Epigenetic alterations in longevity regulators, reduced life span, and exacerbated aging-related pathology in old father offspring mice.

Advanced age is not only a major risk factor for a range of disorders within an aging individual but may also enhance susceptibility for disease in the next generation. In humans, advanced paternal age has been associated with increased risk for a number of diseases. Experiments in rodent models have provided initial evidence that paternal age can influence behavioral traits in offspring animals, but the overall scope and extent of paternal age effects on health and disease across the life span remain underexplored. Here, we report that old father offspring mice showed a reduced life span and an exacerbated development of aging traits compared with young father offspring mice. Genome-wide epigenetic analyses of sperm from aging males and old father offspring tissue identified differentially methylated promoters, enriched for genes involved in the regulation of evolutionarily conserved longevity pathways. Gene expression analyses, biochemical experiments, and functional studies revealed evidence for an overactive mTORC1 signaling pathway in old father offspring mice. Pharmacological mTOR inhibition during the course of normal aging ameliorated many of the aging traits that were exacerbated in old father offspring mice. These findings raise the possibility that inherited alterations in longevity pathways contribute to intergenerational effects of aging in old father offspring mice.

Experience of an upper limb training program with a non-immersive virtual reality system in patients after stroke: a qualitative study.

OBJECTIVES: The YouGrabber (YG) is a new virtual reality training system that focuses on unilateral and bimanual activities. This nested study was part of a larger multicenter randomized controlled trial and explored experiences of people with chronic stroke during a 4 weeks intensive upper limb training with YG. DESIGN: A qualitative design using semi-structured, face-to-face interviews. A phenomenological descriptive approach was used, with data coded, categorized and summarized using a thematic analysis. Topics investigated included: the experience of YG training, perceived impact of YG training on arm function, and the role of the treating therapist. RESULTS: Five people were interviewed (one female, age range 55 to 75 years, 1 to 6 years poststroke). Seven main themes were identified: (1) general experience, (2) expectations, (3) feedback, (4) arm function, (5) physiotherapist's role, (6) fatigue, (7) motivation. Key experiences reported included feelings of motivation and satisfaction, with positive factors identified as challenge, competition, fun and effort. The YG training appeared to trigger greater effort, however fatigue was experienced at the end of the training. Overall, patients described positive changes in upper limb motor function and activity level, e.g. automatic arm use. While the opportunity for self-practice was appreciated, input from the therapist at the start of the intervention was deemed important for safety and confidence. CONCLUSIONS: Reported experiences were mostly positive and the participants were motivated to practice intensively. They enjoyed the challenging component of the games.

Standardized, comprehensive, hospital-based circuit training in people with multiple sclerosis: results on feasibility, adherence and satisfaction of the training intervention.

BACKGROUND: We developed a standardized, comprehensive, ambulatory, hospital-based neurorehabilitation program ("MS-Fit") to improve disability, activities of daily living and quality of life in people with multiple sclerosis (PwMS). AIM: The aim of this study was to assess feasibility, adherence and satisfaction of the training intervention. DESIGN: Prospective multicenter cohort study analysis. SETTING: Ambulatory, hospital-based study. POPULATION: PwMS, aged 18 to 75 years, complaining about multiple sclerosis-related disability affecting activities of daily living and/or quality of life. METHODS: A standardized, ambulatory, hospital-based circuit training consisting of six workstations (aerobic exercise training, strength upper limbs, balance, manual dexterity, reactivity, strength and flexibility lower limbs) was performed two hours, twice weekly, for two months in groups of two to six participants supervised by experienced physiotherapists. Physiotherapists adapted the type and intensity of training according to the participants' individual performance using a training booklet. Program satisfaction and adherence were evaluated using a questionnaire and the attendance rate (clinicaltrials.gov Identifier: NCT02440516). RESULTS: Fifty-five participants started (mean age 52.82 years±10.68 standard deviation, range 29-74; 69% female; median Expanded Disability Status Scale 3.5, range 1.0-7.0) and 49 (89%) finished the training program. Main reasons to drop out during the training were lack of time, travel problems, social issues or Uthoff's phenomenon during the summer. All participants finalizing the training achieved >80% (mean 92.26%, ±7.59) attendance rate and sent back the questionnaire. Overall participant's satisfaction was high with a median of 9 points (range 4-10) on a Likert Scale from 0-10. Program quality was rated "good" with an overall median score of 39/50 points (range 26-50) and 95% of the participants would recommend the program to others. CONCLUSIONS: MS-Fit is a feasible training program with high patient satisfaction and adherence. It enables high intensity ambulatory training and can be easily reproduced due to its standardized nature. CLINICAL REHABILITATION IMPACT: MS-FIT enables a standardized ambulatory high intensity training that is easily reproducible. Participants benefit from group training and from individual adaption of the training through professional supervision.

Effect of a four-week virtual reality-based training versus conventional therapy on upper limb motor function after stroke: A multicenter parallel group randomized trial.

