# Caloric restriction-driven immunometabolic checkpoints of inflammation

> **NIH NIH R01** · YALE UNIVERSITY · 2024 · $482,888

## Abstract

PROJECT SUMMARY:
Aging is the single biggest risk factor for disease. For the first time in US history, by 2030, people aged 65 and
older will outnumber individuals under the age of 18. Over the next 20-30 years, the number of people over the
age of 65 will double to ~80 million in the US with associated healthcare costs projected to be 2 trillion dollars.
Aging induced inflammation is the major risk factor for multiple diseases including Alzheimer's disease.
Therefore, the endogenous pathways and metabolites that deactivate inflammation of aging have high clinical
impact. Caloric restriction (CR) in animals has been shown to extend lifespan and healthspan. However, the
impact of CR on immune system, and immunometabolic control of inflammation in humans is unknown. This
proposal is in response to the PA-18-823 “Analyses of CALERIE Data and Biospecimens to Elucidate
Mechanisms of Caloric Restriction (CR)-Induced Effects in Humans”. The central hypothesis. Therefore, the
Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE-II) clinical trial was
designed to test the long-term effects of 2 years of moderate CR on human physiology and predictors of
healthspan and longevity. Our preliminary data establishes that further profiling of CALERIE-II immune cell
samples, plasma and adipose tissue biopsies collected in our study is a fruitful approach to discover
mechanism of CR and identify targets that can be developed against age-associated chronic diseases. This
project will test the central hypothesis that – negative energy balance in humans integrates metabolic and
immune cells that enhances anti-inflammatory reprogramming and reveals clinically relevant CR-mimetic
targets. The long-term goal of this project is to discover CR-mimetic targets that reduced inflammation,
enhance immune response, and promote healthspan.

## Key facts

- **NIH application ID:** 10837769
- **Project number:** 5R01AG073969-03
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** VISHWA DEEP DIXIT
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $482,888
- **Award type:** 5
- **Project period:** 2022-07-01 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10837769

## Citation

> US National Institutes of Health, RePORTER application 10837769, Caloric restriction-driven immunometabolic checkpoints of inflammation (5R01AG073969-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10837769. Licensed CC0.

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