The primary aim of this study was to determine whether supplementation with calcium β-hydroxy-β-methylbutyrate (HMB) and Vitamin D3 (D) would enhance muscle function and strength in older adults. Older adults over 60 years of age with insufficient circulating 25-hydroxy-Vitamin D (25OH-D) levels were enrolled in a double-blinded controlled 12-month study. Study participants were randomly assigned to treatments consisting of: (a) Control + no exercise; (b) HMB+D + no exercise; (c) Control + exercise, and (d) HMB+D + exercise. The study evaluated 117 participants consisting of multiple measurements over the 12 months that included body composition, strength, functionality, and questionnaires. HMB+D had a significant benefit on lean body mass within the non-exercise group at 6 months (0.44±0.27kg, HMB+D vs. -0.33±0.28kg control, p<0.05). In non-exercisers, improvement in knee extension peak torque (60°/sec) was significantly greater in HMB+D supplemented participants than in non-supplemented group (p=0.04) at 3 months, 10.9 ± 5.7Nm and -5.2 ± 5.9Nm, respectively. A composite functional index, integrating changes in handgrip, Get Up, and Get Up and Go measurements, was developed. HMB+D + no exercise resulted in significant increases in the functional index compared to those observed in the control + no exercise group at 3 (p=0.03), 6 (p=0.04), and 12 months (p=0.04). Supplementation with HMB+D did not further improve the functional index within the exercising group. This study demonstrated the potential of HMB and Vitamin D3 supplementation to enhance muscle strength and physical functionality in older adults, even in individuals not engaged in an exercise training program

What is the central question of this study? In young adults, about half of the cold-related reduction in skin blood flow during cold exposure is mediated by noradrenaline, while the remainder is attributable to other substances co-released with noradrenaline that have yet to be identified. What is the main finding and its importance? Purinergic receptor blockade blunted the vasoconstriction response to whole-body cooling and to intradermal administration of tyramine. These results indicate that ATP is necessary to vasoconstrict blood vessels in the skin adequately and prevent heat loss in a cold environment. Noradrenaline is responsible for eliciting ∼60% of the reflex cutaneous vasoconstriction (VC) response in young adults, while the remainder is attributable to one or more unidentified co-released sympathetic adrenergic neurotransmitter(s). Inconsistent evidence has placed neuropeptide Y in this role; however, other putative cotransmitters have yet to be tested. We hypothesize that ATP contributes to the reflex cutaneous VC response. Two protocols were conducted in young adults (n = 10); both involved the placement of three microdialysis probes in forearm skin and whole-body cooling (skin temperature = 30.5°C). In protocol 1, the following solutions were infused: (i) lactated Ringer solution (control); (ii) 10 mm l-NAME; and (iii) purinergic receptor blockade with 1 mm suramin plus l-NAME. In protocol 2, the following solutions were infused: (i) lactated Ringer solution; (ii) suramin plus l-NAME; and (iii) suramin plus l-NAME plus adrenoreceptor blockade with 5 mm yohimbine plus 1 mm propranolol. Laser Doppler flux (LDF) was measured over each microdialysis site, and cutaneous vascular conductance (CVC) was calculated (CVC = LDF/MAP) and expressed as percentage changes from baseline (%ΔCVC ). l-NAME was used to block the vasodilatory influence of ATP and unmask the P X-mediated VC response to exogenous ATP infusion (-21 ± 6%ΔCVC ). During cooling, the VC response (control, -39 ± 8%ΔCVC ) was attenuated at the suramin site (-21 ± 4%ΔCVC ) and further blunted with combined adrenoreceptor blockade (-9 ± 3%ΔCVC ; P < 0.05). Compared with the control site (-22 ± 5%ΔCVC ), suramin inhibited pharmacologically induced VC to tyramine (-12 ± 6%ΔCVC ; P < 0.05), which displaces adrenergic neurotransmitters from axon terminals. These data indicate that ATP contributes to the cutaneous VC response in humans.

