Regulation of senescence traits by MAPKs

GeroScience - A phenotype of indefinite growth arrest acquired in response to sublethal damage, cellular senescence affects normal aging and age-related disease. Mitogen-activated protein kinases...     

Autophagy is required for performance adaptive response to resistance training and exercise-induced adult neurogenesis

Endurance training promotes exercise-induced adaptations in brain, like hippocampal adult neurogenesis and autophagy induction. However, resistance training effect on the autophagy response in the brain has not been much explored. Questions such as whether partial systemic autophagy or the length of training intervention affect this response deserve further attention. Therefore, 8-week-old male wild-type (Wt; n = 36) and systemic autophagy-deficient (atg4b^−/−, KO; n = 36) mice were randomly distributed in three training groups, resistance (R), endurance (E), and control (non-trained), and in two training periods, 2 or 14 weeks. R and E maximal tests were evaluated before and after the training period. Forty-eight hours after the end of training program, cerebral cortex, striatum, hippocampus, and cerebellum were extracted for the analysis of autophagy proteins (LC3B-I, LC3B-II, and p62). Additionally, hippocampal adult neurogenesis was determined by doublecortin-positive cells count (DCX+) in brain sections. Our results show that, in contrast to Wt, KO were unable to improve R after both trainings. Autophagy levels in brain areas may be modified by E training only in cerebral cortex of Wt trained for 14 weeks, and in KO trained for 2 weeks. DCX + in Wt increased in R and E after both periods of training, with R for 14 weeks more effective than E. Interestingly, no changes in DCX + were observed in KO after 2 weeks, being even undetectable after 14 weeks of intervention. Thus, autophagy is crucial for R performance and for exercise-induced adult neurogenesis.     

The effects of exergames on anxiety levels: A systematic review and meta-analysis

There are currently many different approaches to performing exergames and there is still no consensus as to whether exergames are able to reduce anxiety levels, as well as whether exergames provide greater reductions on anxiety levels when added to traditional forms of clinical interventions. Therefore, the aim of the present systematic review and meta-analysis was to access data from studies that evaluated the effects of exergames on anxiety levels in humans. PubMed, Scopus and Cochrane databases were searched up to 22 February 2019. Inclusion criteria were acute and chronic (short-term and long-term interventions) studies which evaluated the effects of exergames in anxiety levels as primary or secondary aim. Of the 1342 studies found, 17 and 10 were included in qualitative analyses and meta-analyses, respectively. The within-group analysis found that exergames (standardized mean difference [SMD]: −0.57 [95% Confidence interval (CI): −0.86 to −0.28], P < .001) and usual care (SMD: −0.21 [95% CI: −0.34 to −0.08], P = .002) resulted in significant improvements on anxiety levels. However, the between-group meta-analysis on the effects of control interventions vs exergames (SMD: 0.02 [95% CI: −0.55 to 0.60], P = .939) found no significant difference between groups in anxiety levels reductions. There was also no significant difference (SMD: −0.04 [95% CI: −0.32 to 0.25], P = .805) between usual care vs exergames plus usual care interventions in anxiety levels reductions. Although exergames demonstrated within-group improvements in anxiety levels across different clinical populations, it was not greater than the effects from non-exercise interventions. Also, given the paucity of studies, small sample sizes, different research designs, and different population investigated, the existing evidence is insufficient to support the advantages of usual care supplemented by exergame intervention over usual care standalone in anxiety levels reduction.     

Multimorbidity and Evidence Generation

Most people with a chronic disease actually have more than one, a condition known as multimorbidity. Despite this, the evidence base to prevent adverse disease outcomes has taken a disease-specific approach. Drawing on a conference, Improving Guidelines for Multimorbid Patients, the goal of this paper is to identify challenges to the generation of evidence to support the care of people with multimorbidity and to make recommendations for improvement. We identified three broad categories of challenges: 1) challenges to defining and measuring multimorbidity; 2) challenges related to the effects of multimorbidity on study design, implementation and analysis; and 3) challenges inherent in studying heterogeneity of treatment effects in patients with differing comorbid conditions. We propose a set of recommendations for consideration by investigators and others (reviewers, editors, funding agencies, policymaking organizations) involved in the creation of evidence for this common type of person that address each of these challenges. The recommendations reflect a general approach that emphasizes broader inclusion (recruitment and retention) of patients with multimorbidity, coupled with more rigorous efforts to measure comorbidity and comorbidity burden and the influence of multimorbidity on outcomes and the effects of therapy. More rigorous examination of heterogeneity of treatment effects requires careful attention to prioritizing the most important comorbid-related questions, and also requires studies that provide greater statistical power than conventional trials have provided. Relatively modest changes in the orientation of current research along these lines can be helpful in pointing to and partially addressing selected knowledge gaps. However, producing a robust evidence base to support patient-centered decision making in complex individuals with multimorbidity, exposed to many different combinations of potentially interacting factors that can modify the risks and benefits of therapies, is likely to require a clinical research enterprise fundamentally restructured to be more fully integrated with routine clinical practice.