Purpose of Review <p>Bone matrix is a multiscale composite material mainly composed of collagen, crystalline apatite mineral, water, and a small amount of non-collagenous proteins. Nested within bone matrix, mechanosensitive osteocytes orchestrate bone adaptation to mechanical loading, which is affected by the ultrastructural composition and mechanical properties of the osteocyte-surrounding bone matrix. In this review, we shed light on the impact of ageing-related modifications in ultrastructural composition of bone matrix on the mechanosensitivity of osteocytes.</p> Recent Findings <p>Ageing modulates the ultrastructural composition of bone matrix, such as collagen cross-links, mineral crystal size, microcracks, content of bound water, content and phosphorylation of non-collagenous proteins, and degree of mineralization. These ageing-related modifications alter the mechanical properties of bone matrix, and the biological function of bone, i.e. altered mechanical properties lead to changes in mechanical loading-induced fluid shear stress experienced by osteocytes, which affect osteocyte mechanosensitivity.</p> Summary <p>A better understanding of the role of osteocyte mechanosensitivity in bone adaptation to mechanical loading during ageing is crucial. This review highlights the ageing-related changes in the ultrastructural composition and mechanical properties of bone matrix, that might affect the mechanosensitivity of osteocytes. By linking ageing-related changes in the bone matrix to alterations in osteocyte mechanosensitivity, it is assumed that ageing-modulated bone matrix affects bone adaptation to mechanical loading orchestrated by osteocytes. A comprehensive understanding of how age-related changes in bone matrix composition influence osteocyte mechanosensitivity is crucial for explaining the fragility of ageing bone, as osteocytes are the most abundant and mechanosensitive cells in bone tissue.</p>