Transcriptome evidence reveals enhanced autophagy-lysosomal function in centenarians

Abstract

Centenarians (CENs) are excellent subjects to study the mechanisms of human longevity and healthy aging. Here, we analyzed the transcriptomes of 76 centenarians, 54 centenarian-children, and 41 spouses of centenarian-children by RNA sequencing and found that, among the significantly differentially expressed genes (SDEGs) exhibited by CENs, the autophagy-lysosomal pathway is significantly up-regulated. Overexpression of several genes from this pathway, CTSB, ATP6V0C, ATG4D, and WIPI1, could promote autophagy and delay senescence in cultured IMR-90 cells, while overexpression of the Drosophila homolog of WIPI1, Atg18a, extended the life span in transgenic flies. Interestingly, the enhanced autophagylysosomal activity could be partially passed on to their offspring, as manifested by their higher levels of both autophagyencoding genes and serum beclin 1 (BECN1). In light of the normal age-related decline of autophagy-lysosomal functions, these findings provide a compelling explanation for achieving longevity in, at least, female CENs, given the gender bias in our collected samples, and suggest that the enhanced waste-cleaning activity via autophagy may serve as a conserved mechanism to prolong the life span from Drosophila to humans.

Maximizing Longevity and Healthspan: Multiple Approaches All Converging on Autophagy

“…In support of this idea, healthy centenarians have been shown to have significantly higher levels of circulating beclin-1 compared to both young patients who have experienced an acute myocardial infarction and healthy young controls (Emanuele et al, 2014). This observation has been independently confirmed in a recent study that also showed a general increase in the expression of genes in the autophagy-lysosomal pathway in centenarians (Xiao et al, 2018).…”

History and progress of hypotheses and clinical trials for Alzheimer’s disease

“…368 On the other hand, transcriptome evidence has revealed enhanced autophagy-lysosome function in centenarians. 369 PPARA-mediated autophagy can reduce AD-like pathology and cognitive decline. 370 These results suggest that autophagy is a potential therapeutic target for AD.…”

Transcriptome profiling analysis of underlying regulation of growing follicle development in the chicken

“…With the development of genomic research, transcriptomics is one of the most widely used technologies ( Costa et al., 2010 ) that has been already used in studies of porcine growth ( Adapala and Kim, 2017 ), chicken skeletal muscle development ( Li et al., 2012b ), screening of sperm motility regulators ( Sun et al., 2019 ), human aging ( Xiao et al., 2018 ), poultry disease screening ( Matulova et al., 2012 ), and general genetic diversity ( Li et al., 2012a ). In poultry, most transcriptome studies focus on growth traits ( Allais et al., 2018 ) and meat quality ( Teng et al., 2019 ).…”