DNA methylation profiling of human chromosomes 6, 20 and 22.

DNA methylation is the most stable type of epigenetic modification modulating the transcriptional plasticity of mammalian genomes. Using bisulfite DNA sequencing, we report high-resolution methylation profiles of human chromosomes 6, 20 and 22, providing a resource of about 1.9 million CpG methylation values derived from 12 different tissues. Analysis of six annotation categories showed that evolutionarily conserved regions are the predominant sites for differential DNA methylation and that a core region surrounding the transcriptional start site is an informative surrogate for promoter methylation. We find that 17% of the 873 analyzed genes are differentially methylated in their 5' UTRs and that about one-third of the differentially methylated 5' UTRs are inversely correlated with transcription. Despite the fact that our study controlled for factors reported to affect DNA methylation such as sex and age, we did not find any significant attributable effects. Our data suggest DNA methylation to be ontogenetically more stable than previously thought.

Pilot study of a high-intensity interval training program in older adults: Safety, feasibility, functional fitness and cognitive effects.

Exercise can boost physical and cognitive health in older adults. However, there are a lack of accessible exercise programs that foster adherence among older adults. In this study, we aimed to establish the safety and feasibility of APEX, a new exercise program designed to optimize fitness and cognitive gains for older adults, in addition to evaluating its acute physiological effects, and assessing its possible effects on functional fitness and cognition among healthy older adults. APEX utilizes a multimodal progressive high-intensity interval training (HIIT) design, with high-intensity intervals focused on enhancing cardiovascular fitness and muscle strength, and recovery intervals that incorporate balance and mobility exercises. The APEX training was tested in healthy older adults (n=4) over the course of four weeks. Ultimately, APEX was found to be safe and feasible, with no adverse events and high adherence. Participants met heart rate targets for all of the high-intensity exercises, and all intervals had a significant difference in heart rates between high-intensity and recovery periods in linear effects models (p<0.001). Improvements in functional fitness were observed in aerobic endurance, lower body strength, and balance. The intervention was also associated with positive trends in the cognitive domains of information processing, working memory, executive control, and attention. APEX offers a promising alternative to traditional cardiovascular exercise modalities for older adults with additional benefits for functional fitness and cognition. These results encourage further testing of the APEX program in older adults and different clinical populations.

Feasibility of Virtually Delivering Functional Fitness Assessments and a Fitness Training Program in Community-Dwelling Older Adults.

The COVID-19 pandemic limited older adults' access to preventative and diagnostic services and negatively affected accessibility to age-appropriate exercise programs. The purpose of this study was to assess the feasibility of conducting guided virtual functional fitness assessments before and after participation in an 8-week virtual, live fitness program (Vivo) designed for older adults. It was hypothesized there would be no significant difference between in-person and virtual functional fitness assessments and function would improve following the program. Thirteen community-dwelling older adults were recruited, screened, and randomly assigned to in-person-first or virtual-first fitness assessment groups. Validated assessments were delivered using standardized scripts by trained researchers and included Short Physical Performance Battery (SPPB) balance, a 30 s Chair Stand Test, 8 Foot Up-and-Go Test, 30 s Arm Curl Test, and 2 min Step Test. The eight-week, twice-a-week live virtual fitness program involved cardiovascular, balance, agility, Dual-Task, and strength training. Results showed no significant differences between all but one assessment measures, and several measures improved following the eight-week program. Fidelity checks demonstrated the high fidelity of program delivery. These findings illustrate that virtual assessments can be a feasible method to measure functional fitness in community-dwelling older adults.

Integrated cognitive and physical fitness training enhances attention abilities in older adults.

Preserving attention abilities is of great concern to older adults who are motivated to maintain their quality of life. Both cognitive and physical fitness interventions have been utilized in intervention studies to assess maintenance and enhancement of attention abilities in seniors, and a coupling of these approaches is a compelling strategy to buttress both cognitive and physical health in a time- and resource-effective manner. With this perspective, we created a closed-loop, motion-capture video game (Body-Brain Trainer: BBT) that adapts a player's cognitive and physical demands in an integrated approach, thus creating a personalized and cohesive experience across both domains. Older adults who engaged in two months of BBT improved on both physical fitness (measures of blood pressure and balance) and attention (behavioral and neural metrics of attention on a continuous performance task) outcome measures beyond that of an expectancy matched, active, placebo control group, with maintenance of improved attention performance evidenced 1 year later. Following training, the BBT group's improvement on the attention outcome measure exceeded performance levels attained by an untrained group of 20-year olds, and showed age-equilibration of a neural signature of attention shown to decline with age: midline frontal theta power. These findings highlight the potential benefits of an integrated, cognitive-physical, closed-loop training platform as a powerful tool for both cognitive and physical enhancement in older adults.

The VMAT-2 inhibitor tetrabenazine alters effort-related decision making as measured by the T-maze barrier choice task: reversal with the adenosine A2A antagonist MSX-3 and the catecholamine uptake blocker bupropion.

