Genes related to maintenance of autophagy and successful aging.

Carolina Fioroto Chaves,Maysa Seabra Cendoroglo,Luiz Roberto Ramos,Vanessa Cavalcante Da Silva,Diego Robles Mazzotti,Vânia D'Almeida,Sergio Tufik

doi:10.1590/0004-282x20180142

Carolina Fioroto Chaves, Maysa Seabra Cendoroglo + Show 5 more

Open Access

https://doi.org/10.1590/0004-282x20180142

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Abstract

Considering aging as a phenomenon in which there is a decline in essential processes for cell survival, we investigated the autophagic and proteasome pathways in three different groups: young, older and oldest old male adults. The expression profile of autophagic pathway-related genes was carried out in peripheral blood, and the proteasome quantification was performed in plasma. No significant changes were found in plasma proteasome concentrations or in correlations between proteasome concentrations and ages. However, some autophagy- and/or apoptosis-related genes were differentially expressed. In addition, the network and enrichment analysis showed an interaction between four of the five differentially expressed genes and an association of these genes with the transcriptional process. Considering that the oldest old individuals maintained both the expression of genes linked to the autophagic machinery, and the proteasome levels, when compared with the older group, we concluded that these factors could be considered crucial for successful aging.

Highlights

Considering aging as a phenomenon in which there is a decline in essential processes for cell survival, we investigated the autophagic and proteasome pathways in three different groups: young, older and oldest old male adults
Studies in C. elegans and D. melanogaster have shown that the loss of function of autophagy genes is related to an accumulation of damaged organelles and proteins, accelerated aging and shortened life span[23,24,25]
To evaluate the contribution of the autophagic machinery in successful aging, we quantified the expression of 84 genes related to the autophagic pathway in young, older and oldest old individuals; five presented with differential expression between the studied groups: ATG4C, BCL2L1, TP53, EIF2AK3 and EIF4G1

Summary

Introduction

Considering aging as a phenomenon in which there is a decline in essential processes for cell survival, we investigated the autophagic and proteasome pathways in three different groups: young, older and oldest old male adults. The ubiquitin-proteasome is a multicatalytic ATPdependent degradation system found in both cytoplasm and cell nucleus[3,4,5] This system is related to the degradation of normal or abnormal proteins, and some studies have shown decreased proteasomic activity during aging in different human tissues such as muscle and epidermis[6,7,8]. A study developed by Lee et al.[9] showed a reversion in decreased proteasome gene expression in the skeletal muscle of mice submitted to caloric restriction, indicating that this intervention may contribute to the prevention of aging by increasing degradation of damaged proteins. The origin of these circulating proteasomes is still unknown, some studies have reported their increased concentrations in pathological conditions such as cancer[13,14], and suggested a correlation between proteasome concentrations and health status[10,15,16]

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