Effects of environmental determinants for cell aging and its consequences for the healthy or pathological aging

Abstract

Life expectancy has been increasing year by year, and ages that have not been reached have become common in Brazil and worldwide. The aging process is associated with cellular changes that influence the function of tissues and organs. An important mechanism related to this process and which appears to be a factor related to many diseases linked to age is cellular aging. It is believed that the deleterious effects of cell aging are related to its ability to stop its development and acquire a secretory phenotype known as senescence-associated secretory phenotype (SASP) producing factors such as inflammatory cytokines, chemokines, proteases and growth factors capable of damaging neighboring tissues. Thus, a tissue environment conducive to the development of chronic inflammation, cancers and neurodegenerative processes is established. In a recent work of our research team, supported by FAPESP (processes 2018/05288-6 and 2020/07701-8), it was verified that human astrocytes derived from induced pluripotent stem cells (iPSCs) showed significant markings for SASP that were reduced with the incubation of low concentrations of lithium carbonate (2.5 µM and 10 µM), which has become a research perspective for new treatments of COVID-19. This proposal aims to collect behavioral and biological information from elderly people diagnosed or not with Alzheimer's disease or belonging to the group risk for COVID-19 (hypertensive, diabetic or with respiratory problems), in addition to individuals from other age groups. From the collection of gums samples, fibroblasts will be cultured. The fibroblast is a well-studied cell type that expresses SASP and is a cell model of Alzheimer's disease. The goal is to stratify the susceptibility of fibroblasts to aging concerning age, lifestyle and stressors. Then, it is intended to determine whether these effects can be reduced or eliminated with treatment with possible senolytics (drugs that eliminate cell aging). The data obtained may serve as a basis for individualized treatments, with greater therapeutic success and fewer adverse effects. (AU)