Effects of slow- v. fast-digested protein supplementation combined with mixed power training on muscle function and functional capacities in older men.

Ageing leads to a progressive loss of muscle function (MF) and quality (MQ: muscle strength (MS)/lean muscle mass (LM)). Power training and protein (PROT) supplementation have been proposed as efficient interventions to improve MF and MQ. Discrepancies between results appear to be mainly related to the type and/or dose of proteins used. The present study aimed at determining whether or not mixed power training (MPT) combined with fast-digested PROT (F-PROT) leads to greater improvements in MF and MQ in elderly men than MPT combined with slow-digested PROT (S-PROT) or MPT alone. Sixty elderly men (age 69 (sd 7) years; BMI 18-30 kg/m2) were randomised into three groups: (1) placebo + MPT (PLA; n 19); (2) F-PROT + MPT (n 21) and (3) S-PROT + MPT (n 20) completed the intervention. LM, handgrip and knee extensor MS and MQ, functional capacity, serum metabolic markers, skeletal muscle characteristics, dietary intake and total energy expenditure were measured. The interventions consisted in 12 weeks of MPT (3 times/week; 1 h/session) combined with a supplement (30 g:10 g per meal) of F-PROT (whey) or S-PROT (casein) or a placebo. No difference was observed among groups for age, BMI, number of steps and dietary intake pre- and post-intervention. All groups improved significantly their LM, lower limb MS/MQ, functional capacity, muscle characteristics and serum parameters following the MPT. Importantly, no difference between groups was observed following the MPT. Altogether, adding 30 g PROT/d to MPT, regardless of the type, does not provide additional benefits to MPT alone in older men ingesting an adequate (i.e. above RDA) amount of protein per d.

Intakes of folate, vitamin B6 and B12 and risk of depression in community-dwelling older adults: the Quebec Longitudinal Study on Nutrition and Aging.

BACKGROUND/OBJECTIVES: Depression can decrease quality of life and affect health outcomes in older population. We investigated whether different intake levels of folate, vitamin B6 and B12 were associated with a 3-year depression incidence among generally healthy, community-dwelling older men and women. SUBJECTS/METHODS: Participants in the Québec Longitudinal Study on Nutrition and Aging (NuAge), free of depression (that is, 30-item Geriatric Depression Scale (GDS) <11) at baseline (N=1368; 74 ± 4 years old; 50.5% women), were screened annually for incident depression (GDS ⩾ 11) or antidepressant medication. Tertiles of intakes (food only and food+supplements) were obtained from the mean of three non-consecutive 24-h recalls at baseline. Sex-stratified multiple logistic regression models were adjusted for age, physical activity, physical functioning, stressful life events and total energy intake. RESULTS: Over 3 years, 170 participants were identified as depressed. Women in the highest tertile of B6 intake from food were 43% less likely to become depressed when adjusting for demographic and health factors (multivariate odds ratio (OR) 0.57, 95% confidence interval (CI) 0.39-0.96), but adjustment for energy intake attenuated the effect. Men in the highest tertile of dietary B12 intake had decreased risk of depression (energy-adjusted multivariate OR 0.42, 95% CI 0.20-0.90). No other association was observed. CONCLUSIONS: This study provides some evidence of decreased depression risk among women with higher intakes of vitamin B6 from food, which was dependent on total energy intake, and among men with higher intakes of B12 from food, independently of energy intake.

Beta-amyloid-related peptides inhibit potassium-evoked acetylcholine release from rat hippocampal slices.

The 4 kDa beta-amyloid (A beta) protein, a major component of cerebral and cerebrovascular plaques in Alzheimer's disease (AD), is derived from the proteolytic cleavage of a larger, membrane-bound precursor, the A beta precursor protein (APP). Until recently, it was assumed that an aberrant AD-specific proteolysis generated A beta peptides, which subsequently could initiate and/or contribute to the pathological cascade leading to plaque formation and losses of selected neuronal populations, including basal forebrain cholinergic neurons that provide major inputs to the hippocampus and neocortex. However, the recent detection of soluble A beta fragments in the plasma and CSF of normal individuals, as well as in the conditioned media of cultured brain cells, suggests a role for A beta-related peptides in normal brain functions. Taking into consideration the reported toxic properties of A beta and the preferential vulnerability of basal forebrain cholinergic neurons in AD, we investigated the possible effects of A beta-related peptides on the release of endogenous acetylcholine (ACh) from rat brain slices. A beta 1-28, in a concentration-dependent manner (10(-12)-10(-8) M), potently inhibited K(+)-evoked ACh release from hippocampal slices. The inhibition of ACh release was fully reversible and was observed using other A beta-related peptides such as A beta 1-42, A beta 1-40, and A beta 25-35, but not with the scrambled, reverse, or all D-isomer A beta-peptide sequences, indicating that the effect of A beta on ACh release is mediated via a stereoselective mechanism. Tetrodotoxin (10 microM) failed to alter the effect of A beta 1-28 on ACh release, which suggests the lack of involvement of voltage-dependent Na+ channels. Except for the hippocampal formation, the inhibitory effect of A beta on K(+)-evoked ACh release also was observed in the frontal cortex but not in the striatum. Taken together, our results demonstrate that APP-derived A beta-related peptides can regulate the release of ACh potently by acting on cholinergic terminals. Additionally, the evidence that selected cholinergic neuronal populations are sensitive to A beta suggests a potential mechanistic link between the deposition of A beta and the preferential vulnerability of certain cholinergic projections in AD.

