Changes in macroautophagy, chaperone-mediated autophagy, and mitochondrial metabolism in murine skeletal and cardiac muscle during aging
Aging causes a general decline in cellular metabolic activity, and function in different tissues and whole body homeostasis. However, the understanding about the metabolomic and autophagy changes in skeletal muscle and heart during aging is still limited. We thus examined markers for macroautophagy,...
| Main Authors: | , , , , , , |
|---|---|
| Other Authors: | |
| Format: | Journal Article |
| Language: | English |
| Published: |
2018
|
| Subjects: | |
| Online Access: | https://hdl.handle.net/10356/102485 http://hdl.handle.net/10220/47261 |
| _version_ | 1826110908351381504 |
|---|---|
| author | Zhou, Jin Chong, Shu Yun Lim, Andrea Singh, Brijesh K. Sinha, Rohit A. Salmon, Adam B. Yen, Paul M. |
| author2 | School of Biological Sciences |
| author_facet | School of Biological Sciences Zhou, Jin Chong, Shu Yun Lim, Andrea Singh, Brijesh K. Sinha, Rohit A. Salmon, Adam B. Yen, Paul M. |
| author_sort | Zhou, Jin |
| collection | NTU |
| description | Aging causes a general decline in cellular metabolic activity, and function in different tissues and whole body homeostasis. However, the understanding about the metabolomic and autophagy changes in skeletal muscle and heart during aging is still limited. We thus examined markers for macroautophagy, chaperone-mediated autophagy (CMA), mitochondrial quality control, as well as cellular metabolites in skeletal and cardiac muscle from young (5 months old) and aged (27 months old) mice. We found decreased autophagic degradation of p62 and increased ubiquitinated proteins in both tissues from aged mice, suggesting a decline in macroautophagy during aging. In skeletal muscle from aged mice, there also was a decline in LC3B-I conjugation to phosphatidylethanolamine (PE) possibly due to decreased protein levels of ATG3 and ATG12-ATG5. The CMA markers, LAMP-2A and Hsc70, and mitochondrial turnover markers, Drp1, PINK1 and PGC1α also were decreased. Metabolomics analysis showed impaired β-oxidation in heart of aged mice, whereas increased branched-chain amino acids (BCAAs) and ceramide levels were found in skeletal muscle of aged mice that in turn, may contribute to insulin resistance in muscle. Taken together, our studies showed similar declines in macroautophagy but distinct effects on CMA, mitochondrial turnover, and metabolic dysfunction in muscle vs. heart during aging. |
| first_indexed | 2024-10-01T02:41:52Z |
| format | Journal Article |
| id | ntu-10356/102485 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T02:41:52Z |
| publishDate | 2018 |
| record_format | dspace |
| spelling | ntu-10356/1024852023-02-28T17:05:09Z Changes in macroautophagy, chaperone-mediated autophagy, and mitochondrial metabolism in murine skeletal and cardiac muscle during aging Zhou, Jin Chong, Shu Yun Lim, Andrea Singh, Brijesh K. Sinha, Rohit A. Salmon, Adam B. Yen, Paul M. School of Biological Sciences Muscle Aging DRNTU::Science::Biological sciences Aging causes a general decline in cellular metabolic activity, and function in different tissues and whole body homeostasis. However, the understanding about the metabolomic and autophagy changes in skeletal muscle and heart during aging is still limited. We thus examined markers for macroautophagy, chaperone-mediated autophagy (CMA), mitochondrial quality control, as well as cellular metabolites in skeletal and cardiac muscle from young (5 months old) and aged (27 months old) mice. We found decreased autophagic degradation of p62 and increased ubiquitinated proteins in both tissues from aged mice, suggesting a decline in macroautophagy during aging. In skeletal muscle from aged