# Sen-Survivors: An open-label intervention trial for frailty and senescence

> **NIH NIH U01** · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · 2020 · $2,277,711

## Abstract

ABSTRACT
Over 80% of children diagnosed with cancer will survive at least ten years after diagnosis. However, by age 50
years each survivor, on average experiences >4 severe or life-threatening (CTCAE grades 3-4) health chronic
conditions (rates typically seen in persons decades older) raising concern for early onset of physiologic frailty.
Frailty is a loss of physiologic capacity that interferes with normal function, most commonly described in older
adults and characterized (Fried Criteria) by three or more of: 1) low lean muscle mass, 2) reduced strength, 3)
slow walking speed, 4) low energy expenditure, and 5) fatigue. In the general population frailty is seen in the
elderly. However, at a median age of only 33 years (range 18-50), 8% of survivors are frail, an additional 22.2%
meet the definition of pre-frail (two of five criteria), rates similar to adults >65 years of age. Cellular senescence,
a quiescent state representing the loss of a cell's ability to replicate or grow, is an important and established
mechanism in the aging process. Senescence is strongly associated with frailty and aging biomarkers in the
elderly population. There is now evidence that p16INK4A is elevated in survivors treated with chemotherapy and
radiotherapy, and the magnitude of elevation is associated with measures of frailty. Thus, cellular senescence
may provide a targetable pathway to improve measures of aging. Agents such as Dasatinib and flavonoids
(Quercetin; Fisetin, available as nutritional supplements) interfere with this pathway and thus are “senolytic”. Six
clinical trials of efficacy are now underway in chronic disease states associated with senescence (e.g. idiopathic
pulmonary fibrosis) and frail populations, including adult bone marrow transplant recipients demonstrating initial
evidence for safety and tolerability and that senolytics alleviate physical dysfunction. However, to date, no trial
has evaluated senolytic agents in adult survivors of childhood cancer. In order to address this gap in knowledge,
we utilize the well-phenotyped population of the St. Jude Life Cohort Study to propose a two arm, randomized,
open-label pilot intervention trial in frail survivors (Fried Criteria) of childhood cancer who have diminished
walking speed and increased cellular senescence (increased p16INK4a mRNA expression level in peripheral blood
T lymphocytes). We aim to test the efficacy of two senolytic regimens: 1) combination of Dasatinib plus
Quercetin, and 2) Fisetin alone, to reduce senescent cell abundance in blood and improve walking speed (1°
Aim). Secondary endpoints include: additional measures of frailty beyond walking speed (i.e. additional Fried
Frailty Criteria), markers of inflammation, insulin resistance, bone resorption and cognitive function. We
hypothesize that senolytic therapy will reduce biological markers and clinical measures of aging. Additionally,
we will test the safety and tolerability of these senolytic therapies. If successful, this s...

## Key facts

- **NIH application ID:** 9890475
- **Project number:** 1U01CA246510-01
- **Recipient organization:** ST. JUDE CHILDREN'S RESEARCH HOSPITAL
- **Principal Investigator:** Gregory Armstrong
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $2,277,711
- **Award type:** 1
- **Project period:** 2020-09-01 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9890475

## Citation

> US National Institutes of Health, RePORTER application 9890475, Sen-Survivors: An open-label intervention trial for frailty and senescence (1U01CA246510-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9890475. Licensed CC0.

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