GO:0061771 response to caloric restriction: Metabolic Stress Response, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0061771 (response to caloric restriction) describes the cellular and organismal changes triggered by insufficient food energy intake, including shifts in gene expression, secretion, enzyme production and movement.
• Caloric restriction (CR) and fasting regimes remodel systemic proteomes, gut microbiome composition and immune-metabolic signaling in humans and animal models.
• Autophagy is a central downstream response to caloric restriction, with both beneficial and potentially adverse effects depending on context and duration.
• Dietary restriction extends healthspan and lifespan in genetically diverse mice, but the magnitude of benefit is genotype-dependent.
• Caloric restriction can exert anti-cancer effects partly through remodeling of tumor-infiltrating neutrophils and lipid accumulation.
• CR research spans proteomics, metabolomics, microbiome sequencing, autophagy flux assays and CRISPR-based functional genomics.
Description
GO:0061771, response to caloric restriction, is a biological process Gene Ontology term that captures the change in state or activity of a cell or organism as a result of caloric restriction, defined as insufficient food energy intake. This term encompasses a wide range of cellular outputs, including altered gene expression, enzyme production, secretion and movement, that collectively allow an organism to adapt to reduced energy availability. Because caloric restriction is one of the most reproducible non-genetic interventions affecting healthspan and metabolism, GO:0061771 serves as a conceptual anchor for researchers integrating molecular, physiological and clinical data.
response to caloric restriction At A Glance
| GO ID | GO:0061771 |
|---|---|
| GO term | response to caloric restriction |
| Ontology | biological_process |
| Synonym | none |
| Definition | A change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a caloric restriction, insufficient food energy intake. |
| Major function | Coordinated cellular and organismal adaptation to reduced energy intake, including metabolic, autophagic, immune and endocrine responses. |
| Related processes | Autophagy, intermittent fasting responses, dietary restriction, metabolic remodeling, immune-metabolic signaling. |
| Typical experimental triggers | Caloric restriction diets, fasting, intermittent fasting, protein pacing with intermittent fasting. |
| Key research readouts | Proteome remodeling, metabolomic profiles, gut microbiome composition, autophagy flux, gene expression changes. |
What Is GO:0061771?
In practical terms, GO:0061771 describes any measurable change in a cell or organism that occurs because of caloric restriction. The QuickGO definition specifies that this includes changes in movement, secretion, enzyme production, gene expression and similar activities triggered by insufficient food energy intake. It is a biological process term, meaning it describes a program of events rather than a single molecular function or cellular component. Researchers use this term to annotate datasets in which reduced calorie intake is the experimental variable, such as fasting studies, dietary restriction trials and intermittent fasting models.
Why Is response to caloric restriction Important in Cell Biology?
Understanding GO:0061771 is important because caloric restriction is one of the few interventions that reproducibly influences metabolism, immunity and lifespan across species, and because its effects are highly context- and genotype-dependent. The term provides a standardized way to annotate and compare datasets from fasting, intermittent fasting and continuous caloric restriction studies, which increasingly combine proteomics, metabolomics and microbiome profiling. It also connects mechanistic cell biology, such as autophagy regulation, to clinical questions in cancer, metabolic disease and aging.
• Caloric restriction and fasting regimes are widely studied for their effects on healthspan and lifespan in model organisms and humans.
• Autophagic responses to caloric restriction can be beneficial or adverse depending on duration and tissue context.
• Systemic proteome adaptions to complete caloric restriction reveal coordinated multi-organ responses in humans.
• Gut microbiome remodeling and metabolomic changes occur in response to intermittent fasting and continuous caloric restriction.
• Intermittent fasting influences both immunity and metabolism, linking GO:0061771 to immune-metabolic research.
• Intermittent fasting is studied in both health and disease contexts, including metabolic and inflammatory conditions.
• Caloric restriction can induce anti-cancer effects partly through restricting lipid accumulation in tumor-infiltrating neutrophils.
• Dietary interventions and precision nutrition are being explored as adjuncts in cancer therapy.
• Genotype-dependent responses to dietary restriction highlight the need for functional genomics approaches.
What Happens During response to caloric restriction?
Sensing reduced energy intake
In simple terms: When calories are limited, cells first notice that fuel is scarce.
The initial step in response to caloric restriction is the sensing of reduced energy availability, which triggers changes in systemic and cellular signaling. In humans, 7-day complete caloric restriction leads to coordinated proteome adaptions across multiple organs, indicating that energy sensing is a systemic process rather than a cell-autonomous event. These early responses set the stage for downstream metabolic and immune remodeling.
Autophagic and metabolic remodeling
In simple terms: Cells start recycling their own components and shifting how they make and use energy.
