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“The Role of the Unfolded Protein Response in Mediating Adaptations to Exercise Responsiveness”
Author(s) -
Hart Corey R.,
Koh JinHo,
Dasari Surendra,
Lalia Antigoni Z.,
Lanza Ian R.
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.587.13
Subject(s) - unfolded protein response , atf6 , downregulation and upregulation , coactivator , skeletal muscle , endocrinology , biology , medicine , mitochondrion , endoplasmic reticulum , mitochondrial biogenesis , gene , microbiology and biotechnology , genetics , transcription factor
Aging is associated with altered mitochondrial physiology and exercise responsiveness in skeletal muscle. Activation of the unfolded protein response in the endoplasmic reticulum (UPR ER ) and mitochondria (UPR MT ) is linked with exercise‐induced adaptations in skeletal muscle, but the possibility that these processes impact exercise responsiveness and mitochondrial function in older humans has not been fully elucidated. The purpose of this study was to evaluate age‐related changes in UPR ER and UPR MT gene transcripts and protein abundance in response to a single bout of exercise. Muscle biopsies were obtained from 12 young (27±5 yr) and 12 older (75±5 yr) well‐matched, healthy men and women before exercise and 18h following a single bout of unilateral leg extension. Before exercise, a gene set enrichment analysis (GSEA) revealed that 27 genes associated with the UPR ER were upregulated in the older subjects compared to the young (enrichment false discovery rate [FDR] = 0.0842). After exercise, GSEA indicated upregulated UPR ER genes in both the young (FDR = 0.0405) and older subjects (FDR = 0.0619), however, pathway activation analysis revealed significantly greater activation of UPR ER and UPR MT gene transcripts post‐exercise in the younger subjects ( P < 0.05). In contrast, age did not affect key UPR‐regulatory protein abundance 18h post‐exercise. Interestingly, statistically significant correlations were observed in the young subjects between the mitochondrial transcriptional coactivator, peroxisome proliferator‐activated receptor gamma coactivator 1‐alpha (PGC‐1α) and key regulatory genes associated with the UPR ER (GRP78, R = 0.67; ATF6, R = 0.70) and the UPR MT (HSPE1, R = 0.61; HSPD1, R = 0.55; and HSPA9, R = 0.79), which were not evident in the older subjects. In conclusion, transcriptomic analysis revealed an age‐related decline in the adaptive UPR ER and UPR MT transcriptional response following a single bout of exercise that could potentially explain, in part, impaired exercise responsiveness and mitochondrial dysfunction with age. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .