Aerobic Exercise for the Promotion of Healthy Aging: Changes in Brain Structure Assessed with New Methods

As the proportion of older individuals in the population increases, so does the scientific concern surrounding age-related deterioration of brain tissue and related cognitive decline. One modifiable lifestyle factor of interest in the pursuit to slow or even reverse age-related brain atrophy is aerobic exercise. A number of studies have already demonstrated that aerobic exercise in older age can induce maintenance (i.e., reduction of loss) of both gray and white matter volume, particularly in the frontal regions of the brain, which are vulnerable to shrinkage in older age. Other magnetic resonance imaging (MRI)-based techniques, such as quantitative MRI and diffusion-weighted MRI, have been used to measure age-related deterioration of gray and white matter integrity in both voxel-wise analyses as well as on the latent level, but whether these negative changes can be ameliorated through exercise has yet to be shown. The current dissertation includes three papers which used a number of both established and novel MRI-based metrics to quantify changes in brain tissue integrity resulting from aging, as well as to investigate whether these changes can be ameliorated through aerobic exercise. In Paper I (Wenger et al., 2022), we tested the reliability of quantitative MRI measures, namely longitudinal relaxation rate, effective transverse relaxation rate, proton density, and magnetization transfer saturation, by measuring them in a two-day, four-session design with repositioning in the scanner. Using the intra-class effect decomposition model, we found that magnetization transfer saturation could reliably detect individual differences, validating its use to investigate changes in brain structure longitudinally, as well as correlations with other variables of interest, such as change in cardiovascular fitness. In Paper II (Polk et al., 2022), we tested the effects of aerobic exercise on a latent factor of gray-matter structural integrity, comprising observed measures of gray-matter volume, magnetization transfer saturation, and mean diffusivity, in regions of interest that have previously shown volumetric effects of aerobic exercise. We found that gray-matter structural integrity was maintained in frontal and midline regions, and that change in gray-matter structural integrity in the right anterior cingulate cortex was positively correlated with change in cardiovascular fitness within exercising participants. These results suggest a causal relationship between aerobic exercise, cardiovascular fitness, and gray-matter structural integrity in this region. In Paper III (Polk et al., 2022), we tested the effects of aerobic exercise on white matter integrity, measured with both established and recently developed metrics. We were able to replicate findings from a previous study on the effects of aerobic exercise on white matter volume, and we also found change-change correlations between white matter volume and cardiovascular fitness as well as between white matter volume and performance on a test of perceptual speed. We also found unexpected exercise-induced changes in the diffusion weighted imaging-derived metrics of fractional anisotropy, mean diffusivity, fiber density, and fiber density and cross-section. Specifically, we found increases (or decreases in the case of mean diffusivity) within control participants and decreases (or increases in mean diffusivity) in exercisers. Furthermore, we found that percent change in fiber density and fiber density and cross-section correlated negatively with percent change in both cardiovascular fitness and cognitive performance. This casts doubt on the functional interpretation of these measures and suggests that the “more is better” principle may not be universally applicable when investigating age-related and exercise-induced changes in white matter integrity. In sum, this dissertation showed that regular at-home aerobic exercise, which may be more accessible for older individuals than supervised exercise, can be an effective tool to ameliorate age-related decreases in a latent measure of gray-matter structural integrity as well as white matter volume. It also illuminated potential limitations of other measures of white matter integrity in the context of aging and aerobic exercise, and calls for further research into these novel measures, especially when considering functional outcomes such as cognitive performance

No Evidence for a Boost in Psychosocial Functioning in Older Age After a 6-Months Physical Exercise Intervention

