Effect of age on in vivo rates of mitochondrial protein synthesis in human skeletal muscle

A progressive decline in muscle performance in the rapidly expanding aging population is causing a dramatic increase in disability and health care costs. A decrease in muscle endurance capacity due to mitochondrial decay likely contributes to this decline in muscle performance. We developed a novel stable isotope technique to measure in vivo rates of mitochondrial protein synthesis in human skeletal muscle using needle biopsy samples and applied this technique to elucidate a potential mechanism for the age-related decline in the mitochondrial content and function of skeletal muscle. The fractional rate of muscle mitochondrial protein synthesis in young humans (24 ± 1 year) was 0.081 ± 0.004%·h−1, and this rate declined to 0.047 ± 0.005%·h−1 by middle age (54 ± 1 year; P < 0.01). No further decline in the rate of mitochondrial protein synthesis (0.051 ± 0.004%·h−1) occurred with advancing age (73 ± 2 years). The mitochondrial synthesis rate was about 95% higher than that of mixed protein in the young, whereas it was approximately 35% higher in the middle-aged and elderly subjects. In addition, decreasing activities of mitochondrial enzymes were observed in muscle homogenates (cytochrome c oxidase and citrate synthase) and in isolated mitochondria (citrate synthase) with increasing age, indicating declines in muscle oxidative capacity and mitochondrial function, respectively. The decrease in the rates of mitochondrial protein synthesis is likely to be responsible for this decline in muscle oxidative capacity and mitochondrial function. These changes in muscle mitochondrial protein metabolism may contribute to the age-related decline in aerobic capacity and muscle performance.

Spatial memory is related to hippocampal subcellular concentrations of calcium-dependent protein kinase C isoforms in young and aged rats

Relationships were examined between spatial learning and hippocampal concentrations of the α, β2, and γ isoforms of protein kinase C (PKC), an enzyme implicated in neuronal plasticity and memory formation. Concentrations of PKC were determined for individual 6-month-old (n = 13) and 24-month-old (n = 27) male Long–Evans rats trained in the water maze on a standard place-learning task and a transfer task designed for rapid acquisition. The results showed significant relationships between spatial learning and the amount of PKC among individual subjects, and those relationships differed according to age, isoform, and subcellular fraction. Among 6-month-old rats, those with the best spatial memory were those with the highest concentrations of PKCγ in the particulate fraction and of PKCβ2 in the soluble fraction. Aged rats had increased hippocampal PKCγ concentrations in both subcellular fractions in comparison with young rats, and memory impairment was correlated with higher PKCγ concentrations in the soluble fraction. No age difference or correlations with behavior were found for concentrations of PKCγ in a comparison structure, the neostriatum, or for PKCα in the hippocampus. Relationships between spatial learning and hippocampal concentrations of calcium-dependent PKC are isoform-specific. Moreover, age-related spatial memory impairment is associated with altered subcellular concentrations of PKCγ and may be indicative of deficient signal transduction and neuronal plasticity in the hippocampal formation.

The Effects of Postural Loading, Sacral Orientation, and Age on Sex Differences in Lumbar Functional Morphology and Health

Thesis (Ph.D.)--University of Washington, 2016-06

Role of oxidative stress in age-associated chronic kidney pathologies

The kidneys exhibit age-associated deterioration in function via a loss of 20% to 25% kidney mass, particularly from the renal cortex and increased fibrosis. Oxidative stress has been found to mediate age-associated renal cell injury and cell death, particularly apoptosis. Oxidative stress results from an imbalance between the levels of free radicals generated during aerobic metabolism, inflammation, and infection and the safe breakdown of these species by endogenous and exogenous scavengers. Other factors may influence these pathologies. For example, growth hormone and caloric restriction have been shown to influence life span, although neither method of prolonging life is likely to find general acceptance in humans. Some genetic knockout models offer promise; for example, knockout of the p66 isoform of the Shc gene in mice increases life span by 30%, but appetite, size, and fertility are retained. Whether the increase in life span is via increased kidney health is not yet clear, but decreasing the age-related renal pathologies will no doubt aid in increasing life span and health in general. This review looks at the role and modulation of factors that influence life span, in particular modulation of oxidative stress, with particular relevance to age-related renal pathologies. (C) 2005 by the National Kidney Foundation, Inc.

