Caveolin-1, cellular senescence and age-related diseases

• Published in: Mechanisms of ageing and development 2011-11, Vol.132 (11-12), p.533-542
• Main Authors: Zou, Huafei, Stoppani, Elena, Volonte, Daniela, Galbiati, Ferruccio
• Format: Article
• Language: English
• Subjects: Aging; Aging - metabolism; Aging - pathology; Animals; Atherosclerosis - etiology; Biological and medical sciences; Caveolin; Caveolin 1 - metabolism; Cell Proliferation; Cellular Senescence - physiology; Development. Metamorphosis. Moult. Ageing; Fibrosis; Fundamental and applied biological sciences. Psychology; Humans; Infection - etiology; Intervertebral Disc Degeneration - etiology; Models, Biological; Osteoarthritis - etiology; Oxidative Stress; p53; Pulmonary Emphysema - etiology; Reactive Oxygen Species - metabolism; Senescence; Signal Transduction; Tumor Microenvironment; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Wound Healing
• ISSN: 0047-6374; 1872-6216
• DOI: 10.1016/j.mad.2011.11.001

► Oxidative stress upregulates caveolin-1 protein expression. ► Caveolin-1 activates the p53/p21Waf1/Cip1 pathway. ► Caveolin-1 expression is required for stress-induced premature senescence. ► Caveolin-1 mediates age-related diseases in vivo. 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.