Frailty and COPD: a bidirectional relationship in the context of systemic and accelerated ageing

Chronic obstructive pulmonary disease (COPD) is increasingly recognised as a systemic disorder that extends beyond the lungs, representing a clinical model of accelerated ageing. Frailty, a multidimensional syndrome characterised by reduced physiological reserve and increased vulnerability to stressors, is highly prevalent among individuals with COPD and contributes to adverse outcomes. Both conditions share common biological mechanisms, including chronic inflammation, oxidative stress, endocrine dysregulation, mitochondrial dysfunction and skeletal muscle atrophy. Exercise acts as a physiological stressor that elicits hormetic responses, triggering favourable molecular adaptations such as enhanced mitochondrial biogenesis, improved redox balance and the upregulation of antioxidant and cellular repair pathways. These adaptations translate into improved muscle function, metabolic efficiency and immune homeostasis, thereby counteracting the catabolic processes that underlie both frailty and COPD progression. Scientific evidence supports the role of combined aerobic, resistance and balance training as the most effective approach to improving functional status and quality of life in frail individuals with COPD. Frailty in COPD represents a potentially reversible state of systemic vulnerability rooted in accelerated biological ageing. Exercise thus constitutes a powerful, multi-target intervention capable of reprogramming molecular ageing pathways and promoting resilience across organ systems. Integrating exercise physiology with the principles of geroscience offers a promising framework for personalised rehabilitation strategies aimed at extending health span in patients with COPD. This narrative review summarises current evidence on the biological and clinical interplay between COPD, frailty and exercise, exploring how physical activity exerts systemic anti-ageing effects through modulation of inflammation, oxidative stress, mitochondrial and myokine signalling, ultimately restoring physiological resilience.