Mitochondrial respiration atlas reveals differential changes in mitochondrial function across sex and age
Organ function declines with age, and large-scale transcriptomic analyses have highlighted differential aging trajectories across tissues. The mechanism underlying shared and organ-selective functional changes across the lifespan, however, still remains poorly understood. Given the central role of m...
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eLife Sciences Publications Ltd
2024-12-01
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| Online Access: | https://elifesciences.org/articles/96926 |
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| author | Dylan C Sarver Muzna Saqib Fangluo Chen G William Wong |
| author_facet | Dylan C Sarver Muzna Saqib Fangluo Chen G William Wong |
| author_sort | Dylan C Sarver |
| collection | DOAJ |
| description | Organ function declines with age, and large-scale transcriptomic analyses have highlighted differential aging trajectories across tissues. The mechanism underlying shared and organ-selective functional changes across the lifespan, however, still remains poorly understood. Given the central role of mitochondria in powering cellular processes needed to maintain tissue health, we therefore undertook a systematic assessment of respiratory activity across 33 different tissues in young (2.5 months) and old (20 months) mice of both sexes. Our high-resolution mitochondrial respiration atlas reveals: (1) within any group of mice, mitochondrial activity varies widely across tissues, with the highest values consistently seen in heart, brown fat, and kidney; (2) biological sex is a significant but minor contributor to mitochondrial respiration, and its contributions are tissue-specific, with major differences seen in the pancreas, stomach, and white adipose tissue; (3) age is a dominant factor affecting mitochondrial activity, especially across most brain regions, different fat depots, skeletal muscle groups, eyes, and different regions of the gastrointestinal tract; (4) age effects can be sex- and tissue-specific, with some of the largest effects seen in pancreas, heart, adipose tissue, and skeletal muscle; and (5) while aging alters the functional trajectories of mitochondria in a majority of tissues, some are remarkably resilient to age-induced changes. Altogether, our data provide the most comprehensive compendium of mitochondrial respiration and illuminate functional signatures of aging across diverse tissues and organ systems. |
| format | Article |
| id | doaj-art-bbc00e49006b410db17d596fde5c9eb2 |
| institution | OA Journals |
| issn | 2050-084X |
| language | English |
| publishDate | 2024-12-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj-art-bbc00e49006b410db17d596fde5c9eb22025-08-20T02:34:49ZengeLife Sciences Publications LtdeLife2050-084X2024-12-011310.7554/eLife.96926Mitochondrial respiration atlas reveals differential changes in mitochondrial function across sex and ageDylan C Sarver0Muzna Saqib1Fangluo Chen2G William Wong3https://orcid.org/0000-0002-5286-6506Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, United States; Center for Metabolism and Obesity Research, Johns Hopkins University School of Medicine, Baltimore, United StatesDepartment of Physiology, Johns Hopkins University School of Medicine, Baltimore, United States; Center for Metabolism and Obesity Research, Johns Hopkins University School of Medicine, Baltimore, United StatesDepartment of Physiology, Johns Hopkins University School of Medicine, Baltimore, United States; Center for Metabolism and Obesity Research, Johns Hopkins University School of Medicine, Baltimore, United StatesDepartment of Physiology, Johns Hopkins University School of Medicine, Baltimore, United States; Center for Metabolism and Obesity Research, Johns Hopkins University School of Medicine, Baltimore, United StatesOrgan function declines with age, and large-scale transcriptomic analyses have highlighted differential aging trajectories across tissues. The mechanism underlying shared and organ-selective functional changes across the lifespan, however, still remains poorly understood. Given the central role of mitochondria in powering cellular processes needed to maintain tissue health, we therefore undertook a systematic assessment of respiratory activity across 33 different tissues in young (2.5 months) and old (20 months) mice of both sexes. Our high-resolution mitochondrial respiration atlas reveals: (1) within any group of mice, mitochondrial activity varies widely across tissues, with the highest values consistently seen in heart, brown fat, and kidney; (2) biological sex is a significant but minor contributor to mitochondrial respiration, and its contributions are tissue-specific, with major differences seen in the pancreas, stomach, and white adipose tissue; (3) age is a dominant factor affecting mitochondrial activity, especially across most brain regions, different fat depots, skeletal muscle groups, eyes, and different regions of the gastrointestinal tract; (4) age effects can be sex- and tissue-specific, with some of the largest effects seen in pancreas, heart, adipose tissue, and skeletal muscle; and (5) while aging alters the functional trajectories of mitochondria in a majority of tissues, some are remarkably resilient to age-induced changes. Altogether, our data provide the most comprehensive compendium of mitochondrial respiration and illuminate functional signatures of aging across diverse tissues and organ systems.https://elifesciences.org/articles/96926mitochondriarespiration atlassexaging |
| spellingShingle | Dylan C Sarver Muzna Saqib Fangluo Chen G William Wong Mitochondrial respiration atlas reveals differential changes in mitochondrial function across sex and age eLife mitochondria respiration atlas sex aging |
| title | Mitochondrial respiration atlas reveals differential changes in mitochondrial function across sex and age |
| title_full | Mitochondrial respiration atlas reveals differential changes in mitochondrial function across sex and age |
| title_fullStr | Mitochondrial respiration atlas reveals differential changes in mitochondrial function across sex and age |
| title_full_unstemmed | Mitochondrial respiration atlas reveals differential changes in mitochondrial function across sex and age |
| title_short | Mitochondrial respiration atlas reveals differential changes in mitochondrial function across sex and age |
| title_sort | mitochondrial respiration atlas reveals differential changes in mitochondrial function across sex and age |
| topic | mitochondria respiration atlas sex aging |
| url | https://elifesciences.org/articles/96926 |
| work_keys_str_mv | AT dylancsarver mitochondrialrespirationatlasrevealsdifferentialchangesinmitochondrialfunctionacrosssexandage AT muznasaqib mitochondrialrespirationatlasrevealsdifferentialchangesinmitochondrialfunctionacrosssexandage AT fangluochen mitochondrialrespirationatlasrevealsdifferentialchangesinmitochondrialfunctionacrosssexandage AT gwilliamwong mitochondrialrespirationatlasrevealsdifferentialchangesinmitochondrialfunctionacrosssexandage |