Complementariness of experimental approaches to address research questions in older people

Vascular disease has been involved in the pathophysiology of frailty. However, the role of endothelial dysfunction, an obligatory step preceding vascular disease, is unknown. We addressed this issue in two phases: – searching if aging per se is accompanied by endothelial dysfunction in microvessels from human beings of different ages (range 18-89) free of cardiovascular risk factors or cardiovascular disease; – searching if endothelial dysfunction (assessed by high ADMA levels) is associated to frailty in older people enrolled in a cohort study (Toledo Study of Healthy Aging). Results Endothelial dysfunction is present in older people due to an increased oxidative stress and the presence of inflammation in the vascular wall (Rodriguez Manas et al., Aging Cell 2009) and ADMA levels are higher in frail people, in people without cardiovascular disease and after adjustment by Ankle-Brachial Index as a biomarker of subclinical disease (Alonso-Bouzon et al., Age 2013). Conclusion Different experimental approaches (from the bench to the population-based studies) exhibit a nice complementariness to ask research questions in older people. These findings have raised new hypotheses that are now being tested in EU funded projects (FRAILOMIC, FRAILCLINIC) led by our group to test biomarkers useful for the diagnosis and prognosis of frailty.