# Chronic muscle weakness in sepsis survivors

> **NIH NIH R01** · UNIVERSITY OF KENTUCKY · 2020 · $290,700

## Abstract

ABSTRACT
The objective of this project is to identify sub-cellular and molecular mechanisms of skeletal muscle
dysfunction that are responsible for chronic weakness in sepsis survivors. Using the knowledge obtained, this
project will elucidate potential therapeutic interventions targeting post-sepsis chronic muscle weakness. Over 1
million sepsis survivors are now discharged from the hospital every year, and a majority of these survivors
report reduced quality of life due to considerable muscle weakness lasting for years after hospital discharge.
However, the lack of an appropriate animal model has been a critical barrier to identifying the changes which
persist long after recovery from sepsis. We recently developed a new mouse model that has enabled us to
evaluate long-term muscle quality and function in severe sepsis survivors. Our preliminary studies demonstrate
that sepsis-surviving mice exhibit significant skeletal muscle weakness, even after bacterial infection and
inflammation are resolved and muscle mass is recovered, giving us the unique opportunity to evaluate
molecular mechanisms of muscle weakness beyond the muscle wasting phenotype. Skeletal muscles from
these sepsis-surviving mice also show histological abnormalities, significant nitro-oxidative damage, and
profound structural and functional defects in mitochondria. These preliminary results support our central
hypothesis that sepsis-induced oxidative damage causes mitochondrial dysfunction and sarcomeric protein
damage, both of which remain long after sepsis recovery, and these are the major contributors to the sustained
skeletal muscle weakness in sepsis survivors. Specific Aims to test the hypothesis are: (1) To determine
mitochondrial damage and dysfunction in sepsis-surviving mice; (2) To investigate sarcomeric protein damage
and its causal mechanisms in sepsis-surviving mice; and (3) To formulate therapeutic strategies to ameliorate
post-sepsis chronic muscle weakness.

## Key facts

- **NIH application ID:** 9997972
- **Project number:** 5R01GM126181-04
- **Recipient organization:** UNIVERSITY OF KENTUCKY
- **Principal Investigator:** Hiroshi Saito
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $290,700
- **Award type:** 5
- **Project period:** 2017-09-15 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9997972

## Citation

> US National Institutes of Health, RePORTER application 9997972, Chronic muscle weakness in sepsis survivors (5R01GM126181-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9997972. Licensed CC0.

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