Due to its association with adverse outcomes, the simultaneous concurrence of sarcopenia and osteoporosis, a condition termed osteosarcopenia, has raised attention and concern. Fat infiltration contributes to age-related bone and muscle decline. This effect could be explained by fat-secreted factors, which could be locally secreted in the muscle and bone milieu thus affecting cell-cell interactions, and cell function and survival. However, the specific fat-secreted factors that simultaneously affect those tissues remain unknown. Using new targeted-lipidomic approach via liquid chromatography with tandem mass spectrometry, we comprehensively quantified fat composition (lipid metabolites [LMs]) in gastrocnemius, serum, and bone marrow flushes from tibia and femur obtained from young (6W) and old (24W) C57BL6 mice. Compared to young mice, all tissues in older mice showed significantly higher levels of arachidonic acid (AA) (p=0.042) and AA-derived eicosanoids, PGs2α (p=0.036), PGsα(p=0.021), which are known to affect muscle and bone function. Moreover, Lipoxin B4, another AA product and an enhancer of bone turnover and negative regulator for muscle, showed significantly lower values in older mice compared to young mice in both genders (p= 0.0092). Furthermore, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) autoxidation products (20-HDoHE, 11-HDoHE, 7-HDoHE and 4-HDoHE), an omega-3 fatty acids that negatively regulate bone and muscle health were significantly higher in older mice (p=0.003, p=0.020, p=0.025, p=0.045 respectively). Additionally, γ-aminobutyric acid (GABA) and β-aminoisobutyric acid (BAIBA), which they are muscle-derived osteocyte survival factors, were significantly lower with older mice and higher in females than males (p<0.05). In conclusion, elucidation of those LMs that are present in both ageing muscle and bone could provide valuable evidence on the role of fat infiltration in osteosarcopenia. These results suggest that LMs could play a role in modulating musculoskeletal function during aging, which might relate to sarcopenia and osteoporosis, and could become therapeutic targets in the future.