# Integrated Healthspan Phenotyping

> **NIH NIH P01** · MAYO CLINIC ROCHESTER · 2020 · $282,076

## Abstract

CORE C: SUMMARY Pignolo
The overall objective of Core C: Integrated Healthspan Phenotyping Core (IHPC) is to characterize novel
animal models of senescent cell clearance by a variety of functional assessments across multiple domains.
The IHPC will characterize two common models of senescent cell clearance in vivo, and integrate the use of
these models across all four projects. One model will use the ATTAC cassette, which is a caspase-8/Fkbp
fusion protein that causes cell death in the presence of the drug AP20187. In this model, a p16-INK-ATTAC
transgenic rat model, the ATTAC cassette is driven by the p16 promoter. The second model is a physiological
aging model treated with senotherapeutic drugs identified by Core B: Drug Discovery & Development. We
anticipate that three or more potential senolytic (i.e., compounds that kill senescent cells)/senomorphic (i.e.,
compounds that inhibit the senescence-associated secretory phenotype [SASP]) drugs will be evaluated for
effects on normal (physiologic) aging in mice. The lead senotherapeutic agent identified in mice will also be
evaluated for healthspan benefits in the p16-INK-ATTAC transgenic rat model. These common animal models
will be bred, maintained, and characterized for health span measures by the IHPC. By identifying animal
models with extended health (e.g., models that reduce senescent cell burden) we will determine strategies
capable of compressing morbidity as well as enhancing and extending health span in humans. The following
functional domains related to Projects 1-4 will be assessed to characterize the healthspan across animal
models: (i) metabolic homeostasis, body composition and energetics, (ii) skeletal integrity, (iii) cardiovascular
function, (iv) muscle performance, and (v) immunologic/inflammatory status. A health index checklist will be
utilized as a global assessment of functional status. These outcomes of healthspan have been selected for
their stand-alone importance, clinical relevance, and established relationships with frailty, disability,
institutionalization, and longevity in older persons. The ability to determine these outcomes in rodents will
greatly enhance our ability to translate the basic biology of aging into clinical application-- the overarching goal
of the Program Project. The IHPC will interact closely with Core D: Geroscience Pathology & Cellular Histology
to facilitate examination of tissue samples from these models for a wide range of standard and innovative
histological and pathophysiological analyses. The IHPC will also interact closely with Core A: Administrative
and Biostatistics Core, to collect, curate, and manage data related to tissue sample collection, functional
parameters, and histopathological findings as well as to oversee the distribution of animal models to Project
Leads and other, non-PPG investigators, upon request.

## Key facts

- **NIH application ID:** 9938397
- **Project number:** 5P01AG062413-02
- **Recipient organization:** MAYO CLINIC ROCHESTER
- **Principal Investigator:** ROBERT JOHN PIGNOLO
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $282,076
- **Award type:** 5
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9938397

## Citation

> US National Institutes of Health, RePORTER application 9938397, Integrated Healthspan Phenotyping (5P01AG062413-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9938397. Licensed CC0.

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