OBJECTIVE: Few histological studies have directly examined age-related changes within the lips, although non-invasive investigations of such changes are increasing. Therefore, this study aimed to provide histological and molecular data on age-dependent alterations in the vermilion. METHODS: Upper vermilion specimens from 15 female Caucasian cadavers (age range, 27-78 years) were investigated histologically or immunohistochemically. RESULTS: Histologically, age-dependent decreases in areas occupied by hyaluronan and collagenous fibres in the dermis of upper vermilion were demonstrated. Elastic fibre content varied widely between individuals. The area occupied by muscle fibres in the orbicularis oris muscle region within the vermilion also correlated negatively with age. Immunohistochemically, signals of four proteins were attenuated in vermilion from older individuals compared with young individuals: procollagen type I, hyaluronan synthase (HAS)1, myosin heavy chain (MYH)2 (a component of fast-twitch oxidative muscle fibres) and MYH7 (a component of slow-twitch muscle fibres). In contrast, signals of cell migration inducing hyaluronidase 1 (CEMIP) were intensified in vermilion from older individuals. No marked differences between young and older individuals were seen in procollagen type III, HAS2, HAS3, hyaluronidase (HYAL)1, HYAL2, MYH1 or MYH4. CONCLUSION: Age-dependent decreases of hyaluronan in the dermis of vermilion were prominent, possibly due to both the decrease in synthesis (HAS1) and the increase in degradation (CEMIP). Furthermore, age-dependent decreases in collagenous fibres and two types of muscle fibre in the vermilion were also identified histologically. Type I collagen, MYH2 and MYH7 appear to represent the molecules responsible for these respective decrements.