BACKGROUND: Virtual reality-based training has found increasing use in neurorehabilitation to improve upper limb training and facilitate motor recovery. OBJECTIVE: The aim of this study was to directly compare virtual reality-based training with conventional therapy. METHODS: In a multi-center, parallel-group randomized controlled trial, patients at least 6 months after stroke onset were allocated either to an experimental group (virtual reality-based training) or a control group receiving conventional therapy (16x45 minutes within 4 weeks). The virtual reality-based training system replicated patients´ upper limb movements in real-time to manipulate virtual objects. Blinded assessors tested patients twice before, once during, and twice after the intervention up to 2-month follow-up for dexterity (primary outcome: Box and Block Test), bimanual upper limb function (Chedoke-McMaster Arm and Hand Activity Inventory), and subjective perceived changes (Stroke Impact Scale). RESULTS: 54 eligible patients (70 screened) participated (15 females, mean age 61.3 years, range 20-81 years, time since stroke 3.0±SD 3 years). 22 patients were allocated to the experimental group and 32 to the control group (3 drop-outs). Patients in the experimental and control group improved: Box and Block Test mean 21.5±SD 16 baseline to mean 24.1±SD 17 follow-up; Chedoke-McMaster Arm and Hand Activity Inventory mean 66.0±SD 21 baseline to mean 70.2±SD 19 follow-up. An intention-to-treat analysis found no between-group differences. CONCLUSIONS: Patients in the experimental and control group showed similar effects, with most improvements occurring in the first two weeks and persisting until the end of the two-month follow-up period. The study population had moderate to severely impaired motor function at entry (Box and Block Test mean 21.5±SD 16). Patients, who were less impaired (Box and Block Test range 18 to 72) showed higher improvements in favor of the experimental group. This result could suggest that virtual reality-based training might be more applicable for such patients than for more severely impaired patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT01774669.

Every-other-day feeding extends lifespan but fails to delay many symptoms of aging in mice.

Dietary restriction regimes extend lifespan in various animal models. Here we show that longevity in male C57BL/6J mice subjected to every-other-day feeding is associated with a delayed onset of neoplastic disease that naturally limits lifespan in these animals. We compare more than 200 phenotypes in over 20 tissues in aged animals fed with a lifelong every-other-day feeding or ad libitum access to food diet to determine whether molecular, cellular, physiological and histopathological aging features develop more slowly in every-other-day feeding mice than in controls. We also analyze the effects of every-other-day feeding on young mice on shorter-term every-other-day feeding or ad libitum to account for possible aging-independent restriction effects. Our large-scale analysis reveals overall only limited evidence for a retardation of the aging rate in every-other-day feeding mice. The data indicate that every-other-day feeding-induced longevity is sufficiently explained by delays in life-limiting neoplastic disorders and is not associated with a more general slowing of the aging process in mice.Dietary restriction can extend the life of various model organisms. Here, Xie et al. show that intermittent periods of fasting achieved through every-other-day feeding protect mice against neoplastic disease but do not broadly delay organismal aging in animals.

Using mixed methods to evaluate efficacy and user expectations of a virtual reality-based training system for upper-limb recovery in patients after stroke: a study protocol for a randomised controlled trial.

BACKGROUND: In recent years, virtual reality has been introduced to neurorehabilitation, in particular with the intention of improving upper-limb training options and facilitating motor function recovery. METHODS/DESIGN: The proposed study incorporates a quantitative part and a qualitative part, termed a mixed-methods approach: (1) a quantitative investigation of the efficacy of virtual reality training compared to conventional therapy in upper-limb motor function are investigated, (2a) a qualitative investigation of patients' experiences and expectations of virtual reality training and (2b) a qualitative investigation of therapists' experiences using the virtual reality training system in the therapy setting. At three participating clinics, 60 patients at least 6 months after stroke onset will be randomly allocated to an experimental virtual reality group (EG) or to a control group that will receive conventional physiotherapy or occupational therapy (16 sessions, 45 minutes each, over the course of 4 weeks). Using custom data gloves, patients' finger and arm movements will be displayed in real time on a monitor, and they will move and manipulate objects in various virtual environments. A blinded assessor will test patients' motor and cognitive performance twice before, once during, and twice after the 4-week intervention. The primary outcome measure is the Box and Block Test. Secondary outcome measures are the Chedoke-McMaster Stroke Assessments (hand, arm and shoulder pain subscales), the Chedoke-McMaster Arm and Hand Activity Inventory, the Line Bisection Test, the Stroke Impact Scale, the MiniMentalState Examination and the Extended Barthel Index. Semistructured face-to-face interviews will be conducted with patients in the EG after intervention finalization with a focus on the patients' expectations and experiences regarding the virtual reality training. Therapists' perspectives on virtual reality training will be reviewed in three focus groups comprising four to six occupational therapists and physiotherapists. DISCUSSION: The interviews will help to gain a deeper understanding of the phenomena under investigation to provide sound recommendations for the implementation of the virtual reality training system for routine use in neurorehabilitation complementing the quantitative clinical assessments. TRIAL REGISTRATION: Cliniclatrials.gov Identifier: NCT01774669 (15 January 2013).