Ten-day bed rest in older adults increased mitochondrial ROS emission and reduced mitochondrial mass in skeletal muscle despite preserved respiratory function, indicating that elevated ROS production occurs upstream of respiratory dysfunction and is potentially linked to impaired antioxidant defence and ROS clearance.
Key Findings
Results
Ten days of bed rest increased mitochondrial reactive oxygen species (ROS) emission under non-phosphorylating conditions in older adults.
Ten healthy older men aged 65+ years underwent 10 days of bed rest.
H2O2 emission was measured as a proxy for mitochondrial ROS production.
The increase in ROS emission occurred specifically under non-phosphorylating (state 4) conditions.
Transcriptomic analysis revealed dysregulation of antioxidant and oxidoreductase genes, indicating reduced capacity for ROS clearance.
The authors interpret elevated ROS production as occurring upstream of respiratory dysfunction.
Results
Oxidative phosphorylation (OXPHOS) capacity was preserved after 10 days of bed rest in older adults.
Mitochondrial respiration was assessed using high-resolution respirometry on skeletal muscle biopsies collected before and after bed rest.
Respiratory capacity was preserved under both submaximal and maximal stimulation.
When normalized to mitochondrial content (citrate synthase activity), respiratory capacity increased, suggesting improved intrinsic efficiency.
Mitochondrial respiratory complex and supercomplex protein abundance were unchanged after bed rest.
Results
Mitochondrial mass was reduced after 10 days of bed rest, as shown by decreased mitochondrial volume density.
Mitochondrial volume density was assessed morphologically using electron microscopy.
Reduced mitochondrial volume density was observed post-bed rest.
Citrate synthase activity was used as a biochemical marker of mitochondrial content.
Transcriptomic alterations in the mitophagy pathway suggest a potential role of altered mitochondrial degradation in the reduction of mitochondrial mass.
Results
Reduced dynamin-like protein 1 (DRP1) phosphorylation at serine 637 was observed after bed rest, while other mitochondrial fission and fusion protein levels remained unchanged.
DRP1 phosphorylation at serine 637 was specifically reduced post-bed rest.
Other mitochondrial fission and fusion protein levels were not significantly altered.
Mitochondrial morphology remained unaltered despite changes in DRP1 phosphorylation.
Mitochondrial protein expression was assessed from skeletal muscle biopsies collected before and after bed rest.
Results
Transcriptomic analysis revealed more than 3000 differentially expressed genes after 10-day bed rest, characterized by downregulation of oxidative phosphorylation genes alongside altered mitophagy, antioxidant, and oxidoreductase pathways.
More than 3000 differentially expressed genes were identified between pre- and post-bed rest conditions.
Oxidative phosphorylation genes were downregulated at the transcriptomic level despite preserved OXPHOS protein abundance and function.
Alterations were observed in mitophagy, antioxidant, and oxidoreductase pathway gene expression.
Transcriptomic profiling was conducted on skeletal muscle biopsies from 10 older men.
The dysregulation of antioxidant genes was interpreted as indicating a reduced capacity for ROS clearance.
Discussion
The study authors conclude that functional impairments during short-term inactivity in older adults are likely driven by cardiovascular and microvascular factors rather than mitochondrial respiration itself.
The findings are interpreted as representing a transient compensatory response of ageing mitochondria to short-term disuse.
Preserved and even intrinsically improved mitochondrial respiratory capacity after bed rest supports the conclusion that in vivo exercise intolerance is not primarily of mitochondrial origin.
The authors suggest that preserving redox balance during inactivity may be a key strategy to maintain muscle health and functional independence in ageing populations.
The study examined 10 healthy older men (65+ years) undergoing 10 days of bed rest.
What This Means
This research suggests that just 10 days of bed rest causes meaningful changes in the muscle cells of older adults (age 65+), even over a short period of inactivity. The most notable change was an increase in the production of harmful reactive oxygen species (ROS, sometimes called 'free radicals') by mitochondria — the energy-producing structures inside cells — along with a reduction in the total amount of mitochondria present in muscle tissue. Genes involved in the body's natural antioxidant defenses were also disrupted, suggesting the muscles become less able to neutralize the increased ROS. Surprisingly, despite these changes, the mitochondria that remained were still able to produce energy normally, and when energy production was measured relative to the amount of mitochondria present, it actually appeared more efficient than before bed rest.
This research suggests that in older adults, short periods of physical inactivity trigger oxidative stress (an imbalance between harmful free radicals and the body's ability to neutralize them) before any actual breakdown in mitochondrial energy production occurs. This is an important distinction because it implies that when older people become less fit or fatigued after a period of inactivity or illness, the problem may not be in the mitochondria themselves, but rather in factors such as blood flow and oxygen delivery to the muscles, or in the increased burden of oxidative stress.
Practically, these findings point to redox balance — keeping oxidative stress in check — as a potentially important target for preserving muscle health in older adults who experience periods of inactivity, such as during hospitalization or illness-related bed rest. This could inform future strategies around antioxidant interventions or early mobilization protocols for older patients, though the study was small (10 men) and further research would be needed to confirm and extend these findings.
Motanova E, Zuccarelli L, Lysenko E, Amoretti S, Pirazzini M, Rossetto O, et al.. (2026). Preserved mitochondrial respiration in presence of oxidative stress and reduced mitochondrial mass after 10-day bed rest in older adults.. The Journal of physiology. https://doi.org/10.1113/JP291588