The role of telomeres in the ageing of human skin

Abstract

Skin is a self-renewing tissue that is required to go through extensive proliferation throughout the lifespan of an organism. Telomere shortening acts as a mitotic clock that prevents aberrant proliferation such as cancer. A consequence of this protection is cellular senescence and ageing. The telomerase enzyme complex maintains telomere length in germline cells and in cancer cells. Telomerase is also active in certain somatic cells such as those in the epidermis but is almost undetectable in the dermis. Increasing evidence indicates that telomerase plays a significant role in maintenance of skin function and proliferation. Mutations in telomerase component genes in the disease dyskeratosis congenita result in numerous epidermal abnormalities. Studies also indicate that telomerase activity in epidermal stem cells might have roles that go beyond telomere elongation. Telomeres in skin cells may be particularly susceptible to accelerated shortening because of both proliferation and DNA-damaging agents such as reactive oxygen species. Skin might present an accessible tissue for manipulation of telomerase activity and telomere length with the potential of ameliorating skin diseases associated with ageing.

Correlation of telomere length to malignancy potential in non‑melanoma skin cancers

“…Our statistical analyses suggested that the TCR values for epidermal cells located close to each tumor were not associated with patient age, sex, tumor type or sampling site (i.e., chronically or non-chronically exposed to solar radiation). It has been reported previously that TCR values for epidermal cells are reduced with increasing age and chronic sun-exposure (26,27). There are a number of possible explanations for the discrepancy between the present results and the previous ones.…”

Telomerase promoter mutations in cancer: an emerging molecular biomarker?

“…The shortening of telomeres, on the other hand, is believed to provide a barrier for epidermal cell proliferation (i.e. cancer) [11]. Telomerase activity has been reported in cutaneous melanomas, using the TRAP assay, with increasing values from normal skin to benign nevi and to dysplastic nevi and finally to melanoma [29].…”

“…Its activation in the epidermis may be related with the need for cell proliferation and damage repair [11]. The shortening of telomeres, on the other hand, is believed to provide a barrier for epidermal cell proliferation (i.e.…”

Oxydative stress alters nuclear shape through lamins dysregulation

“…In agreement with this model, it has recently been reported that the tail domain of lamin A is a target of oxidative damage, and its irreversible oxidation led to a loss of lamin A function and entry into senescence. 54 Oxidative stress is known to affect telomeres 55 and cause DNA damage; the increase in oxidative stress could therefore also be accountable Figure 1. Interplay between oxidative stress, telomere shortening, and DNA damage for the induction of senescence.…”