mice, there also was a decline in LC3B-I conjugation to phosphatidylethanolamine (PE) possibly due to decreased protein levels of ATG3 and ATG12-ATG5. The CMA markers, LAMP-2A and Hsc70, and mitochondrial turnover markers, Drp1, PINK1 and PGC1α also were decreased. Metabolomics analysis showed impaired β-oxidation in heart of aged mice, whereas increased branched-chain amino acids (BCAAs) and ceramide levels were found in skeletal muscle of aged mice that in turn, may contribute to insulin resistance in muscle. Taken together, our studies showed similar declines in macroautophagy but distinct effects on CMA, mitochondrial turnover, and metabolic dysfunction in muscle vs. heart during aging. NMRC (Natl Medical Research Council, S’pore) Published version 2018-12-27T08:55:07Z 2019-12-06T20:55:38Z 2018-12-27T08:55:07Z 2019-12-06T20:55:38Z 2017 Journal Article Zhou, J., Chong, S. Y., Lim, A., Singh, B. K., Sinha, R. A., Salmon, A. B., & Yen, P. M. (2017). Changes in macroautophagy, chaperone-mediated autophagy, and mitochondrial metabolism in murine skeletal and cardiac muscle during aging. Aging, 9(2), 583-599. doi:10.18632/aging.101181 https://hdl.handle.net/10356/102485 http://hdl.handle.net/10220/47261 10.18632/aging.101181 en Aging © 2017 The Author(s) (published by Impact Journals). This is an open-access article distributed under the terms of the Creative Commons Attribution License. 17 p. application/pdf |
| spellingShingle | Muscle Aging DRNTU::Science::Biological sciences Zhou, Jin Chong, Shu Yun Lim, Andrea Singh, Brijesh K. Sinha, Rohit A. Salmon, Adam B. Yen, Paul M. Changes in macroautophagy, chaperone-mediated autophagy, and mitochondrial metabolism in murine skeletal and cardiac muscle during aging |
| title | Changes in macroautophagy, chaperone-mediated autophagy, and mitochondrial metabolism in murine skeletal and cardiac muscle during aging |
| title_full | Changes in macroautophagy, chaperone-mediated autophagy, and mitochondrial metabolism in murine skeletal and cardiac muscle during aging |
| title_fullStr | Changes in macroautophagy, chaperone-mediated autophagy, and mitochondrial metabolism in murine skeletal and cardiac muscle during aging |
| title_full_unstemmed | Changes in macroautophagy, chaperone-mediated autophagy, and mitochondrial metabolism in murine skeletal and cardiac muscle during aging |
| title_short | Changes in macroautophagy, chaperone-mediated autophagy, and mitochondrial metabolism in murine skeletal and cardiac muscle during aging |
| title_sort | changes in macroautophagy chaperone mediated autophagy and mitochondrial metabolism in murine skeletal and cardiac muscle during aging |
| topic | Muscle Aging DRNTU::Science::Biological sciences |
| url | https://hdl.handle.net/10356/102485 http://hdl.handle.net/10220/47261 |
| work_keys_str_mv | AT zhoujin changesinmacroautophagychaperonemediatedautophagyandmitochondrialmetabolisminmurineskeletalandcardiacmuscleduringaging AT chongshuyun changesinmacroautophagychaperonemediatedautophagyandmitochondrialmetabolisminmurineskeletalandcardiacmuscleduringaging AT limandrea changesinmacroautophagychaperonemediatedautophagyandmitochondrialmetabolisminmurineskeletalandcardiacmuscleduringaging AT singhbrijeshk changesinmacroautophagychaperonemediatedautophagyandmitochondrialmetabolisminmurineskeletalandcardiacmuscleduringaging AT sinharohita changesinmacroautophagychaperonemediatedautophagyandmitochondrialmetabolisminmurineskeletalandcardiacmuscleduringaging AT salmonadamb changesinmacroautophagychaperonemediatedautophagyandmitochondrialmetabolisminmurineskeletalandcardiacmuscleduringaging AT yenpaulm changesinmacroautophagychaperonemediatedautophagyandmitochondrialmetabolisminmurineskeletalandcardiacmuscleduringaging |