Proteolytic degradation of rat growth hormone-releasing factor(1-29) amide in rat pituitary and hypothalamus.

The identification of peptide bonds vulnerable to tissue peptidases is a valuable approach to design peptide agonists which exhibit a longer duration of action than the native molecules. Therefore, the kinetic of disappearance of rat growth hormone-releasing factor (rGRF(1-29)NH2) and the identification of its metabolites were studied in rat pituitary and hypothalamus. Synthetic rGRF(1-29)NH2 (10 microM) was incubated (0-120 min, 37 degrees C) in the presence of a pituitary (237 +/- 51 micrograms protein/ml) or hypothalamus homogenate (576 +/- 27 micrograms protein/ml). Using analytical high pressure liquid chromatography (HPLC), apparent half-lives of 22 +/- 3 min and 25 +/- 4 min were found in pituitary and hypothalamus, respectively. In both tissues, three degradation products, all less hydrophobic than the native peptide, were detected and isolated by preparative HPLC. The identification of the purified metabolites was ascertained by amino acid analysis, sequencing and chromatography with synthetic homologs. These results indicate that the main sites of cleavage in the pituitary and hypothalamus are Lys21-Leu22 (trypsin-like cleavage site), Leu14-Gly15 and Tyr10-Arg11 (chymotrypsin-like cleavage sites). TLCK and leupeptin did not affect the formation of fragment (1-21)OH while TPCK blocked the cleavage of Leu14-Gly15. The low affinity of fragment (1-21)NH2 for pituitary GRF binding sites suggests that hydrolysis of the Lys21-Leu22 bond inactivates rGRF(1-29)NH2 in this target tissue.

Dynamics of growth hormone responsiveness to growth hormone releasing factor in aging rats: peripheral and central influences.

The in vivo and in vitro dynamics of somatotroph responsiveness to rGRF (1-29) NH2 (rat growth hormone releasing factor) were evaluated in 2-, 4-, 8-, 12-, and 20-month-old male rats. In vivo, using pentobarbital-anesthetized animals, we observed that the rGH (rat growth hormone) responsiveness to 0.4 and 1.6 micrograms/kg rGRF started to decline at the higher dose in 12-month-old rats and was completely blunted at both rGRF doses in 20-month-old animals. In vitro, using freshly dispersed perifused pituitary cells, we also documented a decrease of rGRF-induced rGH secretion in 12- and 20-month-old rats. Moreover, as the animals aged, the rGRF-induced rGH secretion was differentially affected by the inhibiting action of somatostatin (p less than 0.001), suggesting a loss of pituitary sensitivity to somatostatin in the presence of a high concentration of rGRF. The pituitary rGH content increased until rats reached 12 months of age, but was diminished in 20-month-old rats. In contrast, the pituitary somatostatin content increased twofold in 20-month-old rats as compared with younger rats. The hypothalamic somatostatin content was highest in 8-month-old rats and only slightly diminished in 20-month-old animals. Finally, plasma insulin-like growth factor I concentrations were highest in 8-month-old rats and lowest in 20-month-old animals. Altogether, these results indicate that the physiological loss of somatotroph responsiveness associated with the process of aging starts around 12 months of age.(ABSTRACT TRUNCATED AT 250 WORDS)

Cleavage of aspartyl beta-phenacyl esters by selenophenol under neutral conditions.

Neutral selenophenol in DMF accomplished the removal of the beta-phenacyl protecting group of aspartic acid in solution, on the peptide Boc-Asp (beta-OPac)- Phe amide and on the resin peptide Boc-Trp(Nin-For)-Met-Asp (beta-OPac)-P (CCK 30-33) without alpha, beta-rearrangement.