Mitochondrial respiratory chain deficiency is associated with an impaired skeletal muscle regenerative response and fibrosis in older men with HIV

Despite suppressive anti-retroviral therapy (ART), some older people with HIV show adverse ageing phenotypes, and the underlying mechanisms remain incompletely understood. We recruited 30 men with HIV aged ≥ 50 years and 15 well-matched men without HIV and performed histological analyses on skeletal muscle biopsies and plasma biomarker measurement, in combination with clinical and functional assessments. Men with HIV showed higher frequencies of frailty, pre-frailty, sarcopenia, and pre-sarcopenia when compared to men without HIV. When assessing skeletal muscle, men with HIV had decreased mitochondrial complex I and IV protein abundance and myofibre regeneration, whilst fibrosis was increased, and plasma TNFα and MCP-4 levels were elevated. Spearman correlation analyses suggested that inflammation and mitochondrial respiratory chain deficiency may result in a damage response in skeletal muscle with resolution by fibrosis rather than regeneration. These findings thus provide plausible rationales for adverse ageing phenotypes in older men with HIV, including frailty and sarcopenia.