIA study (806 women aged 66-79 years), and the BASE-II study (1207 men and women aged 60-84 years). Five-year mean residential exposure to O3 was modeled as the number of days with maximum daily 8-h mean O3 concentrations ≥120 μg/m3 per year in the wider neighborhood (5-digit postcode) of a participant’s residence. Extrinsic (environmentally induced) skin aging traits – coarse wrinkles and pigment spots (lentigines) on the face – were assessed by means of SCINEXA™, a validated visual score previously shown to be well suited to measure extrinsic facial skin aging in cohort studies.
We observed positive associations of O3 exceedances with coarse wrinkles in the face, but not with pigment spots. These associations were present in each cohort as well as in the combined sample of both cohorts. They were independent of chronic ultraviolet radiation exposure as the most obvious confounder, and also of co-pollutants such as particulate matter and nitrogen dioxide. Thus, long-term exposure to elevated concentrations of tropospheric ozone appears to contribute to skin aging.
Sirtuin is an essential factor that delays cellular senescence and extends the organismal lifespan through the regulation of diverse cellular processes. Suppression of cellular senescence by sirtuin is mainly mediated through delaying the age-related telomere attrition, sustaining genome integrity and promotion of DNA damage repair.
In addition, sirtuin modulates the organismal lifespan by interacting with several lifespan regulating signaling pathways including insulin/IGF-1 signaling pathway, AMP-activated protein kinase, and forkhead box O. Although still controversial, it is suggested that the prolongevity effect of sirtuin is dependent with the level of and with the tissue expression of sirtuin. Since sirtuin is also believed to mediate the prolongevity effect of calorie restriction, activators of sirtuin have attracted the attention of researchers to develop therapeutics for age-related diseases.
Resveratrol, a phytochemical rich in the skin of red grapes and wine, has been actively investigated to activate sirtuin activity with consequent beneficial effects on aging. This article reviews the evidences and controversies regarding the roles of sirtuin on cellular senescence and lifespan extension, and summarizes the activators of sirtuin including sirtuin-activating compounds and compounds that increase the cellular level of nicotinamide dinucleotide (NAD).
Acarbose improves health + lifespan (mice). Effect on weight, of acarbose (ACA) in dietary doses of 400-2500 ppm. Higher doses seem to correlate with weight stabilization. DATASOURCE:Aging Cell.WIDGET:factgraphs.org
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