Searching for the trace: The influence of age, lexical activation and working memory on sentence processing

To investigate the stability of trace reactivation in healthy older adults, 22 older volunteers with no significant neurological history participated in a cross-modal priming task. Whilst both object relative center embedded (ORC) and object relative right branching (ORR) sentences is-ere employed, working memory load was reduced by limiting the number of wordy separating the antecedent front the gap for both sentence types. Analysis of the results did not reveal any significant trace reactivation for the ORC or ORR sentences. The results did reveal, however, a positive correlation between age and semantic printing at the pre-gap position and a negative correlation between age and semantic printing at the gap position for ORC sentences. In contrast, there was no correlation between age and priming effects for the ORR sentences. These results indicated that trace reactivation may be sensitive to a variety of age related factors, including lexical activation and working memory. The implications of these results for sentence processing in the older population arc discussed.

Supervisor-subordinate age dissimilarity and performance ratings:the buffering effects of supervisory relationship practice

Using 394 pairs of employees and their immediate supervisors working in the Information and Communication Technology (ICT) sector in three northern European countries, this study examined the effect of workplace moderators on the link between relational demography and supervisor ratings of performance. Directional age differences between superior and subordinate (i.e., status incongruence caused when the supervisor is older or younger than his/her subordinate) and non-directional age differences were used as predictors of supervisor ratings of occupational expertise. The quality of the supervisor-subordinate relationship and the existence of positive age-related supervisory practices were examined as moderators of this relationship. The results provide no support for a relationship between directional age differences and age-related stereotyping by supervisors in ratings of performance, neither for the effects of age-related supervisory practices. However, high quality supervisor-subordinate relationships did moderate the effects of age dissimilarity on supervisory ratings. The implications of these findings for performance appraisal methodologies and recommendations for further research are discussed.

Does metabolic reprogramming underpin age-associated changes in T cell phenotype and function?

T cells are required for an effective adaptive immune response. The principal function of T cells is to promote efficient removal of foreign material by identifying and mounting a specific response to nonself. A decline in T cell function in aging is thought to contribute to reduced response to infection and vaccination and an increase in autoimmunity. This may in part be due to the age-related decrease in naïve CD4+ T cells and increase in antigen-experienced CD4+ T cells, loss of redox homeostasis, and impaired metabolic switching. Switching between subsets is triggered by the integration of extracellular signals sensed through surface receptors and the activation of discrete intracellular metabolic pathways. This article explores how metabolic programming and loss of redox homeostasis during aging may contribute to age-associated changes in T cell phenotype and function. © 2014 Elsevier Inc.

The influence on unaided vision of age, pupil diameter and spherocylindrical refractive error

Background - The aim was to derive equations for the relationship between unaided vision and age, pupil diameter, iris colour and sphero-cylindrical refractive error. Methods - Data were collected from 663 healthy right eyes of white subjects aged 20 to 70 years. Subjective sphero-cylindrical refractive errors ranged from -6.8 to +9.4 D (mean spherical equivalent), -1.5 to +1.9 D (orthogonal component, J0) and -0.8 to 1.0 D (oblique component, J45). Cylinder axis orientation was orthogonal in 46 per cent of the eyes and oblique in 18 per cent. Unaided vision (-0.3 to +1.3 logMAR), pupil diameter (2.3 to 7.5 mm) and iris colour (67 per cent light/blue irides) was recorded. The sample included mostly females (60 per cent) and many contact lens wearers (42 per cent) and so the influences of these parameters were also investigated. Results - Decision tree analysis showed that sex, iris colour, contact lens wear and cylinder axis orientation did not influence the relationship between unaided vision and refractive error. New equations for the dependence of the minimum angle of resolution on age and pupil diameter arose from step backwards multiple linear regressions carried out separately on the myopes (2.91.scalar vector +0.51.pupil diameter -3.14 ) and hyperopes (1.55.scalar vector + 0.06.age – 3.45 ). Conclusion - The new equations may be useful in simulators designed for teaching purposes as they accounted for 81 per cent (for myopes) and 53 per cent (for hyperopes) of the variance in measured data. In comparison, previously published equations accounted for not more than 76 per cent (for myopes) and 24 per cent (for hyperopes) of the variance depending on whether they included pupil size. The new equations are, as far as is known to the authors, the first to include age. The age-related decline in accommodation is reflected in the equation for hyperopes.

