Related Experiment Video
Updated: Sep 3, 2025
08:55
The Colon-26 Carcinoma Tumor-bearing Mouse as a Model for the Study of Cancer Cachexia
Published on: November 30, 2016
16.5K
PGC1α overexpression preserves muscle mass and function in cisplatin-induced cachexia
Joshua R Huot1,2, Fabrizio Pin2, Rohit Chatterjee1
1Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA.
Journal of Cachexia, Sarcopenia and Muscle
|July 29, 2022
Summary
Chemotherapy causes muscle wasting, but overexpressing peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC1α) can protect against these effects, particularly in older animals. Mitochondria-targeted strategies show promise in preventing chemotherapy-induced muscle problems.
Area of Science:
- Mitochondrial biology and biogenesis
- Skeletal muscle physiology
- Chemotherapy-induced side effects
Background:
- Chemotherapy can induce a cachexia-like state, characterized by skeletal muscle wasting, weakness, and mitochondrial dysfunction.
- Peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC1α), a key regulator of mitochondrial biogenesis, is often reduced in cachectic muscle.
- The role of PGC1α in mitigating chemotherapy-induced muscle damage, especially in aged individuals, requires further investigation.
Purpose of the Study:
- To investigate whether PGC1α overexpression can counteract the skeletal muscle-related side effects of cisplatin chemotherapy.
- To compare the effects of cisplatin on muscle mass, function, and mitochondrial health in young versus aged mice.
- To evaluate the protective potential of PGC1α in combating chemotherapy-induced neuromuscular dysfunction.
Main Methods:
- Utilized young and old wild-type (WT) and PGC1α transgenic (Tg) male and female mice.
- Administered cisplatin (C) or saline to mice for two weeks.
- Assessed muscle mass, muscle force, motor unit number estimation (MUNE), and mitochondrial protein expression.
Main Results:
- Cisplatin reduced muscle mass, force, and MUNE in young WT mice; these effects were more pronounced in aged WT mice.
- PGC1α overexpression offered mild protection against muscle mass loss in young Tg mice but preserved neuromuscular function.
- In aged mice, PGC1α overexpression significantly preserved muscle mass, force, and MUNE, and prevented muscle wasting and weakness.
Conclusions:
- Aged animals exhibit heightened susceptibility to cisplatin-induced muscle wasting and weakness.
- PGC1α overexpression effectively combats cisplatin-induced neuromuscular dysfunction, particularly in older animals.
- Mitochondria-targeted strategies, such as PGC1α modulation, hold potential for preventing chemotherapy-related muscle atrophy and weakness.
