An intergenerational programme delays health impairment in nursing home residents: the Duplo project.

PURPOSE: To analyse whether an intergenerational programme in which students interacted with institutionalised older persons had any impact on the older persons' functional status. METHODS: Each academic year, a group of older adults living in nursing homes were divided into two arms. For the next four months, the first group received daily visits from a group of students during which they followed a pre-established activity plan, whilst the other arm proceeded with their normal activity. After 4 months, the groups crossed over, and the second arm received the student visits, whilst the first group returned to their normal activity. A battery of tests was performed at inception, crossover and the end of the second period. The tests explored mobility (Timed Up-and-Go), cognition (Mini-Mental Examination), executive function (Frontal Assessment Battery) and mood (Geriatric Depression Scale). A dichotomous aggregate "significant impairment" variable was deemed to be present when there was at least a 20% loss of function (compared to the value at the beginning of the period) in any of the aforementioned tests. RESULTS: The study included 289 older adults who visited with 91 students. Subjects in the active phase had a lower incidence of significant impairment than those in the control phase (O.R. 0.90, p < 0.01). There were no significant differences in the individual variables. CONCLUSION: An intergenerational project with students visiting older adults in nursing homes had a protective effect, delaying functional decay in older adults.

PWD/Ph-Encoded Genetic Variants Modulate the Cellular Wnt/ß-Catenin Response to Suppress Apc Min-Triggered Intestinal Tumor Formation.

Genetic predisposition affects the penetrance of tumor-initiating mutations, such as APC mutations that stabilize ß-catenin and cause intestinal tumors in mice and humans. However, the mechanisms involved in genetically predisposed penetrance are not well understood. Here, we analyzed tumor multiplicity and gene expression in tumor-prone Apc Min/+ mice on highly variant C57BL/6J (B6) and PWD/Ph (PWD) genetic backgrounds. (B6 × PWD) F1 APC Min offspring mice were largely free of intestinal adenoma, and several chromosome substitution (consomic) strains carrying single PWD chromosomes on the B6 genetic background displayed reduced adenoma numbers. Multiple dosage-dependent modifier loci on PWD chromosome 5 each contributed to tumor suppression. Activation of ß-catenin-driven and stem cell-specific gene expression in the presence of Apc Min or following APC loss remained moderate in intestines carrying PWD chromosome 5, suggesting that PWD variants restrict adenoma initiation by controlling stem cell homeostasis. Gene expression of modifier candidates and DNA methylation on chromosome 5 were predominantly cis controlled and largely reflected parental patterns, providing a genetic basis for inheritance of tumor susceptibility. Human SNP variants of several modifier candidates were depleted in colorectal cancer genomes, suggesting that similar mechanisms may also affect the penetrance of cancer driver mutations in humans. Overall, our analysis highlights the strong impact that multiple genetic variants acting in networks can exert on tumor development. SIGNIFICANCE: These findings in mice show that, in addition to accidental mutations, cancer risk is determined by networks of individual gene variants.