Author links open overlay panelHolly N.WilkinsonMatthew J.Hardman
•Ageing induces morphological and biomechanical changes in the skin.
•Extracellular matrix composition modulates the skin’s biomechanical properties.
•Estrogen deficiency accelerates age-induced extracellular matrix deterioration.
•Exogenous 17β-estradiol reverses age-related degradation of the extracellular matrix.
The skin is the body’s primary defence against the external environment, preventing infection and desiccation. Therefore, alterations to skin homeostasis, for example with skin ageing, increase susceptibility to skin disease and injury. Skin biological ageing is uniquely influenced by a combination of intrinsic and extrinsic (primarily photoageing) factors, with differential effects on skin structure and function. Interestingly, skin architecture rapidly changes following the menopause, as a direct result of reduced circulating 17β-estradiol. The traditional clinical benefit of estrogens are supported by recent experimental data, where 17β-estradiol supplementation prevents age-related decline in the skin’s structural and mechanical properties. However, the off-target effects of 17β-estradiol continue to challenge therapeutic application. Here we discuss how ageing alters the physiological and structural properties of the dermal extracellular matrix, and explore how estrogen receptor-targeted therapies may restore the mechanical defects associated with skin ageing.