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Transcriptome analysis of fibroblast subpopulations isolated from neonatal murine dermis.

ABSTRACT: During aging, stromal functions are thought to be impaired, yet little is known whether this stems from molecular and cellular changes of fibroblasts, a major component of stroma. Using population- and single-cell whole transcriptomics, and long-term lineage tracing, we studied alterations in murine dermal fibroblasts during physiological aging under different dietary regimes known to affect longevity. We show that the identity of aged fibroblasts becomes undefined, with the distinct fibroblast states present in young skin no longer clearly demarcated. In addition, old fibroblasts not only reduce the expression of genes involved in the formation of the extracellular matrix, but intriguingly, also gain adipogenic traits, paradoxically becoming similar to neonatal pro-adipogenic fibroblasts. These age-related alterations are sensitive to systemic changes in metabolism: long-term caloric restriction prevents them in old fibroblasts in a reversible manner, whereas a high-fat diet potentiates them in young fibroblasts. Finally, inhibition of the master regulator of adipogenesis, PPARgamma, attenuates fibroblast aging in vivo, providing potential anti-aging therapeutic alternatives to caloric restriction.

ORGANISM(S): Mus musculus

PROVIDER: GSE110979 | GEO | 2018/11/14

REPOSITORIES: GEO

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The effect of caloric restriction on the transcriptome of dermal fibroblasts during aging

Project description:During aging, stromal functions are thought to be impaired, yet little is known whether this stems from molecular and cellular changes of fibroblasts, a major component of stroma. Using population- and single-cell whole transcriptomics, and long-term lineage tracing, we studied alterations in murine dermal fibroblasts during physiological aging under different dietary regimes known to affect longevity. We show that the identity of aged fibroblasts becomes undefined, with the distinct fibroblast states present in young skin no longer clearly demarcated. In addition, old fibroblasts not only reduce the expression of genes involved in the formation of the extracellular matrix, but intriguingly, also gain adipogenic traits, paradoxically becoming similar to neonatal pro-adipogenic fibroblasts. These age-related alterations are sensitive to systemic changes in metabolism: long-term caloric restriction prevents them in old fibroblasts in a reversible manner, whereas a high-fat diet potentiates them in young fibroblasts. Finally, inhibition of the master regulator of adipogenesis, PPARgamma, attenuates fibroblast aging in vivo, providing potential anti-aging therapeutic alternatives to caloric restriction.

2018-11-14 | GSE110982 | GEO

The effect of high fat diet on the transcriptome of murine dermal fibroblasts

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The effect of topical PPARG inhibitor (GW9662) treatment on the transcriptome of old dermal fibroblasts

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Impact of aging/caloric restriction on circadian gene expression

Project description:Transcriptome analysis using the liver from young versus old mice, fed either normally or under caloric restriction reveals reorganization of distinct circadian signatures related to metabolic aging and nutrient-dependent counterbalance of aging by caloric restriction

2017-07-21 | GSE93903 | GEO

Differential expression of microRNAs in adipose tissue with aging and caloric restriction

Project description:To further analyze the effect of aging and caloric restriction in the microRNA expression, we have employed microarray expression profiling as a discovery platform to identify differentially expressed microRNAs in middle-aged animals and the impact of caloric restriction in the microRNA expression profile. Subcutaneous and visceral adipose tissue were extracted from 3 groups of mice: 3 month-old, 12 month-old fed ad libitum and 12 month-old fed with a caloric restricted diet. Comparisons between young and middle-aged animals in subcutaneous and visceral adipose tissue, and between the 12 month old ad libitum and 12 month old caloric restricted diet in both adipose depots were made.

2022-11-30 | GSE217353 | GEO

Phosphoproteomic analysis reveals enhanced PKA signaling in aged skeletal muscle is suppressed by caloric restriction

Project description:Although caloric restriction (CR) was first shown to extend the lifespan of rodents over 75 years ago, the underlying mechanisms remain unclear. Additionally, the majority of published studies have focused on the effects of short-term CR. To better understand cell signaling alterations in a tissue known to be highly impacted by CR, we sought to assess the impact of aging and lifelong CR on skeletal muscle protein phosphorylation dynamics. We performed phosphoproteomic analysis on skeletal muscle from young mice, old mice fed on an ad libitum diet, and old mice fed a CR diet. This analysis revealed distinct phosphoproteomic signatures associated with both aging and diet. Importantly, CR appeared to promote a signature that was more similar to young mice than old mice fed on an ad lib diet. From the phosphorylation measurements on its known substrates, we deciphered that aging promotes Protein kinase A (PKA) signaling, and CR inhibits this signaling cascade. Given the demonstrated role of PKA signaling as a “pro-aging” pathway in various model organisms, including yeast and mice, we propose that CR exerts its longevity-enhancing effects partially via the suppression of this pathway.

2021-01-30 | PXD018455 | JPOST Repository

Differences in genome-wide gene expression response in PBMCs between young and old men upon caloric restriction

Project description:Caloric restriction (CR) is considered to increase lifespan and to prevent various age-related diseases in different non-human organisms. Only a limited number of CR studies have been performed in humans, and results put CR as a beneficial tool to decrease risk factors in several age-related diseases. The question remains at what age CR should be implemented to be most effective with respect to healthy aging. The aim of our study was to elucidate the role of age in the transcriptional response to a 30% CR diet in immune cells, as immune response is affected during aging. Ten healthy young men, aged 20-34, and nine healthy old men, aged 64-85, were subjected to a two week weight maintenance diet, followed by three weeks of 30% CR. Before and after 30% CR, peripheral blood mononuclear cellsâ (PBMCs) whole genome gene expression was assessed. Expression of 554 genes showed a different response between young and old men upon CR. Gene set enrichment analysis revealed a downregulation of gene sets involved in immune response in young men, but not in old men. At baseline, immune response-related genes were already higher expressed in old compared to young men. Upstream regulator analyses revealed that most potential regulators were controlling immune response, and were inhibited in young men upon CR, and activated in old men at baseline. Based on the gene expression data, we conclude that a short period of CR is more effective in young men compared to old men regarding immune related pathways. Gene expression was profiled in peripheral blood mononuclear cells (PBMCs) from young and old men before and after 30% caloric restriction.

2016-10-24 | E-GEOD-63117 | biostudies-arrayexpress

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