期刊
JOURNAL OF CELLULAR PHYSIOLOGY
卷 236, 期 7, 页码 5069-5079出版社
WILEY
DOI: 10.1002/jcp.30215
关键词
aging; cytosolic UPR; endoplasmic reticulum UPR; mitochondrial UPR; stress; temporal
资金
- National Institute on Aging [AG063766, AG028740]
- American Cancer Society [RSG-17-171-01-DMC]
- American Federation for Aging Research
- National Institutes of Health Office of Research Infrastructure Programs [P40 OD010440]
Proteotoxic stress is a common challenge for all organisms, and the evolutionarily conserved unfolded protein responses (UPRs) play a key role in defending such stress. Different subcellular compartments show distinct temporal regulation of UPRs during aging, with UPRs elevating with age but their inducibility declining. Different types of UPRs have varied temporal requirements for induction, and different tissues may exhibit distinct temporal profiles of UPR inducibility during aging.
Proteotoxic stress is a common challenge for all organisms. Among various mechanisms involved in defending such stress, the evolutionarily conserved unfolded protein responses (UPRs) play a key role across species. Interestingly, UPRs can occur in different subcellular compartments including the endoplasmic reticulum (UPRER), mitochondria (UPRMITO), and cytoplasm (UPRCYTO) through distinct mechanisms. While previous studies have shown that the UPRs are intuitively linked to organismal aging, a systematic assay on the temporal regulation of different type of UPRs during aging is still lacking. Here, using Caenorhabditis elegans (C. elegans) as the model system, we found that the endogenous UPRs (UPRER, UPRMITO, and UPRCYTO) elevate with age, but their inducibility exhibits an age-dependent decline. Moreover, we revealed that the temporal requirements to induce different types of UPRs are distinct. Namely, while the UPRMITO can only be induced during the larval stage, the UPRER can be induced until early adulthood and the inducibility of UPRCYTO is well maintained until mid-late stage of life. Furthermore, we showed that different tissues may exhibit distinct temporal profiles of UPR inducibility during aging. Collectively, our findings demonstrate that UPRs of different subcellular compartments may have distinct temporal mechanisms during aging.
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