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Angiotensin II (ANG II) is locally produced in human skin and contributes to the reflex vasoconstriction (VC) response in aged but not young skin. We hypothesized that the exogenous ANG II-mediated VC response would be greater in older adults and would be affected by inhibition of adrenoreceptor or ANG II type II receptor (AT2R) pathways. Three microdialysis (MD) fibers were placed in the forearm skin of 11 young (26 ± 3 yr) and 11 older (68 ± 4 yr) individuals for perfusion of 1) Ringer solution (control), 2) adrenoreceptor blockade with yohimbine + propranolol, and 3) AT2R inhibition with PD-123319. ANG II was then added to the perfusates at eight graded dose concentrations ranging from 10−10 to 10−3 M. Laser Doppler flux was measured at each MD site, and cutaneous vascular conductance (CVC) was calculated as CVC =  laser Doppler flux/mean arterial pressure and normalized to baseline CVC values collected before ANG II perfusion (%ΔCVCbaseline). At the control site, older adults (−34 ± 4%ΔCVCbaseline) exhibited a greater peak VC compared with young adults (−22 ± 2%ΔCVCbaseline, P < 0.05), which was attenuated with adrenoreceptor blockade. Young skin exhibited a vasodilation in response to lower ANG II doses that was inhibited with AT2R inhibition. AT2R inhibition also increased the VC response to higher ANG II doses such that young skin responded similarly to older skin. These results indicate that ANG II has a greater VC influence in older than young individuals. Furthermore, ANG II may be affecting multiple targets, including adrenergic and AT2R pathways. NEW & NOTEWORTHY Intradermal perfusion of successive doses of angiotensin II (ANG II) revealed a role for ANG II type II receptors and dose-dependent, ANG II-mediated vasodilation in young but not older adults. In contrast, older adults exhibited greater vasoconstriction for a given dose of ANG II. The increased vasoconstriction in older adults was subsequently blunted with adrenoreceptor blockade, which indicates an interaction between ANG II and adrenergic signaling pathways in the cutaneous microcirculation.

Introduction During cold exposure, an increase in sympathetic nerve activity evokes vasoconstriction (VC) of cutaneous vessels to minimize heat loss. In older adults, this reflex VC response is impaired thereby increasing their susceptibility to excess heat loss and hypothermia. Because l-tyrosine, the amino acid substrate necessary for catecholamine production, has been shown to augment reflex VC in age skin, we hypothesize that oral ingestion of l-tyrosine will attenuate the decline in core temperature (T c) during whole-body cooling in older adults. Methods In a randomized, double-blind design, nine young (25 ± 3 yr) and nine older (72 ± 8 yr) participants ingested either 150 mg·kg−1 of l-tyrosine or placebo before commencing 90 min of whole-body cooling to decrease skin temperature to approximately 29.5°C. Esophageal temperature and forearm laser Doppler flux (LDF) were measured continuously throughout the protocol to provide an index of T c and skin blood flow, respectively. The change in esophageal temperature (ΔT ES) was the difference in temperature at the end of cooling subtracted from baseline. Cutaneous vascular conductance (CVC) was calculated as CVC = LDF/mean arterial pressure and expressed as a percent change from baseline (%ΔCVCBASELINE). Results Oral tyrosine ingestion augmented the cutaneous VC response to cooling in older adults (placebo, 14.4 ± 2.0; tyrosine, 32.7% ± 1.7% ΔCVCBASELINE; P < 0.05). Additionally, tyrosine improved T c maintenance throughout cooling in older adults (placebo, −0.29 ± 0.07; tyrosine, −0.07 ± 0.07 ΔT ES; P < 0.05). Both the cutaneous VC and T c during cooling were similar between young and older adults supplemented with tyrosine (P > 0.05). Conclusions These results indicate that l-tyrosine supplementation improves T c maintenance in response to acute cold exposure in an older population.