The Pigmentary System in Photoaged Skin

The aging process, both intrinsic and extrinsic, produces a variety of responses by melanocytes. These processes are both inhibitory and stimulatory. It has been established that the number of dopa-positive melanocytes decreases with age by approximately 10–20% per decade [52, 53]. The decrease in melanocyte number occurs in both sun-exposed and sunprotected areas of the skin. This, along with a loss in the skin’s vasculature, would explain the pale appearance of intrinsically aged skin. However, with long-term sun exposure, the density of melanocytes increases and is approximately two-fold higher than in sun-protected skin [25]. The molecular events underlying the action of UV radiation on melanocytes are largely unknown [38]. In vitro,multiple exposures to UV radiation inhibit melanocyte growth [54, 55]. Melanocytes irradiated with UVB are known to be blocked in the G1 phase of replication. However, the situation in vivo is different. After UV exposure, melanocyte density increases, as demonstrated by Quevedo. In his study, the number of melanocytes increased when buttock skin was irradiated with UV light [52]. Melanocytes are thus influenced by a number of factors, some of which increase their number and production of melanin. These factors include cytokines and growth factors, which are stimulated with UV exposure and include interleukins 1, 6, and 8, TNF-alpha, TGFbeta, BFGF, growth factor, endothelin derivatives, and nerve growth factor [56, 57, 58, 59]. These cytokines and growth factors have a direct effect on melanocyte proliferation and survival and play a role in the pathogenesis of pigmentary changes of photoaged skin [38].Additionally, inflammatory mediators formed during UV exposure, such as leukotriene C1, stimulate growth of melanocytes and modifications in the normal melanocyte phenotype [60].

Histological features of the pigmentary change associated with photoaging, including mottled hyperpigmentation, ephelides, solar lentigines, seborrheic keratoses, and guttate hypopigmentation, have been investigated. Areas of mottled hyperpigmentation correlate with an irregular distribution of melanocytes along the basement membrane. Melanocytes display increased dopa-positivity, and there is a heterogeneous distribution of melanosomes within the keratinocytes [39].Ephelides display hyperpigmentation of the basal cell layer without elongation of the rete ridges. It has been demonstrated by light and electron microscopy that ephelides have fewer melanocytes than adjacent, paler skin [38]. However, the melanocytes of ephelides,which are large and strongly dopapositive, produce eumelanosomes and hence darker eumelanin whereas in adjacent, paler skin, melanocytes often produce pheomelanosomes and lighter pheomelanin [39].


Solar lentigines, a hallmark of photoaged skin, are characterized histologically by an increase in melanocytes and melanin synthesis. There is hyperpigmentation of the basal cell layer with elongation of the rete ridges. The rete ridges are club shaped or have bud-like extensions [61]. There is an overall increase in the number of melanocytes. Electron microscopic studies demonstrate an increase in the activity of melanocytes, as well. The melanocytes are normal with no cytological atypia, although the nuclei are irregularly shaped [38]. Large numbers of melanosomes are observed in keratinocytes as well as in the stratum corneum. Braun-Falco suggested that in the lentigo, there may be a possible abnormality in the lysosomal degradation of pigment granules within the epidermal keratinocyte [62]. A reticulated black solar lentigo, a black macule with an irregular outline, histologically displays lentiginous hyperplasia with elongation of the rete ridges and hyperpigmentation of the basal layer with skip areas [43]. Melanocytes are not especially numerous, but they show thicker and more prominent dendrites.

Pigmented seborrheic keratoses, another lesion observed in photoaged skin, has variable amounts of melanin pigmentation. Melanocytes are present in the basal layers of seborrheic keratoses and in suprabasal locations.Melanosomes are transferred to epidermal keratinocytes and are found predominantly in the keratosis. Guttate hypomelanosis of aging is characterized histologically with flattening of the dermal- epidermal junction and a 10–55% reduction in the number of dopa-positive keratinocytes [37]. Ultrastructurally, the melanosomal content of the epidermal keratinocytes is variable with some containing numerous melanosomes and others containing only immature melanosomes.