Beneficial Effects of a Q-ter® Based Nutritional Mixture on Functional Performance, Mitochondrial Function, and Oxidative Stress in Rats

BackgroundMitochondrial dysfunction and oxidative stress are central mechanisms underlying the aging process and the pathogenesis of many age-related diseases. Selected antioxidants and specific combinations of nutritional compounds could target many biochemical pathways that affect both oxidative stress and mitochondrial function and, thereby, preserve or enhance physical performance.Methodology/principal findingsIn this study, we evaluated the potential anti-aging benefits of a Q-ter based nutritional mixture (commercially known as Eufortyn) mainly containing the following compounds: terclatrated coenzyme Q(10) (Q-ter), creatine and a standardized ginseng extract. We found that Eufortyn supplementation significantly ameliorated the age-associated decreases in grip strength and gastrocnemius subsarcolemmal mitochondria Ca(2+) retention capacity when initiated in male Fischer344 x Brown Norway rats at 21 months, but not 29 months, of age. Moreover, the increases in muscle RNA oxidation and subsarcolemmal mitochondrial protein carbonyl levels, as well as the decline of total urine antioxidant power, which develop late in life, were mitigated by Eufortyn supplementation in rats at 29 months of age.Conclusions/significanceThese data imply that Eufortyn is efficacious in reducing oxidative damage, improving the age-related mitochondrial functional decline, and preserving physical performance when initiated in animals at early midlife (21 months). The efficacy varied, however, according to the age at which the supplementation was provided, as initiation in late middle age (29 months) was incapable of restoring grip strength and mitochondrial function. Therefore, the Eufortyn supplementation may be particularly beneficial when initiated prior to major biological and functional declines that appear to occur with advancing age

Beneficial effects of a Q-ter based nutritional mixture on functional performance, mitochondrial function, and oxidative stress in rats.

BackgroundMitochondrial dysfunction and oxidative stress are central mechanisms underlying the aging process and the pathogenesis of many age-related diseases. Selected antioxidants and specific combinations of nutritional compounds could target many biochemical pathways that affect both oxidative stress and mitochondrial function and, thereby, preserve or enhance physical performance.Methodology/principal findingsIn this study, we evaluated the potential anti-aging benefits of a Q-ter based nutritional mixture (commercially known as Eufortyn) mainly containing the following compounds: terclatrated coenzyme Q(10) (Q-ter), creatine and a standardized ginseng extract. We found that Eufortyn supplementation significantly ameliorated the age-associated decreases in grip strength and gastrocnemius subsarcolemmal mitochondria Ca(2+) retention capacity when initiated in male Fischer344 x Brown Norway rats at 21 months, but not 29 months, of age. Moreover, the increases in muscle RNA oxidation and subsarcolemmal mitochondrial protein carbonyl levels, as well as the decline of total urine antioxidant power, which develop late in life, were mitigated by Eufortyn supplementation in rats at 29 months of age.Conclusions/significanceThese data imply that Eufortyn is efficacious in reducing oxidative damage, improving the age-related mitochondrial functional decline, and preserving physical performance when initiated in animals at early midlife (21 months). The efficacy varied, however, according to the age at which the supplementation was provided, as initiation in late middle age (29 months) was incapable of restoring grip strength and mitochondrial function. Therefore, the Eufortyn supplementation may be particularly beneficial when initiated prior to major biological and functional declines that appear to occur with advancing age

Aptamers for Addressed Boron Delivery in BNCT: Effect of Boron Cluster Attachment Site on Functional Activity

Among the great variety of anti-cancer therapeutic strategies, boron neutron capture therapy (BNCT) represents a unique approach that doubles the targeting accuracy due to the precise positioning of a neutron beam and the addressed delivery of boron compounds. We have recently demonstrated the principal possibility of using a cell-specific 2′-F-RNA aptamer for the targeted delivery of boron clusters for BNCT. In the present study, we evaluated the amount of boron-loaded aptamer inside the cell via two independent methods: quantitative real-time polymerase chain reaction and inductive coupled plasma–atomic emission spectrometry. Both assays showed that the internalized boron level inside the cell exceeds 1 × 109 atoms/cell. We have synthesized closo-dodecaborate conjugates of 2′-F-RNA aptamers GL44 and Waz, with boron clusters attached either at the 3′- or at the 5′-end. The influence of cluster localization was evaluated in BNCT experiments on U-87 MG human glioblastoma cells and normal fibroblasts and subsequent analyses of cell viability via real-time cell monitoring and clonogenic assay. Both conjugates of GL44 aptamer provided a specific decrease in cell viability, while only the 3′-conjugate of the Waz aptamer showed the same effect. Thus, an individual adjustment of boron cluster localization is required for each aptamer. The efficacy of boron-loaded 2′-F-RNA conjugates was comparable to that of 10B-boronophenylalanine, so this type of boron delivery agent has good potential for BNCT due to such benefits as precise targeting, low toxicity and the possibility to use boron clusters made of natural, unenriched boron

The composition of Eufortyn® powder used for integration into animal supplementation pellets by Bio-Serv.

<p>The Eufortyn® supplementation food pellets and control bacon flavour pellets for the animals were prepared by Bio-Serv (Frenchtown, NJ) utilizing an effective bacon flavour masking capability in a grain-based diet.</p

Eufortyn® supplementation affected grip strength in rats at 21 months of age.

<p>In the control groups, there was a significant age-related decline in grip strength (age, <i>p</i><0.01, one-way ANOVA). Post-hoc analysis showed a decline in 21- and 29-month-old rats (**<i>p</i><0.01, Tukey's multiple comparison test) as compared to 8-month-old control cohort. There was a significant increase in grip strength in 21-month-old rats fed Eufortyn® as compared to their age-matched controls after 4 weeks of treatment (^#<i>p</i><0.05, Tukey's multiple comparison test). Values are means ± SEM (n = 7−14).</p

Eufortyn® significantly improved the calcium retention capacity in muscle subsarcolemmal mitochondria (SSM) in 21-month-old rats.

<p>(A) The maximum amount of Ca²⁺ required for mitochondrial PTP opening was measured on freshly isolated IFM and SSM. The calcium retention capacity of the SSM for control rats at 8, 21 and 29 months of age decreased significantly with age (age, <i>p</i><0.05, one-way ANOVA). However, the decrease in the calcium uptake capacity in SSM of 21-month-old rats was significantly ameliorated by Eufortyn® supplementation (^#<i>p</i><0.05, Tukey's multiple comparison test). (B) The calcium retention capacity of IFM for rats at 8, 21, and 29 months of age did not change over time and there was no statistical difference in the IFM calcium uptake capacity between control and treatment animals at 21 and 29 months of age. Values are means ± SEM (n = 7−14).</p

RNA and DNA oxidative damage in gastrocnemius muscle.

<p>(A) Post-hoc analysis showed that there is a tendency for greater level of RNA oxidation in 29-month-old rats compared to 8-month-old control (<i>p</i> = 0.09, Tukey's multiple comparison test). In addition, Eufortyn® significantly decreases RNA oxidative damage in 29-month-old rats (^#<i>p</i><0.05, Tukey's multiple comparison test). (B) DNA oxidative damage did not change over time for control animals. Values are means ± SEM (n = 7−8).</p

Total urine antioxidant power for male F344BNF1 rats.

<p>Values are means ± SEM (n = 3−7).</p>a,b<p>Different letters are significantly different from each other (<i>p</i><0.001 by Tukey's Multiple Comparison Test).</p