RBP4 in Ageing

Background: The protein that binds to retinol 4 (RBP4), is a lipocalin-family protein, secreted primarily by the adipose tissue and the liver, and has also been reported to be produced by other tissues, including the kidney. This protein mediates the transport of vitamin A (retinol) in the circulation, bound to a transporter protein, transthyretin. In recent years, RBP4 has been shown to contribute to the development of insulin resistance and a range of metabolic disorders such as type 2 diabetes mellitus, gestational diabetes, obesity, metabolic syndrome, hyperuricaemia, metabolic dysfunction-associated steatotic liver disease (MASLD), and cardiorenal diseases. Objectives: The objective was to analyse the role of RBP4 in ageing, as well as its mechanisms and effects across organs and systems. Results: Circulating RBP4 levels increase with age and have been related to the onset of various processes like sarcopenia, elevated neurodegenerative markers in the brain, and an increase in TSH levels. Furthermore, it appears that in ageing, the rise in RBP4 is related to the development of atherogenesis, chronic kidney disease, and osteoarthritis. These effects appear to be mediated by chronic inflammation along with the development of insulin resistance, increased oxidative stress and mitochondrial dysfunction, inhibition of autophagy, and intestinal dysbiosis. Conclusions: RBP4 is a factor to be taken into account in the ageing process, as it has been shown that elevated circulating serum levels in older individuals lead to and accelerate deterioration across different organs or systems.