A central feature of the response to caloric restriction is the activation of autophagy, a process that can have both beneficial and adverse effects depending on context. Autophagic flux assays and metabolic profiling in fasting and caloric restriction models show that cells adjust enzyme production and substrate use to maintain energy balance. This remodeling is closely tied to changes in gene expression and secretion that are annotated under GO:0061771.
Immune and microbiome responses
In simple terms: The gut bacteria and immune system also change when calories are restricted.
Caloric restriction and intermittent fasting remodel the gut microbiome and metabolomic profile, as shown in studies comparing protein pacing with intermittent fasting versus continuous caloric restriction. Intermittent fasting also influences immunity and metabolism, linking GO:0061771 to immune cell function and inflammatory signaling. In cancer models, caloric restriction can restrict lipid accumulation in tumor-infiltrating neutrophils, contributing to anti-cancer effects.
Long-term physiological outcomes
In simple terms: Over time, these changes can affect health and lifespan, but the size of the effect depends on genetics.
Dietary restriction impacts health and lifespan in genetically diverse mice, with the magnitude of benefit varying by genotype. This suggests that the response to caloric restriction is not uniform and that genetic background shapes the downstream physiological outcomes. Dietary interventions and precision nutrition are therefore being explored as personalized strategies in cancer therapy and metabolic disease.
Key Genes Involved in GO:0061771 response to caloric restriction
The genes and proteins below are representative of pathways and processes that have been linked to caloric restriction responses in the cited literature, including autophagy, metabolic signaling, immune regulation and microbiome-related metabolism.
| Gene | Major Role | Research Relevance |
|---|---|---|
| MAP1LC3B | Autophagy marker involved in autophagosome formation | Used to monitor autophagic response to caloric restriction |
| BECN1 | Core autophagy regulator | Studied in fasting and caloric restriction models |
| MTOR | Central nutrient-sensing kinase | Key regulator of metabolic response to caloric restriction |
| FOXO3 | Transcription factor linked to longevity and stress response | Investigated in dietary restriction and lifespan studies |
| SIRT1 | NAD-dependent deacetylase involved in metabolic regulation | Studied in caloric restriction and fasting responses |
| PPARGC1A | Transcriptional coactivator regulating mitochondrial biogenesis | Used as a readout of metabolic remodeling |
| LEP | Leptin, a key energy-balance hormone | Measured in caloric restriction and fasting studies |
| ADIPOQ | Adiponectin, involved in glucose and lipid metabolism | Profiled in systemic proteome adaptions to caloric restriction |
| IGF1 | Growth factor linked to nutrient sensing and longevity | Studied in dietary restriction and lifespan experiments |
| IL6 | Cytokine linking immunity and metabolism | Assessed in intermittent fasting and immune-metabolic studies |
| TNF | Inflammatory cytokine | Measured in caloric restriction and immune response studies |
| CXCL8 | Neutrophil-recruiting chemokine | Relevant to neutrophil lipid accumulation in cancer under caloric restriction |
| FABP4 | Lipid chaperone in adipocytes and macrophages | Linked to lipid accumulation in tumor-infiltrating neutrophils |
| CPT1A | Fatty acid oxidation enzyme | Used to assess metabolic shifts during caloric restriction |
| HIF1A | Hypoxia-inducible factor linked to metabolism | Studied in tumor and immune-metabolic contexts |
| NFE2L2 | Oxidative stress response transcription factor | Investigated in dietary restriction and stress resistance |
| TP53 | Tumor suppressor and stress response regulator | Relevant to caloric restriction and cancer studies |
| INS | Insulin, central to glucose homeostasis | Measured in caloric restriction and fasting interventions |
How Is response to caloric restriction Regulated?
The response to caloric restriction is regulated by nutrient-sensing pathways, most notably mTOR signaling, which integrates energy availability with autophagy and metabolic remodeling. Autophagic responses to caloric restriction are tightly controlled and can be beneficial or adverse depending on duration and tissue context. Immune-metabolic regulation also plays a role, as intermittent fasting influences immunity and metabolism through cytokine and metabolic signaling. Systemic proteome adaptions to complete caloric restriction further indicate multi-organ regulatory coordination.
response to caloric restriction and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| FABP4 | Lipid accumulation in tumor-infiltrating neutrophils under caloric restriction | Knockout or point-mutation models in cancer cell lines and mouse tumor models |
| MTOR | Metabolic and immune regulation in fasting and caloric restriction | Knock-in or point-mutation models to modulate mTOR activity |
| MAP1LC3B | Autophagy flux in caloric restriction and fasting | Tagged knock-in reporter for autophagy monitoring |
| IL6 | Immune-metabolic signaling in intermittent fasting | Knockout and overexpression models in immune cells |
| FOXO3 | Longevity and dietary restriction responses | Knockout and knock-in models in genetically diverse mice |
Cancer and tumor metabolism
Caloric restriction can exert anti-cancer effects partly by restricting lipid accumulation in tumor-infiltrating neutrophils, as shown in preclinical models. Dietary interventions and precision nutrition are being explored as adjunct strategies in cancer therapy, with the goal of modulating tumor metabolism and immune responses. These findings link GO:0061771 to cancer biology and suggest that caloric restriction responses in immune cells may be therapeutically relevant.
