Can I convice you to wear sunscreen?

Aging is a physiological process in which a decline in tissue function appears. Skin aging, which is the main study field of our lab, can be divided between intrinsic and extrinsic aging. Intrinsic aging is the one that occurs due to passage of time. Extrinsic aging is the one that is caused by exposure to external harmful stimuli such as UV irradiation or pollution.

A picture is worth a thousand words. In the next image we can observe the face of a man who had driven a truck for 28 years, receiving the sunlight, and thus UV irradiation, on his left side. The left side of his face is a good example of extrinsic aging while his right side is a consequence of the passage of time, reflecting the intrinsic aging of this 69-year-old man.

The process of aging is characterized by several hallmarks, among them, the increase in the number of senescent cells, impaired proteostasis and mitochondrial dysfunctions are the main topics of our interest.

Senescence is a process in which the cells stop proliferating since their cell cycle is arrested. However, senescent cells remain metabolically active and contribute to the decline of skin function. This contribution is mainly due to the synthesis and secretion of a wide set of immunomodulatory and inflammatory factors known as SASP (Senescence Associated Secretory Phenotype) which support the increased inflammation observed during aging.

Protein homeostasis, also called proteostasis refers to the balance between protein synthesis, folding and degradation. During the process of aging, reactive oxygen species (ROS) are produced, and cellular proteins and consequently proteostasis are damaged. For this reason, cellular mechanisms for eliminating these damaged macromolecules, like proteasomal elimination or autophagy, must be activated. During aging these mechanisms are also impaired leading to the accumulation of undegraded material. Dysfunctional proteostasis is of special interest because it contributes to senescence and aging.

Mitochondrial dysfunctions are also observed during aging, contributing to the ROS generation, which, in turn, damages cellular molecules and organelles. Additionally, mitochondrial impairment is linked to bioenergetics, metabolic alterations and SASP molecules production.

Our research field is focused on mechanisms of extrinsic aging. As we have seen sunlight can be harmful for the skin, that is why one of our main models include a UVB irradiation model in which dermal fibroblasts are exposed to UVB (0,05J/cm2) twice a day for 4 days, being senescence state achieved by day 9.

Another extrinsic aging model we work with is the tBHP model. tBHP is an oxidant molecule that is used in industrial processes. Here, dermal fibroblasts are exposed to tBHP (40 µM) twice a day for 4 days, being senescence achieved by day 9 as well.

Molecular biology techniques such as western blot or qPCR are of help to study gene expression changes in our models. Moreover, mitochondrial structure is studied by confocal microscopy, and ROS production and mitochondrial membrane potential is studied by flow cytometry.

We also dispose of 3D models to study skin aging in a more physiological way. These are skin equivalents composed by an epidermis and a dermis. We study morphological changes using histochemical stains and check correct skin cells differentiation by immunofluorescence imaging of different skin layers markers. As we can observe in the last image, skin equivalents subjected to UVB irradiation show a disorganization of the epidermal layers and presence of dead cells. If you want to avoid these harmful consequences associated to photoaging, just wear sunscreen!