Exercise Ageing Research: Mitoquinol and Redox Responses in Older Adults
Written by Tyla Cornish (BNatMed), Naturopath. Reviewed by Dr. Siobhan Mitchell (PhD), Neuroscience.
Ageing is associated with impaired redox signalling in skeletal muscle, which may contribute to attenuated exercise adaptation in older adults. Mitochondrial ROS production increases with age, and it has been proposed that this excess oxidative burden may disrupt the signalling cascades through which exercise drives adaptation. This study examined whether Mitoquinol restores exercise-induced redox responses in older adults by reducing mitochondrial ROS.
Research Summary
Evidence type: Randomised, double-blind, placebo-controlled trial
Claim strength: Causal, negative/mixed
Population: 22 older adults (65–80 years)
Intervention: Mitoquinol (MitoQ) 20 mg/day vs placebo (12 week period)
Primary outcomes: Redox signalling, mitochondrial function, gene expression
Observed outcome: Reduced mitochondrial ROS production; no effect on exercise-induced signalling or gene expression
Causality: Not supported for functional adaptation
Primary source: Redox Biology
What you’ll learn
Whether reducing mitochondrial oxidative stress can restore exercise adaptation in older adults
How ageing alters redox signalling and muscle responsiveness to exercise
Why lowering ROS does not necessarily restore downstream adaptive signalling pathways
The distinction between correcting oxidative stress and restoring cellular signalling capacity
What the Study Observed
Participants received Mitoquinol or placebo for 12 weeks alongside exercise, with redox signalling, mitochondrial function, and gene expression assessed before and after the intervention. While Mitoquinol successfully reduced mitochondrial ROS production, it did not restore exercise-induced signalling responses or alter gene expression patterns associated with adaptation. Mitochondrial function was also unchanged.
What Are the Implications for Ageing and Exercise?
The finding that Mitoquinol reduced mitochondrial ROS but failed to restore downstream signalling is one of the most mechanistically informative results in this literature. It suggests that the impaired exercise-induced signalling observed in older skeletal muscle is not simply a consequence of excess ROS disrupting redox-sensitive pathways — if it were, reducing ROS should have restored the signal. Instead, this dissociation points to a more fundamental disruption in the signalling architecture of aged muscle: changes in sensor sensitivity, downstream kinase activity, transcription factor responsiveness, or the capacity of aged cells to transduce a redox signal into a gene expression response regardless of ROS levels.
In other words, the problem in older skeletal muscle may not be that there is too much oxidative noise drowning out the adaptive signal, but rather that the signal transduction machinery itself is less responsive — a distinction with significant implications for how antioxidant-based strategies should be designed and targeted in ageing research.
The small sample size (n=22) also limits confidence in the null findings related to gene expression and mitochondrial function, where effect sizes may be modest and individual variability high in an older cohort.
Mitochondrial-targeted antioxidants may still have a role in lowering excessive oxidative burden, but restoring adaptive capacity is likely to depend on re-sensitising downstream signalling pathways or enhancing mitochondrial biogenesis and metabolic flexibility through complementary interventions. In practice, this supports a multimodal approach that combines targeted supplementation with exercise modalities known to stimulate PGC‑1α signalling, as well as interventions that support cellular energetics and signalling fidelity. It also reinforces the importance of setting realistic expectations: reducing oxidative stress does not necessarily translate into improved functional adaptation in older populations, particularly over short intervention periods.
Critical Considerations for Future Research
Future studies should go beyond measuring ROS reduction as a proxy for therapeutic success and instead map the downstream signalling cascade in detail: which kinases, transcription factors, and gene networks fail to respond even when oxidative burden is reduced. This would help identify where in the signalling chain ageing exerts its most disruptive effects, and whether combining Mitoquinol with interventions targeting those downstream nodes — such as NAD+ precursors that restore sirtuin activity, or exercise modalities that specifically drive PGC-1α — could produce additive benefit. Larger sample sizes with careful stratification by baseline fitness and mitochondrial function are also warranted, as the heterogeneity of the 65–80 year age range may mask subgroups in whom Mitoquinol does produce functional effects.
Read the full paper:Mitoquinol supplementation does not impact redox responses to acute exercise in skeletal muscle of older individuals
DOI: 10.1016/j.redox.2025.103927