Metabolic and immune disorders
Intermittent fasting and caloric restriction influence both immunity and metabolism, making GO:0061771 relevant to metabolic and inflammatory conditions. Gut microbiome remodeling and metabolomic changes in response to protein pacing with intermittent fasting versus continuous caloric restriction suggest that dietary patterns can shape host-microbe interactions. Intermittent fasting is studied in both health and disease contexts, including metabolic and inflammatory disorders.
Aging and lifespan regulation
Dietary restriction impacts health and lifespan in genetically diverse mice, but the effect size depends on genotype. This genotype-dependent response highlights the need for functional genomics approaches to identify which genes mediate the beneficial or adverse effects of caloric restriction. Autophagic responses to caloric restriction may contribute to these lifespan effects, although the balance between beneficial and adverse autophagy remains context-dependent.
From response to caloric restriction-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does a candidate gene mediate autophagic response to caloric restriction? | Knockout cell model with autophagy flux readouts |
| Does a specific point mutation alter nutrient-sensing kinase activity? | Point-mutation knock-in cell model |
| Can a reporter gene track caloric restriction-induced transcription? | Knock-in reporter cell line |
| Does overexpression of a metabolic gene mimic caloric restriction effects? | Overexpression cell model |
| Which genes are required for immune-metabolic remodeling during fasting? | CRISPR library screening in immune cells |
| How does genotype influence dietary restriction outcomes? | Genetically diverse mouse models with targeted edits |
How to Study the response to caloric restriction Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Proteomics | Systemic protein abundance changes | Mapping multi-organ adaptions to caloric restriction |
| Metabolomics | Small-molecule metabolite profiles | Comparing intermittent fasting and continuous caloric restriction |
| Autophagy flux assay | Autophagic degradation activity | Assessing beneficial vs adverse autophagy in fasting |
| 16S rRNA sequencing | Gut microbiome composition | Studying microbiome remodeling during caloric restriction |
| Cytokine profiling | Immune signaling molecules | Linking intermittent fasting to immunity |
| CRISPR library screening | Gene essentiality and fitness | Identifying regulators of caloric restriction responses |
| RNA-seq | Transcriptome changes | Measuring gene expression under caloric restriction |
| Lipid staining and imaging | Lipid accumulation in cells | Analyzing tumor-infiltrating neutrophils under caloric restriction |
Proteomics and metabolomics
Systemic proteome adaptions to 7-day complete caloric restriction in humans have been mapped using proteomic approaches, revealing multi-organ responses. Metabolomic profiling in intermittent fasting and continuous caloric restriction studies provides complementary information on small-molecule changes. These methods are essential for annotating datasets under GO:0061771.
Autophagy flux assays
Autophagic responses to caloric restriction and fasting can be monitored using autophagy flux assays, which distinguish between beneficial and adverse autophagy. These assays often use LC3-based reporters and lysosomal inhibitors to measure flux rather than steady-state levels.
Microbiome and immune profiling
Gut microbiome remodeling in response to intermittent fasting and continuous caloric restriction is studied using 16S rRNA or metagenomic sequencing. Immune profiling, including cytokine measurements and neutrophil lipid analysis, links caloric restriction to immune-metabolic outcomes.
Functional genomics and CRISPR screening
CRISPR library screening can identify genes required for caloric restriction responses, such as autophagy regulators or metabolic enzymes. Bioinformatics analysis of screening data helps prioritize candidate genes for follow-up knockout or knock-in studies.
How CRISPR Can Be Used to Study GO:0061771 response to caloric restriction
Knockout
CRISPR knockout models are used to test whether a candidate gene is required for the response to caloric restriction, such as autophagy regulators or metabolic enzymes. Knockout cell lines can be subjected to fasting-mimicking conditions and analyzed by autophagy flux, RNA-seq or proteomics.
Point Mutation
Point-mutation knock-in models allow researchers to dissect specific phosphorylation or catalytic sites in nutrient-sensing proteins like mTOR or metabolic enzymes. These models help distinguish between different signaling outputs of the same gene during caloric restriction.
