# Novel Strategy to Quantitate Delayed Aging by Caloric Restriction

> **NIH NIH R21** · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · 2022 · $298,728

## Abstract

PROJECT SUMMARY
Aging is associated with causal epigenetic changes that occur throughout the genome, as first shown in yeast
and worms. DNA methylation clocks identify CpG sites in human blood and other tissues with age-dependent
changes. All such clocks depend on linear regression algorithms or deep learning to select CpGs methylation
sites with levels that best fit chronological age; the deviation from the linear regression prediction of chronologi-
cal age for each individual is considered, by some, a measure of biological age. Such computation of biological
age has several limitations. We developed novel approach “Microscopic Imaging of Epigenetic Landscapes”
(MIEL)-clock, which is rooted in the analysis of epigenome topography at the single cell level to measure age-
dependent signature of chromatin landscape. MIEL captures patterns of nuclear staining of epigenetic marks
and employs automated microscopy and machine learning to determine multiparametric signature of cellular
state. We provide preliminary evidence for the power of MIEL-clock to successfully distinguish several types of
young and old cells in mice and man. Our preliminary experiments using Doxorubicin (DOX) treatment, and
Caloric Restriction (CR) indicate that MIEL-clock successfully detects acceleration of aging after DOX treat-
ment and slowdown of aging after CR diet. Because CR robustly and consistently increases maximum lifespan
and delays biological aging in diverse species, successfully applied CR regimen serves as an incomparable
research tool for understanding the biology of aging. Here we propose to employ CR regimens to determine
the power of MIEL-clock to quantitate slowdown of aging process and to directly compare and contrast MIEL-
clock, RNA-seq and ATAC-seq signatures of liver hepatocytes in CR and control mice. With the caveat that
one-size does not fit all, a diet optimized for genetic background and sex can be applied to beneficially impact
healthspan and longevity. Given the composition of our study, completion of Specific Aims will yield a unique
dataset directly comparing MIEL-clock to the classical genomic readouts of CR paradigm. The latter constitute
a rich data pool for molecular mining of age-associated changes and will serve to corroborate the utility of
MIEL-clock as a simple, cost effective, high throughput single-cell readout and screening platform for evaluat-
ing dietary interventions with potential to slow down the aging process and identifying small molecules mimet-
ics of CR.

## Key facts

- **NIH application ID:** 10355362
- **Project number:** 1R21AG075483-01
- **Recipient organization:** SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE
- **Principal Investigator:** ALEXEY V TERSKIKH
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $298,728
- **Award type:** 1
- **Project period:** 2022-02-15 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10355362

## Citation

> US National Institutes of Health, RePORTER application 10355362, Novel Strategy to Quantitate Delayed Aging by Caloric Restriction (1R21AG075483-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10355362. Licensed CC0.

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