Highlights d Nutritional changes after birth alter b cell function d b cells acquire glucose response via changes in mTORC1 nutrient sensitivity d Glucose response is independent of changes in canonical b cell markers expression d Nutrient-regulated mTORC1 activity controls stem cellderived b cell function

Although aging is typically associated with a decline in maximal oxygen consumption (VO 2max ), young and old subjects, of similar initial muscle metabolic capacity, increased quadriceps VO 2max equally when this small muscle mass was trained in isolation. As it is unclear if this preserved exercise-induced plasticity with age is still evident with centrally challenging whole body exercise, we assessed maximal exercise responses in 13 young (24±2 years) and 13 old (60± 3 years) males, matched for cycling VO 2max (3.82±0.66 and 3.69±0.30 L min −1 , respectively), both before and after 8 weeks of high aerobic intensity cycle exercise training. As a consequence of the training both young and old significantly improved VO 2max (13±6 vs. 6± 7 %) and maximal power output (20±6 vs. 10±6 %, respectively) from baseline, however, the young exhibited a significantly larger increase than the old. Similarly, independently assessed maximal cardiac output (Q max ) tended to increase more in the young (16 ±14 %) than in the old (11±12 %), with no change in a-vO 2 difference in either group. Further examination of the components of Q max provided additional evidence of reduced exercise-induced plasticity in both maximal heart rate (young −3 %, old 0 %) and stroke volume (young 19± 15, old 11± 11 %) in the old. In combination, these findings imply that limited central cardiovascular plasticity may be responsible, at least in part, for the attenuated response to whole body exercise training with increasing age.

Modifying effects of curcumin (derived from the rhizome of Curcuma longa L.) during the initiation or post-initiation phase of N-nitrosomethylbenzylamine (NMBA)-induced esophageal carcinogenesis were investigated in male F344 rats. Five-week-old rats were divided into 5 groups, and groups 1, 2 and 3 were given intraperitoneal injections of NMBA (0.5 mg/kg body weight/injection 15 times) for 5 weeks from 7 weeks old to induce esophageal neoplasms. Groups 2 and 3 were fed the diet containing 500 ppm curcumin during the initiation and post-initiation phases, respectively. Group 4 was given the diet containing curcumin throughout the experiment, and group 5 was kept on the basal diet alone and served as an untreated control. Incidence and multiplicity of esophageal neoplasms of group 1 (NMBA alone) were 66.7% and 0.83 ± ± ± ±0.70, respectively. Those of groups 2 and 3 were significantly less than those of group 1 (39.3%, 0.46 ± ± ± ±0.64, P < < < <0.05; 33.3%, 0.36 ± ± ± ±0.56, P < < < <0.05, respectively). Furthermore, the incidence and multiplicity of esophageal preneoplastic lesions (moderate or severe epithelial dysplasia) of group 2 (57.1%, 0.61 ± ± ± ±0.57; 40%, 0.29 ± ± ± ±0.46) or 3 (56.7%, 0.67 ± ± ± ±0.66; 23.3%, 0.23 ± ± ± ±0.43) were less than those of group 1 (100%, 1.67 ± ± ± ±0.70; 70.8%, 0.92 ± ± ± ±0.72) (P < < < <0.05). In this experiment, feeding of curcumin significantly decreased the expression of cell proliferation biomarkers (5-bromo-2′ ′ ′ ′-deoxyuridine labeling index) in the non-lesional esophageal epithelium (P < < < <0.01). These findings indicate that curcumin inhibits NMBA-induced esophageal carcinogenesis when given during the post initiation as well as initiation phase. This inhibition may be related to suppression of the increased cell proliferation induced by NMBA in the esophageal epithelium.

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To prevent physical frailty and declines in cognitive function in older adults, regular physical activity and exercise training have been considered indispensable. Little information is known, however, on what kind of exercise training can simultaneously improve both physical and cognitive function. We have developed a novel fall and dementia program called "Square-Stepping Exercise" (SSE), which can induce functional activation of the brain and has previously demonstrated a short-term (3 months) effect in older Japanese people. PURPOSE:To investigate a relatively long-term (1 year) effect of regular SSE on cognitive and physical function in community-dwelling Japanese older women. METHODS:Participants were assigned to two groups: a SSE group (n = 41, mean age 70.7 ± 3.4 years) in which participants voluntarily continued the SSE program one or two times per week for 1 year after they took part in a supervised 3-month SSE class, and a control (C) group (n = 51, mean age 72.2 ± 5.3 years) who were randomly drawn from the basic resident register. Cognitive function was evaluated by the Five Cognitive Function Test. RESULTS:In comparisons between baseline and 1-year follow-up, significant improvements were observed in the SSE group in physical function parameters such as walking ability (p < 0.001), hand dexterity (p=0.013) and reaction time (p = 0.008), while significant declines were observed in the C group in balance ability (p = 0.016), walking ability (p = 0.007) and reaction time (p = 0.0025). An increase in the cognitive function score was greater in the SSE group (+16%: 68.8 ± 16.6∅79.8 ± 17.4, p<0.001) compared with the C group (+3%: 69.2 ± 15.2∅71.0 ± 17.1, p = 0.006). CONCLUSIONS:These results suggest that voluntarily participating in SSE for one year following a supervised SSE class can maintain or improve cognitive and physical function in older women. (No relationships reported)PURPOSE: Endurance performance declines with age. It is uncertain to what extent this is due to the ageing process or may be a result of reduced activity. This study investigated responses to aerobic endurance training in young and old with the same aerobic capacity baseline.METHODS: 24 ± 3yr (n=13) and 60±3yr (n=13) old males were matched on initial maximal oxygen consumption (VO2max ) (3.8 ± 0.7 L · min -1 and 3.7 ± 0.4 L · min -1 , respectively) and then trained high aerobic intensity cycling (4x4min) 3 times a week for 8 weeks. All subjects were unfamiliar with the training modality. RESULTS:Both groups improved VO2max and power output (W) from baseline, but young showed a larger increase than old (12.8 ± 5.5% vs. 7.6 ± 9.8% and 19.8 ± 4.7% vs. 14.4 ± 7.1%, p<0.05, respectively). Cardiac output, maximal stroke volume, and arteriovenous oxygen difference increased from pre to posttest within groups (p<0.05), but no differences between groups were observed (p=0.301; p=0.193; p=0.384, respectively). There were no differences in bodyweight (kg) between groups at pretest (76 ± 11 and 77 ± 6) or following the training intervention ...