Age-associated changes in long-chain fatty acid profile during healthy aging promote pro-inflammatory monocyte polarization via PPARγ

Differences in lipid metabolism associate with age-related disease development and lifespan. Inflammation is a common link between metabolic dysregulation and aging. Saturated fatty acids (FAs) initiate pro-inflammatory signalling from many cells including monocytes; however, no existing studies have quantified age-associated changes in individual FAs in relation to inflammatory phenotype. Therefore, we have determined the plasma concentrations of distinct FAs by gas chromatography in 26 healthy younger individuals (age < 30 years) and 21 healthy FA individuals (age > 50 years). Linear mixed models were used to explore the association between circulating FAs, age and cytokines. We showed that plasma saturated, poly- and mono-unsaturated FAs increase with age. Circulating TNF-α and IL-6 concentrations increased with age, whereas IL-10 and TGF-β1 concentrations decreased. Oxidation of MitoSOX Red was higher in leucocytes from FA adults, and plasma oxidized glutathione concentrations were higher. There was significant colinearity between plasma saturated FAs, indicative of their metabolic relationships. Higher levels of the saturated FAs C18:0 and C24:0 were associated with lower TGF-β1 concentrations, and higher C16:0 were associated with higher TNF-α concentrations. We further examined effects of the aging FA profile on monocyte polarization and metabolism in THP1 monocytes. Monocytes preincubated with C16:0 increased secretion of pro-inflammatory cytokines in response to phorbol myristate acetate-induced differentiation through ceramide-dependent inhibition of PPARγ activity. Conversely, C18:1 primed a pro-resolving macrophage which was PPARγ dependent and ceramide dependent and which required oxidative phosphorylation. These data suggest that a midlife adult FA profile impairs the switch from proinflammatory to lower energy, requiring anti-inflammatory macrophages through metabolic reprogramming.

Age-associated changes in long-chain fatty acid profile during healthy aging promote pro-inflammatory monocyte polarization via PPARγ

Differences in lipid metabolism associate with age-related disease development and lifespan. Inflammation is a common link between metabolic dysregulation and aging. Saturated fatty acids (FAs) initiate pro-inflammatory signalling from many cells including monocytes; however, no existing studies have quantified age-associated changes in individual FAs in relation to inflammatory phenotype. Therefore, we have determined the plasma concentrations of distinct FAs by gas chromatography in 26 healthy younger individuals (age < 30 years) and 21 healthy FA individuals (age > 50 years). Linear mixed models were used to explore the association between circulating FAs, age and cytokines. We showed that plasma saturated, poly- and mono-unsaturated FAs increase with age. Circulating TNF-α and IL-6 concentrations increased with age, whereas IL-10 and TGF-β1 concentrations decreased. Oxidation of MitoSOX Red was higher in leucocytes from FA adults, and plasma oxidized glutathione concentrations were higher. There was significant colinearity between plasma saturated FAs, indicative of their metabolic relationships. Higher levels of the saturated FAs C18:0 and C24:0 were associated with lower TGF-β1 concentrations, and higher C16:0 were associated with higher TNF-α concentrations. We further examined effects of the aging FA profile on monocyte polarization and metabolism in THP1 monocytes. Monocytes preincubated with C16:0 increased secretion of pro-inflammatory cytokines in response to phorbol myristate acetate-induced differentiation through ceramide-dependent inhibition of PPARγ activity. Conversely, C18:1 primed a pro-resolving macrophage which was PPARγ dependent and ceramide dependent and which required oxidative phosphorylation. These data suggest that a midlife adult FA profile impairs the switch from proinflammatory to lower energy, requiring anti-inflammatory macrophages through metabolic reprogramming.

