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Caloric Restriction Reprograms Adipose Tissues in Rhesus Monkeys
Josef P Clark1, Timothy W Rhoads2, Sean J McIlwain3,4
1Department of Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Aging Cell
|October 3, 2025
Summary
Caloric restriction (CR) benefits aging by altering fat tissue. This study reveals shared and depot-specific molecular adaptations in subcutaneous and visceral fat in monkeys, offering insights into conserved aging processes.
Area of Science:
- Gerontology
- Metabolic Research
- Molecular Biology
Background:
- Caloric restriction (CR) is a dietary intervention known to extend lifespan and delay age-related diseases across various species.
- Adipose tissues play a role in CR's benefits, but the underlying molecular mechanisms remain largely unelucidated.
- Understanding fat tissue adaptations to CR is crucial for developing strategies to combat aging and associated diseases.
Purpose of the Study:
- To investigate the molecular adaptations in subcutaneous and visceral adipose depots in response to long-term caloric restriction.
- To identify shared and depot-specific changes in gene expression and pathways influenced by CR.
- To compare these adaptations between monkeys and humans to assess evolutionary conservation.
Main Methods:
- Analysis of gene expression profiles in subcutaneous and visceral adipose tissues from aged male rhesus monkeys subjected to life-long CR.
- Differential gene expression analysis to identify significant molecular changes.
- Pathway analysis to understand the biological processes affected by CR in different fat depots.
Main Results:
- Life-long CR induced both shared and depot-specific molecular adaptations in subcutaneous and visceral adipose depots.
- RNA processing and proteostasis pathways were commonly enriched in both fat depots under CR.
- Metabolic, growth, and inflammatory pathways showed depot-specific alterations in response to CR.
- Observed adaptations in rhesus monkeys share commonalities with human responses, indicating conserved mechanisms.
Conclusions:
- Adipose tissue adaptations to CR exhibit significant depot-specificity, reflecting functional differences between fat depots.
- CR-induced changes in RNA processing and proteostasis are conserved across different fat depots.
- The depot-specific responses in metabolic and inflammatory pathways highlight distinct roles in aging and disease vulnerability.
- These findings provide molecular insights into the conserved effects of CR on aging and suggest potential therapeutic targets.
