Cellular energetics and mitochondrial uncoupling in canine aging.

The first domesticated companion animal, the dog, is currently represented by over 190 unique breeds. Across these numerous breeds, dogs have exceptional variation in lifespan (inversely correlated with body size), presenting an opportunity to discover longevity-determining traits. We performed a genome-wide association study on 4169 canines representing 110 breeds and identified novel candidate regulators of longevity. Interestingly, known functions within the identified genes included control of coat phenotypes such as hair length, as well as mitochondrial properties, suggesting that thermoregulation and mitochondrial bioenergetics play a role in lifespan variation. Using primary dermal fibroblasts, we investigated mitochondrial properties of short-lived (large) and long-lived (small) dog breeds. We found that cells from long-lived breeds have more uncoupled mitochondria, less electron escape, greater respiration, and capacity for respiration. Moreover, our data suggest that long-lived breeds have higher rates of catabolism and ß-oxidation, likely to meet elevated respiration and electron demand of their uncoupled mitochondria. Conversely, cells of short-lived (large) breeds may accumulate amino acids and fatty acid derivatives, which are likely used for biosynthesis and growth. We hypothesize that the uncoupled metabolic profile of long-lived breeds likely stems from their smaller size, reduced volume-to-surface area ratio, and therefore a greater need for thermogenesis. The uncoupled energetics of long-lived breeds lowers reactive oxygen species levels, promotes cellular stress tolerance, and may even prevent stiffening of the actin cytoskeleton. We propose that these cellular characteristics delay tissue dysfunction, disease, and death in long-lived dog breeds, contributing to canine aging diversity.

Management of the poorly prepared colonoscopy patient: colonoscopic colon enemas as a preparation for colonoscopy.

PURPOSE: Colonoscopic colon enema is an option for the management of patients who are suboptimally prepared for colonoscopic examination because of retained fecal material. METHODS: After colonoscopy is performed and the colonoscopist has reached the right colon and the colon is deemed to be inadequately prepared, the contents of two commercially available bisacodyl enemas are combined and instilled into the right colon via the colonoscope biopsy channel. Patients are allowed to recover from propofol sedation, expel the lumenal contents, resedated, and examined. RESULTS: In this fashion, 21 patients during a 19-month period were successfully cleansed of their retained fecal contents, permitting satisfactory colonoscopic examinations. This avoided the need for postponement of the procedure. CONCLUSIONS: Colonoscopic colon enema is an innovative and simple option available to the colonoscopist to manage the patient with an inadequately prepared colon.