Conserved and species-specific molecular denominators in mammalian skeletal muscle aging
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ABSTRACT:
PROVIDER: PRJNA343550 | ENA |
REPOSITORIES: ENA
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Project description:Aging is a complex phenomenon involving functional decline in multiple physiological systems. We focused on skeletal muscle to identify pathways that modulate function and healthspan by global expression profiles and specific mechanisms fundamental to aging processes. Our experimental design integrated comparative analysis of mice, rats, rhesus monkeys and humans and targeted three key time points during their lifespans. Pathways related to oxidative stress, inflammation and nutrient signaling, which function collectively to affect the quality and status of mitochondria, emerged across all species with age. Notably, mitochondrial transcript levels were better preserved in aging human muscle, suggesting an evolution-driven fitness more robust than in other species. The identification of these conserved pathways uncovers common molecular mechanisms intrinsic to health and lifespan, while unveiling of species-specific pathways emphasizes the importance of human studies for devising optimal therapeutic modalities to slow the aging process.
2017-09-20 | GSE87107 | GEO
Project description:Aging is a complex phenomenon involving functional decline in multiple physiological systems. We focused on skeletal muscle to identify pathways that modulate function and healthspan by global expression profiles and specific mechanisms fundamental to aging processes. Our experimental design integrated comparative analysis of mice, rats, rhesus monkeys and humans and targeted three key time points during their lifespans. Pathways related to oxidative stress, inflammation and nutrient signaling, which function collectively to affect the quality and status of mitochondria, emerged across all species with age. Notably, mitochondrial transcript levels were better preserved in aging human muscle, suggesting an evolution-driven fitness more robust than in other species. The identification of these conserved pathways uncovers common molecular mechanisms intrinsic to health and lifespan, while unveiling of species-specific pathways emphasizes the importance of human studies for devising optimal therapeutic modalities to slow the aging process.
2017-09-20 | GSE87108 | GEO
Project description:Aging is a complex phenomenon involving functional decline in multiple physiological systems. We focused on skeletal muscle to identify pathways that modulate function and healthspan by global expression profiles and specific mechanisms fundamental to aging processes. Our experimental design integrated comparative analysis of mice, rats, rhesus monkeys and humans and targeted three key time points during their lifespans. Pathways related to oxidative stress, inflammation and nutrient signaling, which function collectively to affect the quality and status of mitochondria, emerged across all species with age. Notably, mitochondrial transcript levels were better preserved in aging human muscle, suggesting an evolution-driven fitness more robust than in other species. The identification of these conserved pathways uncovers common molecular mechanisms intrinsic to health and lifespan, while unveiling of species-specific pathways emphasizes the importance of human studies for devising optimal therapeutic modalities to slow the aging process.
2017-09-20 | GSE87105 | GEO
Project description:Aging is a complex phenomenon involving functional decline in multiple physiological systems. We focused on skeletal muscle to identify pathways that modulate function and healthspan by global expression profiles and specific mechanisms fundamental to aging processes. Our experimental design integrated comparative analysis of mice, rats, rhesus monkeys and humans and targeted three key time points during their lifespans. Pathways related to oxidative stress, inflammation and nutrient signaling, which function collectively to affect the quality and status of mitochondria, emerged across all species with age. Notably, mitochondrial transcript levels were better preserved in aging human muscle, suggesting an evolution-driven fitness more robust than in other species. The identification of these conserved pathways uncovers common molecular mechanisms intrinsic to health and lifespan, while unveiling of species-specific pathways emphasizes the importance of human studies for devising optimal therapeutic modalities to slow the aging process.
2017-09-20 | GSE87106 | GEO
Project description:Aging is a complex phenomenon involving functional decline in multiple physiological systems. We undertook a comparative analysis of skeletal muscle from four different species, i.e. mice, rats, rhesus monkeys, and humans, at three different representative stages during their lifespan (young, middle, and old) to identify pathways that modulate function and healthspan. Gene expression profiling and computational analysis revealed that pathway complexity increases from mice to humans, and as mammals age, there is predominantly an upregulation of pathways in all species. Two downregulated pathways, the electron transport chain and oxidative phosphorylation, were common among all four species in response to aging. Quantitative PCR, biochemical analysis, mitochondrial DNA measurements, and electron microscopy revealed a conserved age-dependent decrease in mitochondrial content, and a reduction in oxidative phosphorylation complexes in monkeys and humans. Western blot analysis of key proteins in mitochondrial biogenesis discovered that (i) an imbalance toward mitochondrial fusion occurs in aged skeletal muscle and (ii) mitophagy is not overtly affected, presumably leading to the observed accumulation of abnormally large, damaged mitochondria with age. Select transcript expression analysis uncovered that the skeletal inflammatory profile differentially increases with age, but is most pronounced in humans, while increased oxidative stress (as assessed by protein carbonyl adducts and 4-hydroxynonenal) is common among all species. Expression studies also found that there is unique dysregulation of the nutrient sensing pathways among the different species with age. The identification of conserved pathways indicates common molecular mechanisms intrinsic to health and lifespan, whereas the recognition of species-specific pathways emphasizes the importance of human studies for devising optimal therapeutic modalities to slow the aging process.
| S-EPMC5460213 | biostudies-literature
Project description:Conserved and species specific molecular denominators in mammalian aging [mouse]
| PRJNA343556 | ENA
Project description:Conserved and species specific molecular denominators in mammalian aging [rat]
| PRJNA343555 | ENA
Project description:Conserved and species specific molecular denominators in mammalian aging [human]
| PRJNA343553 | ENA
Project description:Conserved and species specific molecular denominators in mammalian aging [rhesus monkey]
| PRJNA343554 | ENA