Oral Presentation Australasian Society for Dermatological Research Annual Scientific Meeting 2017

Identification of a novel marker for cellular senescence (#14)

Audrey S. Wang 1 , Peh Fern Ong 1 , Alexandre Chojnowski 1 , Aya Wada 1 , Carlos Clavel 1 , Oliver Dreesen 1
  1. Institute of Medical Biology, Singapore, Singapore

Cellular senescence is a critical feature of mammalian cells to suppress tumorigenesis, and a fundamental process that determines cellular ageing in vitro and in vivo. Senescent cells accumulate with age in many tissues, including skin, in pre-neoplastic lesions and at sites of age-related pathologies. As such they limit tissue regeneration and contribute to various age-related pathologies.

Conventionally, senescent cells have been identified by the presence of histologically-detectable senescence-associated β-galactosidase (SA-β-gal) activity. However, SA-β-gal staining is time consuming, works only on very fresh tissues and is not very specific. To circumvent this problem we set out to identify novel senescence-associated biomarkers using the rare genetic accelerated ageing syndrome Hutchinson-Gilford progeria as a model system. This approach was successful as we identified “loss of lamin B1” as a novel biomarker to detect senescent cells. To date, we have validated this marker in human keratinocytes, fibroblasts and melanocytes undergoing replicative senescence, and upon induction of oncogene-induced senescence. In addition, we observed decreased levels of lamin B1 during chronological ageing of human skin.

To investigate whether this marker could be used to quantify the impact of UV exposure on cellular ageing, we first treated different human cell types with increasing doses of UV. We observed an inverse correlation between lamin B1 levels and UV exposure. Secondly, we used a mouse model of chronic low dose UV-exposure to study the role of cellular senescence in UV-induced skin ageing and regeneration in vivo. In conclusion, our findings demonstrate that “loss of lamin B1” is an excellent marker to identify senescent cells – and to quantify the impact of environmental factors on cellular ageing in vitro and in vivo.