Ageing is associated with a loss of skeletal muscle mass and function that negatively impacts the independence and quality of life of older individuals. Females demonstrate a distinct pattern of muscle ageing compared to males, potentially due to menopause where endogenous sex hormone production declines. This systematic review aims to investigate the current knowledge about the role of oestrogen in female skeletal muscle ageing. A systematic search of MEDLINE complete, Global Health, Embase, PubMed, SPORTDiscus, and CINHAL was conducted. Studies were considered eligible if they compared a state of oestrogen deficiency (e.g. postmenopausal females) or supplementation (e.g. oestrogen replacement therapy) to normal oestrogen conditions (e.g. premenopausal females or no supplementation). Outcome variables of interest included measures of skeletal muscle mass, function, damage/repair, and energy metabolism. Quality assessment was completed with the relevant Johanna Briggs critical appraisal tool, and data were synthesised in a narrative manner. Thirty-two studies were included in the review. Compared to premenopausal females, postmenopausal females display reduced muscle mass and strength, but the effect of menopause on markers of muscle damage and expression of the genes involved in metabolic signalling pathways remains unclear. Some studies suggest a beneficial effect of oestrogen replacement therapy on muscle size and strength, but evidence is largely conflicting and inconclusive, potentially due to large variations in the reporting and status of exposure and outcomes. The findings from this review points toward a potential negative effect of oestrogen deficiency in ageing skeletal muscle, but further mechanistic evidence is needed to clarify its role.

Hind Limb Ischemia (HLI) is the most severe form of peripheral arterial disease, associated with a substantial reduction of limb blood flow that impairs skeletal muscle homeostasis to promote functional disability. The molecular regulators of HLI-induced muscle perturbations remain poorly defined. This study investigated whether perturbations in the molecular catabolic-autophagy signalling network were linked to temporal remodelling of skeletal muscle in HLI. HLI was induced via hindlimb ischemia (femoral artery ligation) and confirmed by Doppler echocardiography. Experiments were terminated at time points defined as early- (7 days; n=5) or late (28 days; n=5) stage HLI. Ischemic and non-ischemic (contralateral) limb muscles were compared. Ischemic vs. non-ischemic muscles demonstrated overt remodelling at early-HLI but normalised at late-HLI. Early-onset fibre atrophy was associated with excessive autophagy signalling in ischemic muscle: protein expression increased for Beclin-1, LC3 and p62 (p<0.05) but proteasome-dependent markers were reduced (p<0.05). Mitophagy signalling increased in early-stage HLI which aligned with an early and sustained loss of mitochondrial content (p<0.05). Upstream autophagy regulators Sestrins showed divergent responses during early-stage HLI (Sestrin2 increased while Sestrin1 decreased; p<0.05) in parallel to increased AMPK phosphorylation (p<0.05) and lower antioxidant enzyme expression. No changes were found in markers for mTORC1 signalling. These data indicate early-activation of the sestrin-AMPK signalling axis may regulate autophagy to stimulate rapid and overt muscle atrophy in HLI, which is normalised within weeks and accompanied by recovery of muscle mass. A complex interplay between Sestrins to regulate autophagy signalling during early-to-late muscle remodelling in HLI is likely.