The beneficial effects of physical exercise on physical health and cognitive functioning have been repeatedly shown. However, evidence of its effect on psychosocial functioning in healthy adults is still scarce or inconclusive. One limitation of many studies examining this link is their reliance on correlational approaches or specific subpopulations, such as clinical populations. The present study investigated the effects of a physical exercise intervention on key factors of psychosocial functioning, specifically well-being, stress, loneliness, and future time perspective. We used data from healthy, previously sedentary older adults (N = 132) who participated in a 6-month at-home intervention, either engaging in aerobic exercise or as part of a control group who participated in foreign language-learning or reading of selected native-language literature. Before and after the intervention, comprehensive cardiovascular pulmonary testing and a psychosocial questionnaire were administered. The exercise group showed significantly increased fitness compared to the control group. Contrary to expectations, however, we did not find evidence for a beneficial effect of this fitness improvement on any of the four domains of psychosocial functioning we assessed. This may be due to pronounced stability of such psychological traits in older age, especially in older adults who show high levels of well-being initially. Alternatively, it may be that the well-documented beneficial effects of physical exercise on brain structure and function, as well as cognition differ markedly from beneficial effects on psychosocial functioning. While aerobic exercise may be the driving factor for the former, positive effects on the latter may only be invoked by other aspects of exercise, for example, experiences of mastery or a feeling of community.Peer Reviewe

Aerobic exercise is associated with region-specific changes in volumetric, tensor-based, and fixel-based measures of white matter integrity in healthy older adults

White matter integrity and cognition have been found to decline with advancing adult age. Aerobic exercise may be effective in counteracting these declines. Generally, white matter integrity has been quantified using a volumetric measure (WMV) and with tensor-based parameters, such as fractional anisotropy (FA) and mean diffusivity (MD), the validity of which appears to be compromised in the presence of crossing fibers. Fixel-based analysis techniques claim to overcome this problem by yielding estimates of fiber density (FD), cross-section (FC), and their product (FDC) in multiple directions per voxel. In a sample of 61 healthy older adults (63–76 years old), we quantified changes in white matter integrity following an aerobic exercise intervention with the commonly used volumetric and tensor-based metrics (WMV, FA, MD) and with fixel-based metrics (FD, FC, FDC). We investigated the associations of changes in these white matter parameters with changes in cardiovascular fitness and Digit Symbol Substitution task (DSST) performance, a marker of perceptual speed. In line with previous findings, we observed maintained WMV in the corpus callosum of exercisers, and positive change-change correlations between WMV and fitness, and between WMV and perceptual speed. For FA and MD, group differences in change opposite to those hypothesized were found in the corpus callosum, posterior corona radiata, and superior longitudinal fasciculus at an uncorrected significance threshold. Likewise, regions in superficial WM in the prefrontal cortex showed group differences in FD and FDC change, uncorrected, with more positive change in controls and more negative change in exercisers. Finally, changes in FD and FDC were found to be inversely correlated to changes in fitness and DSST performance. The present results corroborate previous findings of WMV changes, but cast doubt on current physiological interpretations of both tensor-based and fixel-based indicators of white matter properties in the context of exercise intervention studies

\u3ci\u3eDrosophila\u3c/i\u3e Muller F Elements Maintain a Distinct Set of Genomic Properties Over 40 Million Years of Evolution

The Muller F element (4.2 Mb, ~80 protein-coding genes) is an unusual autosome of Drosophila melanogaster; it is mostly heterochromatic with a low recombination rate. To investigate how these properties impact the evolution of repeats and genes, we manually improved the sequence and annotated the genes on the D. erecta, D. mojavensis, and D. grimshawi F elements and euchromatic domains from the Muller D element. We find that F elements have greater transposon density (25–50%) than euchromatic reference regions (3–11%). Among the F elements, D. grimshawi has the lowest transposon density (particularly DINE-1: 2% vs. 11–27%). F element genes have larger coding spans, more coding exons, larger introns, and lower codon bias. Comparison of the Effective Number of Codons with the Codon Adaptation Index shows that, in contrast to the other species, codon bias in D. grimshawi F element genes can be attributed primarily to selection instead of mutational biases, suggesting that density and types of transposons affect the degree of local heterochromatin formation. F element genes have lower estimated DNA melting temperatures than D element genes, potentially facilitating transcription through heterochromatin. Most F element genes (~90%) have remained on that element, but the F element has smaller syntenic blocks than genome averages (3.4–3.6 vs. 8.4–8.8 genes per block), indicating greater rates of inversion despite lower rates of recombination. Overall, the F element has maintained characteristics that are distinct from other autosomes in the Drosophila lineage, illuminating the constraints imposed by a heterochromatic milieu