# Phenotypic Screening for Longevity Interventions Using Single-cell Epigenetic Signatures

> **NIH NIH R21** · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · 2020 · $292,500

## Abstract

PROJECT SUMMARY
Recent advances in understanding the biology of aging have raised the prospect of drug
interventions to promote healthy aging in humans. However, such interventions should have
essentially no toxicity or side effects. In practice, the throughput of drug testing (currently
conducted in animals) is one of the major limitations for identifying interventions to promote
healthy aging. Hence, a challenge is to identify candidate drugs able to induce rejuvenation
and/or healthy aging, with minimal side effects in a high throughput fashion. Here we propose to
take advantage of a novel high content screening approach based on imaging of epigenetic
landscape in single cells. To meet the challenge, we propose to take advantage of a novel
technique we have developed that is rooted in the analysis of epigenome topography at the
single cell level, automated microscopy, and machine learning. “Microscopic Imaging of
Epigenetic Landscapes” (MIEL) captures patterns of nuclear staining of epigenetic marks (e.g.
acetylated and methylated histones) and employs machine learning to accurately distinguish
between such patterns. Pertinent to this application, we have tested whether MIEL approach is
suitable for building a phenotypic cell-based assay for inducers of longevity at the cellular level.
Our preliminary results validated MIEL assay for a high content screening application to identify
novel candidate pro-longevity compounds. In sum, we have developed and validated a high
content cell-based screening assay capable of identifying pro-longevity/healthy aging
compounds based on their effect on epigenetic signature. Our specific Aims are as follows:
Specific Aim 1. Screen for novel inducers of cellular rejuvenation. Specific Aim 2. Validation of
novel inducers of cellular rejuvenation.

## Key facts

- **NIH application ID:** 10043841
- **Project number:** 1R21AG068913-01
- **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:** 2020
- **Award amount:** $292,500
- **Award type:** 1
- **Project period:** 2020-08-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10043841

## Citation

> US National Institutes of Health, RePORTER application 10043841, Phenotypic Screening for Longevity Interventions Using Single-cell Epigenetic Signatures (1R21AG068913-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10043841. Licensed CC0.

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