Age differences in associative and strategic processes in human conditional learning

Research indicates associative and strategic deficits mediate age related deficits in memory, whereas simple associative processes are independent of strategic processing and strategic processes mediate resistance to interference. The present study showed age-related deficits in a contingency learning task, although older participants' resistance to interference was not disproportionately affected. Recognition memory predicted discrimination, whereas general cognitive ability predicted resistance to interference, suggesting differentiation between associative and strategic processes in learning and memory, and age declines in associative processes. Older participants' generalisation of associative strength from existing to novel stimulus-response associations was consistent with elemental learning theories, whereas configural models predicted younger participants' responses. This is consistent with associative deficits and reliance on item-level representations in memory during later life. © 2011 Psychology Press Ltd.

Mobility changes in older age: neuropsychological, neurophysiological and cognitive predictors of successful adaptation in a real world scenario

The aims of this thesis were to investigate the neuropsychological, neurophysiological, and cognitive contributors to mobility changes with increasing age. In a series of studies with adults aged 45-88 years, unsafe pedestrian behaviour and falls were investigated in relation to i) cognitive functions (including response time variability, executive function, and visual attention tests), ii) mobility assessments (including gait and balance and using motion capture cameras), iii) motor initiation and pedestrian road crossing behavior (using a simulated pedestrian road scene), iv) neuronal and functional brain changes (using a computer based crossing task with magnetoencephalography), and v) quality of life questionnaires (including fear of falling and restricted range of travel). Older adults are more likely to be fatally injured at the far-side of the road compared to the near-side of the road, however, the underlying mobility and cognitive processes related to lane-specific (i.e. near-side or far-side) pedestrian crossing errors in older adults is currently unknown. The first study explored cognitive, motor initiation, and mobility predictors of unsafe pedestrian crossing behaviours. The purpose of the first study (Chapter 2) was to determine whether collisions at the near-side and far-side would be differentially predicted by mobility indices (such as walking speed and postural sway), motor initiation, and cognitive function (including spatial planning, visual attention, and within participant variability) with increasing age. The results suggest that near-side unsafe pedestrian crossing errors are related to processing speed, whereas far-side errors are related to spatial planning difficulties. Both near-side and far-side crossing errors were related to walking speed and motor initiation measures (specifically motor initiation variability). The salient mobility predictors of unsafe pedestrian crossings determined in the above study were examined in Chapter 3 in conjunction with the presence of a history of falls. The purpose of this study was to determine the extent to which walking speed (indicated as a salient predictor of unsafe crossings and start-up delay in Chapter 2), and previous falls can be predicted and explained by age-related changes in mobility and cognitive function changes (specifically within participant variability and spatial ability). 53.2% of walking speed variance was found to be predicted by self-rated mobility score, sit-to-stand time, motor initiation, and within participant variability. Although a significant model was not found to predict fall history variance, postural sway and attentional set shifting ability was found to be strongly related to the occurrence of falls within the last year. Next in Chapter 4, unsafe pedestrian crossing behaviour and pedestrian predictors (both mobility and cognitive measures) from Chapter 2 were explored in terms of increasing hemispheric laterality of attentional functions and inter-hemispheric oscillatory beta power changes associated with increasing age. Elevated beta (15-35 Hz) power in the motor cortex prior to movement, and reduced beta power post-movement has been linked to age-related changes in mobility. In addition, increasing recruitment of both hemispheres has been shown to occur and be beneficial to perform similarly to younger adults in cognitive tasks (Cabeza, Anderson, Locantore, & McIntosh, 2002). It has been hypothesised that changes in hemispheric neural beta power may explain the presence of more pedestrian errors at the farside of the road in older adults. The purpose of the study was to determine whether changes in age-related cortical oscillatory beta power and hemispheric laterality are linked to unsafe pedestrian behaviour in older adults. Results indicated that pedestrian errors at the near-side are linked to hemispheric bilateralisation, and neural overcompensation post-movement, 4 whereas far-side unsafe errors are linked to not employing neural compensation methods (hemispheric bilateralisation). Finally, in Chapter 5, fear of falling, life space mobility, and quality of life in old age were examined to determine their relationships with cognition, mobility (including fall history and pedestrian behaviour), and motor initiation. In addition to death and injury, mobility decline (such as pedestrian errors in Chapter 2, and falls in Chapter 3) and cognition can negatively affect quality of life and result in activity avoidance. Further, number of falls in Chapter 3 was not significantly linked to mobility and cognition alone, and may be further explained by a fear of falling. The objective of the above study (Study 2, Chapter 3) was to determine the role of mobility and cognition on fear of falling and life space mobility, and the impact on quality of life measures. Results indicated that missing safe pedestrian crossing gaps (potentially indicating crossing anxiety) and mobility decline were consistent predictors of fear of falling, reduced life space mobility, and quality of life variance. Social community (total number of close family and friends) was also linked to life space mobility and quality of life. Lower cognitive functions (particularly processing speed and reaction time) were found to predict variance in fear of falling and quality of life in old age. Overall, the findings indicated that mobility decline (particularly walking speed or walking difficulty), processing speed, and intra-individual variability in attention (including motor initiation variability) are salient predictors of participant safety (mainly pedestrian crossing errors) and wellbeing with increasing age. More research is required to produce a significant model to explain the number of falls.