Knock-in
Knock-in reporter lines, such as fluorescent autophagy reporters, enable real-time monitoring of caloric restriction responses in live cells. Knock-in of disease-associated variants can also reveal how genetic background modifies the response to dietary restriction.
Overexpression
Overexpression models are used to test whether increasing a gene's activity is sufficient to mimic or enhance caloric restriction effects, such as lipid restriction in immune cells. These models complement knockout studies by providing gain-of-function evidence.
How EDITGENE Supports response to caloric restriction Research
Researchers studying response to caloric restriction-related genes often need to determine whether a candidate gene is causally involved in the metabolic, autophagic or immune changes triggered by reduced energy intake. EDITGENE provides CRISPR-based cell model services that enable functional validation of such candidate genes in relevant cell types.
Contact EDITGENE today to design your custom CRISPR model for response to caloric restriction research.
Frequently Asked Questions About response to caloric restriction
What is GO:0061771?
GO:0061771 is the Gene Ontology term for response to caloric restriction, defined as a change in state or activity of a cell or organism as a result of insufficient food energy intake.
What genes are involved in response to caloric restriction?
Genes involved include autophagy regulators such as MAP1LC3B and BECN1, nutrient sensors such as MTOR, and metabolic and immune genes such as FOXO3, SIRT1, IL6 and FABP4.
How does caloric restriction affect autophagy?
Caloric restriction and fasting can induce autophagic responses that may be beneficial or adverse depending on context, and these are studied using autophagy flux assays.
Does caloric restriction affect the gut microbiome?
Yes, studies show gut microbiome remodeling and metabolomic changes in response to intermittent fasting and continuous caloric restriction.
Can caloric restriction influence immunity?
Intermittent fasting influences immunity and metabolism, and caloric restriction can affect tumor-infiltrating neutrophils and lipid accumulation.
Does caloric restriction extend lifespan?
Dietary restriction impacts health and lifespan in genetically diverse mice, but the magnitude of benefit is genotype-dependent.
What methods are used to study response to caloric restriction?
Common methods include proteomics, metabolomics, autophagy flux assays, microbiome sequencing, cytokine profiling and CRISPR screening.
How can CRISPR help study GO:0061771?
CRISPR knockout, point-mutation, knock-in and overexpression models allow functional testing of candidate genes in caloric restriction responses.
Is caloric restriction relevant to cancer therapy?
Dietary interventions and precision nutrition are being explored in cancer therapy, and caloric restriction can have anti-cancer effects in preclinical models.
What is the difference between caloric restriction and intermittent fasting?
Both reduce energy intake, but intermittent fasting involves alternating periods of fasting and eating, while continuous caloric restriction reduces daily intake; both are studied under GO:0061771.
Conclusion
GO:0061771 response to caloric restriction captures a broad and clinically relevant biological process that integrates metabolism, autophagy, immunity and microbiome biology. The cited literature shows that caloric restriction triggers systemic proteome adaptions, autophagic responses, immune-metabolic changes and genotype-dependent effects on health and lifespan. Researchers can leverage CRISPR-based cell models and functional genomics to dissect the causal genes and pathways underlying these responses.
References
- 1. Shabkhizan R et al.. 2023. The Beneficial and Adverse Effects of Autophagic Response to Caloric Restriction and Fasting.. Adv Nutr 14(5):1211-1225 PMID: 37527766
- 2. Pietzner M et al.. 2024. Systemic proteome adaptions to 7-day complete caloric restriction in humans.. Nat Metab 6(4):764-777 PMID: 38429390
- 3. Mohr AE et al.. 2024. Gut microbiome remodeling and metabolomic profile improves in response to protein pacing with intermittent fasting versus continuous caloric restriction.. Nat Commun 15(1):4155 PMID: 38806467
- 4. Marko DM et al.. 2024. Intermittent fasting influences immunity and metabolism.. Trends Endocrinol Metab 35(9):821-833 PMID: 38719726
- 5. Mishra A et al.. 2024. Intermittent fasting in health and disease.. Arch Physiol Biochem 130(6):755-767 PMID: 37828854
- 6. Gao J et al.. 2026. Restricting lipid accumulation in tumor-infiltrating neutrophils mediates caloric restriction-induced anti-cancer effects.. Cell Metab 38(3):598-615.e7 PMID: 41352341
- 7. Martínez-Garay C et al.. 2023. Dietary interventions and precision nutrition in cancer therapy.. Trends Mol Med 29(7):489-511 PMID: 37263858
- 8. Di Francesco A et al.. 2024. Dietary restriction impacts health and lifespan of genetically diverse mice.. Nature 634(8034):684-692 PMID: 39385029
