Caveolin-1, cellular senescence and age-related diseases

Abstract

According to the “free radical theory” of aging, normal aging occurs as the result of tissue damages inflicted by reactive oxygen species (ROS) when ROS production exceeds the antioxidant capacity of the cell. ROS induce cellular dysfunctions such as stress-induced premature senescence (SIPS), which is believed to contribute to normal organismal aging and play a role in age-related diseases. Consistent with this hypothesis, increased oxidative damage of DNA, proteins, and lipids have been reported in aged animals and senescent cells accumulate in vivo with advancing age. Caveolin-1 acts as a scaffolding protein that concentrates and functionally regulates signaling molecules. Recently, great progress has been made toward understanding of the role of caveolin-1 in stress-induced premature senescence. Data show that caveolin-mediated signaling may contribute to explain, at the molecular level, how oxidative stress promotes the deleterious effects of cellular senescence such as aging and age-related diseases. In this review, we discuss the cellular mechanisms and functions of caveolin-1 in the context of SIPS and their relevance to the biology of aging.

Caveolin-1/PTRF upregulation constitutes a mechanism for mediating p53-induced cellular senescence: implications for evidence-based therapy of delayed wound healing in diabetes

“…Consistent with these findings, Cav-1 expression is also elevated in various tissues of old animals, including the lungs, spleens, and brains (28,38). This involvement of Cav-1 in replicative senescence can be recapitulated when cells or tissues are exposed to excessive levels of oxidative stress (56). For example, it was shown that a sublethal HP level increases endogenous Cav-1 expression and induces premature senescence in NIH 3T3 cells (51).…”

“…In this vein, old human fibroblasts and replicative senescent mesenchymal stem cells and bone marrow stromal cells have been shown to express higher levels of Cav-1 compared with their control counterparts (56). Moreover, Cav-1 upregulation positively correlates with the reduced replicative lifespan of chondrocytes following treatment with interleukin-1␤ (54).…”

Loss of Epithelial Membrane Protein 2 Aggravates Podocyte Injury via Upregulation of Caveolin-1

“…[18][19][20] Indeed, it has been reported that Mdm2 regulates p53-mediated podocyte apoptosis. 21,22 Therefore, it is possible that excessive CAV1 in podocytes will deregulate the p53 pathway and affect podocyte survival.…”

Combinación de fibrosis pulmonar y enfisema: una entidad poco reconocida

“…La mutación en las telomerasas (enzimas reguladoras del envejecimiento celular) se ha identificado como un factor de riesgo para desarrollar fibrosis pulmonar (descrita en el 15-20% de pacientes con fibrosis pulmonar idiopática) (21). Por otra parte, en el enfisema se describe alteración en las telomerasas relacionada con la exposición crónica al humo de cigarrilo.…”

“…Su sobreexpresión condiciona hiperplasia de células epiteliales alveolares con fibrosis pulmonar secundaria (en zonas de estrés mecánico) (21)(22)(23). En el enfisema se ha descrito inhibición de la vía Wnt mediada por productos de degradación del tabaco, que produce disminución en el número de células epiteliales alveolares con destrucción secundaria del parénquima pulmonar (23,24).…”