Perceivers' impressions of self -presentation tactics: The effects of age and gender

Eighty-four young and 84 older men and women participants, read scenarios in which a male or female target uses either a self-enhancement or a self-deprecation tactic to present him/herself in front of either a close friend or a new acquaintance. Then participants i.e., perceivers) rated their impressions of the self-enhancing or self-deprecating target on six scales: likable, self-knowledgeable, honest, depressed, happy, and anxious. Overall, both young and old perceivers gave more favorable ratings to self-enhancing targets than to self-deprecating targets. Both young and old perceivers' impressions did not differ for a target who presented him/herself in front of a friend or in front of an acquaintance. Also, perceivers completed Singelis' (1994) Self-Construal Measurement, which measures both interdependent and independent self-construals. As predicted, older perceivers had a higher level of interdependent self-construal than did young perceivers. Unexpectedly, female perceivers had a higher level of independent self-construal than did male perceivers. Neither the age-related nor gender-related differences in self-construals were associated with any age-related or gender-related differences in perceivers' impressions of the self-enhancing and self-deprecating targets. That is, the moderator effects of self-construals on the relationships between self-presentation tactic conditions and ratings of targets were not-significant. ^

The role of age and emotional valence in word recognition: an ex-Gaussian analysis

The aim of this work is to evaluate the roles of age and emotional valence in word recognition in terms of ex-Gaussian distribution components. In order to do that, a word recognition task was carried out with two age groups, in which emotional valence was manipulated. Older participants did not present a clear trend for reaction times. The younger participants showed significant statistical differences in negative words for target and distracting conditions. Addressing the ex-Gaussian tau parameter, often related to attentional demands in the literature, age-related differences in emotional valence seem not to have an effect for negative words. Focusing on emotional valence for each group, the younger participants only showed an effect on negative distracting words. The older participants showed an effect regarding negative and positive target words, and negative distracting words. This suggests that the attentional demand is higher for emotional words, in particular, for the older participants.

Age and gender differences in the relation between self-concept facets and self-esteem

This study tested whether the gender intensification hypothesis applies to relations between multiple domain-specific self-concept facets and self-esteem. This hypothesis predicts gender-stereotypic differences in these relations and assumes they intensify with age. Furthermore, knowledge about gender-related or age-related differences in self-concept-self-esteem relations might provide valuable knowledge for designing effective self-esteem enhancement interventions. We investigated grade and gender differences in the relations between domain-specific self-concept facets and self-esteem within a sample of 1958 German students in Grades 3 to 6. Results indicated no difference in the self-concept - self-esteem relations between the subsamples of third and fourth graders and fifth and sixth graders or between boys and girls. These relations also did not differ between boys and girls in the subsamples of third and fourth graders and fifth and sixth graders. These results suggest self-concept-self-esteem relations to be invariant across grade levels and gender and thus did not support the gender intensification hypothesis.