# Sepsis-induced myopathy in aging: influence of disuse on skeletal muscle regeneration

> **NIH NIH R21** · FLORIDA STATE UNIVERSITY · 2021 · $231,000

## Abstract

PROJECT SUMMARY
Sepsis is a condition of life-threatening organ dysfunction caused by a dysregulated host response to infection
and carries a high risk of mortality, especially among older adults. Despite decreasing in-hospital mortality due
to early recognition and aggressive intensive care unit (ICU) management, a rapidly growing number of “sepsis
survivors” experience persistent and severe skeletal muscle weakness and atrophy (i.e. sepsis-induced
myopathy). These patients often experience prolonged periods of bed rest, which possibly worsens the
myopathy. For unknown reasons, the skeletal muscles of these patients never return to their pre-septic functional
condition. Healthy skeletal muscles possess a great regenerative capacity that is regulated by a populations of
resident cells known as satellite cells (SCs). SCs are localized between the muscle membrane and the basal
lamina and are exposed to other cells and their secretory products, including chemokines, in the so called SC
niche. We have shown that SCs lose their ability to regenerate muscle fibers in sepsis, a response that is known
to occur in the process of aging. We have also shown that sepsis induces epigenetic changes in the SCs that
are associated with the loss of function. Our preliminary observations identified circulatory chemokines known
to be elevated in sepsis and aging. Exposure of healthy SCs to this septic serum resulted in a loss of myogenic
capacity. The mechanisms by which the combination of sepsis, aging and skeletal muscle disuse contributes to
the persistent myopathy and failure to regenerate in older adults remain unknown. We will test the overarching
hypothesis that when faced with severe immunological stress of sepsis, on top of aging and disuse, these
critically important resident cells are unable to facilitate complete recovery of muscle function. We will test this
hypothesis with two specific aims. Drawing largely from clinical observations and our unpublished preliminary
data we will combine a classic model of sepsis with hindlimb suspension followed by reloading to 1) test the
hypothesis that disuse aggravates skeletal muscle dysfunction and hampers repair via satellite cell dysfunction
in aged septic hosts; and 2) determine the epigenetic signatures of satellite cells from aged septic hosts and the
role of chemokine receptors on these signatures. We anticipate that this study will result in a novel pre-clinical
model to study sepsis-induced myopathy in aging. The identification of epigenetic signatures in SCs of aged
septic hosts will reveal therapeutic targets for epigenetic modifiers to attenuate the myopathy. In due course, this
can benefit a substantial number of older adults who have worsened muscle function after admission to the ICU
and may be applicable for older patients who are exposed to other types of infections, such as those affected by
the current COVID-19 pandemic.

## Key facts

- **NIH application ID:** 10194969
- **Project number:** 1R21AG072011-01
- **Recipient organization:** FLORIDA STATE UNIVERSITY
- **Principal Investigator:** Orlando Laitano
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $231,000
- **Award type:** 1
- **Project period:** 2021-06-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10194969

## Citation

> US National Institutes of Health, RePORTER application 10194969, Sepsis-induced myopathy in aging: influence of disuse on skeletal muscle regeneration (1R21AG072011-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10194969. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*