Multivariate analysis of independent determinants of ADL/IADL and quality of life in the elderly.

BACKGROUND: This study evaluated the determinants of disability and quality of life in elderly people who participated at the multi-centred RubiN project (Regional ununterbrochen betreut im Netz) in Germany. METHODS: Baseline data of the subjects aged 70 years and older of the RubiN project were used and only subjects with complete data sets were considered for the ensuing analysis (complete case analysis (CCA)). Disability was examined using the concepts of ADL (activities of daily living) and IADL (instrumental activities of daily living). Subjects exhibiting one or more deficiencies in ADL respectively IADL were considered as ADL respectively IADL disabled. Quality of life was assessed using the WHOQOL-BREF and the WHOQOL-OLD. Applying multivariate analysis, sociodemographic factors, psychosocial characteristics as well as the functional, nutritional and cognitive status were explored as potential determinants of disability and quality of life in the elderly. RESULTS: One thousand three hundred seventy-five subjects from the RubiN project exhibited data completeness regarding baseline data. ADL and IADL disability were both associated with the respective other construct of disability, sex, a reduced cognitive and functional status as well as domains of the WHOQOL-BREF. Furthermore, ADL disability was related to social participation, while IADL disability was linked to age, education and social support. Sex, ADL and IADL disability, income, social support and social participation as well as the functional status were predictors of the domain 'Physical Health' (WHOQOL-BREF). The facet 'Social Participation' (WHOQOL-OLD) was affected by both ADL and IADL disability, income, social participation, the nutritional and also the functional status. CONCLUSIONS: Several potential determinants of disability and quality of life were identified and confirmed in this study. Attention should be drawn to prevention schemes as many of these determinants appear to be at least partly modifiable.

Yap reprograms glutamine metabolism to increase nucleotide biosynthesis and enable liver growth.

The Hippo pathway is an important regulator of organ size and tumorigenesis. It is unclear, however, how Hippo signalling provides the cellular building blocks required for rapid growth. Here, we demonstrate that transgenic zebrafish expressing an activated form of the Hippo pathway effector Yap1 (also known as YAP) develop enlarged livers and are prone to liver tumour formation. Transcriptomic and metabolomic profiling identify that Yap1 reprograms glutamine metabolism. Yap1 directly enhances glutamine synthetase (glul) expression and activity, elevating steady-state levels of glutamine and enhancing the relative isotopic enrichment of nitrogen during de novo purine and pyrimidine biosynthesis. Genetic or pharmacological inhibition of GLUL diminishes the isotopic enrichment of nitrogen into nucleotides, suppressing hepatomegaly and the growth of liver cancer cells. Consequently, Yap-driven liver growth is susceptible to nucleotide inhibition. Together, our findings demonstrate that Yap1 integrates the anabolic demands of tissue growth during development and tumorigenesis by reprogramming nitrogen metabolism to stimulate nucleotide biosynthesis.