Age-related gene expression signatures from limb skeletal muscles and the diaphragm in mice and rats reveal common and species-specific changes
Abstract Background As a result of aging, skeletal muscle undergoes atrophy and a decrease in function. This age-related skeletal muscle weakness is known as “sarcopenia”. Sarcopenia is part of the frailty observed in humans. In order to discover treatments for sarcopenia, it is necessary to determi...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-07-01
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| Series: | Skeletal Muscle |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13395-023-00321-3 |
| _version_ | 1827899559678836736 |
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| author | Tea Shavlakadze Kun Xiong Shawn Mishra Corissa McEwen Abhilash Gadi Matthew Wakai Hunter Salmon Michael J. Stec Nicole Negron Min Ni Yi Wei Gurinder S. Atwal Yu Bai David J. Glass |
| author_facet | Tea Shavlakadze Kun Xiong Shawn Mishra Corissa McEwen Abhilash Gadi Matthew Wakai Hunter Salmon Michael J. Stec Nicole Negron Min Ni Yi Wei Gurinder S. Atwal Yu Bai David J. Glass |
| author_sort | Tea Shavlakadze |
| collection | DOAJ |
| description | Abstract Background As a result of aging, skeletal muscle undergoes atrophy and a decrease in function. This age-related skeletal muscle weakness is known as “sarcopenia”. Sarcopenia is part of the frailty observed in humans. In order to discover treatments for sarcopenia, it is necessary to determine appropriate preclinical models and the genes and signaling pathways that change with age in these models. Methods and results To understand the changes in gene expression that occur as a result of aging in skeletal muscles, we generated a multi-time-point gene expression signature throughout the lifespan of mice and rats, as these are the most commonly used species in preclinical research and intervention testing. Gastrocnemius, tibialis anterior, soleus, and diaphragm muscles from male and female C57Bl/6J mice and male Sprague Dawley rats were analyzed at ages 6, 12, 18, 21, 24, and 27 months, plus an additional 9-month group was used for rats. More age-related genes were identified in rat skeletal muscles compared with mice; this was consistent with the finding that rat muscles undergo more robust age-related decline in mass. In both species, pathways associated with innate immunity and inflammation linearly increased with age. Pathways linked with extracellular matrix remodeling were also universally downregulated. Interestingly, late downregulated pathways were exclusively found in the rat limb muscles and these were linked to metabolism and mitochondrial respiration; this was not seen in the mouse. Conclusions This extensive, side-by-side transcriptomic profiling shows that the skeletal muscle in rats is impacted more by aging compared with mice, and the pattern of decline in the rat may be more representative of the human. The observed changes point to potential therapeutic interventions to avoid age-related decline in skeletal muscle function. |
| first_indexed | 2024-03-12T23:19:39Z |
| format | Article |
| id | doaj.art-a43926fa120c4d5db9e644d5c5986045 |
| institution | Directory Open Access Journal |
| issn | 2044-5040 |
| language | English |
| last_indexed | 2024-03-12T23:19:39Z |
| publishDate | 2023-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Skeletal Muscle |
| spelling | doaj.art-a43926fa120c4d5db9e644d5c59860452023-07-16T11:31:48ZengBMCSkeletal Muscle2044-50402023-07-0113111510.1186/s13395-023-00321-3Age-related gene expression signatures from limb skeletal muscles and the diaphragm in mice and rats reveal common and species-specific changesTea Shavlakadze0Kun Xiong1Shawn Mishra2Corissa McEwen3Abhilash Gadi4Matthew Wakai5Hunter Salmon6Michael J. Stec7Nicole Negron8Min Ni9Yi Wei10Gurinder S. Atwal11Yu Bai12David J. Glass13Regeneron PharmaceuticalsRegeneron PharmaceuticalsRegeneron PharmaceuticalsRegeneron PharmaceuticalsRegeneron PharmaceuticalsRegeneron PharmaceuticalsRegeneron PharmaceuticalsRegeneron PharmaceuticalsRegeneron PharmaceuticalsRegeneron PharmaceuticalsRegeneron PharmaceuticalsRegeneron PharmaceuticalsRegeneron PharmaceuticalsRegeneron PharmaceuticalsAbstract Background As a result of aging, skeletal muscle undergoes atrophy and a decrease in function. This age-related skeletal muscle weakness is known as “sarcopenia”. Sarcopenia is part of the frailty observed in humans. In order to discover treatments for sarcopenia, it is necessary to determine appropriate preclinical models and the genes and signaling pathways that change with age in these models. Methods and results To understand the changes in gene expression that occur as a result of aging in skeletal muscles, we generated a multi-time-point gene expression signature throughout the lifespan of mice and rats, as these are the most commonly used species in preclinical research and intervention testing. Gastrocnemius, tibialis anterior, soleus, and diaphragm muscles from male and female C57Bl/6J mice and male Sprague Dawley rats were analyzed at ages 6, 12, 18, 21, 24, and 27 months, plus an additional 9-month group was used for rats. More age-related genes were identified in rat skeletal muscles compared with mice; this was consistent with the finding that rat muscles undergo more robust age-related decline in mass. In both species, pathways associated with innate immunity and inflammation linearly increased with age. Pathways linked with extracellular matrix remodeling were also universally downregulated. Interestingly, late downregulated pathways were exclusively found in the rat limb muscles and these were linked to metabolism and mitochondrial respiration; this was not seen in the mouse. Conclusions This extensive, side-by-side transcriptomic profiling shows that the skeletal muscle in rats is impacted more by aging compared with mice, and the pattern of decline in the rat may be more representative of the human. The observed changes point to potential therapeutic interventions to avoid age-related decline in skeletal muscle function.https://doi.org/10.1186/s13395-023-00321-3SarcopeniaSkeletal muscle atrophyFrailtyRNA-seqAgingAging gene signature |
| spellingShingle | Tea Shavlakadze Kun Xiong Shawn Mishra Corissa McEwen Abhilash Gadi Matthew Wakai Hunter Salmon Michael J. Stec Nicole Negron Min Ni Yi Wei Gurinder S. Atwal Yu Bai David J. Glass Age-related gene expression signatures from limb skeletal muscles and the diaphragm in mice and rats reveal common and species-specific changes Skeletal Muscle Sarcopenia Skeletal muscle atrophy Frailty RNA-seq Aging Aging gene signature |
| title | Age-related gene expression signatures from limb skeletal muscles and the diaphragm in mice and rats reveal common and species-specific changes |
| title_full | Age-related gene expression signatures from limb skeletal muscles and the diaphragm in mice and rats reveal common and species-specific changes |
| title_fullStr | Age-related gene expression signatures from limb skeletal muscles and the diaphragm in mice and rats reveal common and species-specific changes |
| title_full_unstemmed | Age-related gene expression signatures from limb skeletal muscles and the diaphragm in mice and rats reveal common and species-specific changes |
| title_short | Age-related gene expression signatures from limb skeletal muscles and the diaphragm in mice and rats reveal common and species-specific changes |
| title_sort | age related gene expression signatures from limb skeletal muscles and the diaphragm in mice and rats reveal common and species specific changes |
| topic | Sarcopenia Skeletal muscle atrophy Frailty RNA-seq Aging Aging gene signature |
| url | https://doi.org/10.1186/s13395-023-00321-3 |
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