Macroautophagy is impaired in old murine brain tissue as well as in senescent human fibroblasts

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• 作者：Christiane Ott^a ; ^{Christiane.Ott@dife.de" class="auth_mail" title="E-mail the corresponding author} ; Jeannette Kö ; nig^a ; ^{Jeannette.Koenig@dife.de" class="auth_mail" title="E-mail the corresponding author} ; Annika Hö ; hn^a ; ^b ; ^{Annika.Hoehn@dife.de" class="auth_mail" title="E-mail the corresponding author} ; Tobias Jung^a ; ^c ; ^{Tobias.Jung@dife.de" class="auth_mail" title="E-mail the corresponding author} ; Tilman Grune^a ; ^b ; ^c ; ^{scientific.director@dife.de" class="auth_mail" title="E-mail the corresponding author}
• 关键词：ConA ; Concanamycin A (lysosomal inhibitor) ; LC3 ; Microtubule-associated protein 1A/1B-light chain 3 ; mTOR ; mammalian target of rapamycin ; ATGs ; Autophagy-related proteins ; ALP ; Autophagy-Lysosome pathway ; MA ; Macroautophagy
• 刊名：Redox Biology
• 出版年：2016
• 出版时间：December 2016
• 年：2016
• 卷：10
• 期：Complete
• 页码：266-273
• 全文大小：1455 K

文摘

The overall decrease in proteolytic activity in aging can promote and accelerate protein accumulation and metabolic disturbances. To specifically analyze changes in macroautophagy (MA) we quantified different autophagy-related proteins (ATGs) in young, adult and old murine tissue as well as in young and senescent human fibroblasts. Thus, we revealed significantly reduced levels of ATG5-ATG12, LC3-II/LC3-I ratio, Beclin-1 and p62 in old brain tissue and senescent human fibroblasts. To investigate the role of mTOR, the protein itself and its target proteins p70S6 kinase and 4E-BP1 were quantified. Significant increased mTOR protein levels were determined in old tissue and cells. Determination of phosphorylated and basal amount of both proteins suggested higher mTOR activity in old murine tissue and senescent human fibroblasts. Besides the reduced levels of ATGs, mTOR can additionally reduce MA, promoting further acceleration of protein accumulation and metabolic disturbances during aging.