RATIONALE: Depressed people show effort-related motivational symptoms, such as anergia, retardation, lassitude, and fatigue. Animal tests can model these motivational symptoms, and the present studies characterized the effort-related effects of the vesicular monoamine transport (VMAT-2) inhibitor tetrabenazine. Tetrabenazine produces depressive symptoms in humans and, at low doses, preferentially depletes dopamine. OBJECTIVES: The current studies investigated the effects of tetrabenazine on effort-based decision making using the T-maze barrier task. METHODS: Rats were tested in a T-maze in which the choice arms of the maze contain different reinforcement densities, and under some conditions, a vertical barrier was placed in the high-density arm to provide an effort-related challenge. The first experiment assessed the effects of tetrabenazine under different maze conditions: a barrier in the arm with 4 food pellets and 2 pellets in the no barrier arm (4-2 barrier), 4 pellets in one arm and 2 pellets in the other with no barrier in either arm (no barrier), and 4 pellets in the barrier arm with no pellets in the other (4-0 barrier). RESULTS: Tetrabenazine (0.25-0.75 mg/kg IP) decreased selection of the high cost/high reward arm when the barrier was present, but had no effect on choice under the no barrier and 4-0 barrier conditions. The effects of tetrabenazine on barrier climbing in the 4-2 condition were reversed by the adenosine A2A antagonist MSX-3 and the catecholamine uptake inhibitor and antidepressant bupropion. CONCLUSIONS: These studies have implications for the development of animal models of the motivational symptoms of depression and other disorders.

Exploring the health of women with mobility impairments.

This study examined health surveys of 109 midwestern women (mean age 44.6 +/- 8.2 years) with impaired mobility to determine whether mobility impairment severity was related to self-reported health, health care use, and engaging in health behaviors. The study also assessed which health factors were associated with pain. Women with severe mobility impairments reported poorer physical functioning, but better mental health than less severely impaired women after controlling for age, disability duration, and/or bodily pain. Degree of mobility impairment level was not significantly related to health behaviors, except having a checkup in the past year; more moderately impaired women reported these visits than mildly impaired women. Furthermore, pain was significantly associated with social functioning, general health, and secondary conditions. The findings suggest that factors beyond impairment level, such as pain, age, and disability duration, are related to the health of mobility-impaired women.

Functional training improves club head speed and functional fitness in older golfers.

Functional training programs have been used in a variety of rehabilitation settings with documented success. Based on that success, the concept of functional training has gained popularity in applied fitness settings to enhance sport performance. However, there has been little or no research studying the efficacy of functional training programs on the improvement of sport performance or functional fitness. Thus, it was the purpose of this study to determine the effect of a progressive functional training program on club head speed and functional fitness in older male golfers. Eighteen male golfers (age: 70.7 +/- 9.1 [SD] years) were randomly assigned to an exercise (N = 11) or control (N = 7) group. The exercise group participated in an 8-week progressive functional training program including flexibility exercises, core stability exercises, balance exercises, and resistance exercises. Pre- and postmeasurements included club head speed of a driver by radar (exercise and Control) and Fullerton Senior Fitness Test measurements (exercise only). One-way analysis of covariance was performed on club head speed measurements using pretest measurements as the covariate. Paired t-tests were performed to analyze Senior Fitness Test variables. After the intervention, maximal club head speed increased in the exercise group (127.3 +/- 13.4 to 133.6 +/- 14.2 km x hr(-1)) compared with the control group (134.5 +/- 14.6 to 133.3 +/- 11.2 km x hr(-1); p < 0.05). Additionally, improvements (p < 0.05) were detected for most Senior Fitness Test variables in the exercise group. In summary, this functional training program resulted in significant improvements in club head speed and several components of functional fitness. Future research should continue to examine the effect of functional training programs on sport performance and functional fitness in older adults.

Effects of an 8-week multimodal exercise program on strength, flexibility, and golf performance in 55- to 79-year-old men.

Substantial research has indicated the beneficial effect of physical activity on physical fitness and activities of daily living in older adults, but none have investigated the effects on performance of recreational activities. This investigation studied the effect of an exercise program on fitness and golf-clubhead speed in older men. Thirty-one golfers (mean age 65.1 +/- 6.2 years) were randomly assigned to a treatment (n = 19) or control (n = 12) group. The treatment group completed an 8-week strength and flexibility program. Assessments included 10-RM muscle strength; selected range-of-motion (ROM) measurements; and golf-clubhead speed (CHS). ANCOVA revealed significant differences between groups (p <.005) for all strength measurements and several ROM measurements. CHS was significantly different (p <.05) between groups after the intervention. Mean CHS improved from 85.0 to 87.1 miles/hr (136.8 to 140.2 km/hr). These results indicate that a strength and flexibility program can improve golf performance in older adults.