The Effectiveness of Exercise Interventions for the Management of Frailty: A Systematic Review

This systematic review examines the effectiveness of current exercise interventions for the management of frailty. Eight electronic databases were searched for randomized controlled trials that identified their participants as “frail” either in the title, abstract, and/or text and included exercise as an independent component of the intervention. Three of the 47 included studies utilized a validated definition of frailty to categorize participants. Emerging evidence suggests that exercise has a positive impact on some physical determinants and on all functional ability outcomes reported in this systematic review. Exercise programs that optimize the health of frail older adults seem to be different from those recommended for healthy older adults. There was a paucity of evidence to characterize the most beneficial exercise program for this population. However, multicomponent training interventions, of long duration (≥5 months), performed three times per week, for 30–45 minutes per session, generally had superior outcomes than other exercise programs. In conclusion, structured exercise training seems to have a positive impact on frail older adults and may be used for the management of frailty

Mitochondrial dysfunction and mitophagy defects in LRRK2-R1441C Parkinson's disease models

Mutations in the Leucine-Rich Repeat Kinase 2 (LRRK2) gene have been identified as one of the most common genetic causes of Parkinson’s disease (PD). The LRRK2 PD-associated mutations LRRK2G2019S and LRRK2R1441C, located in the kinase domain and in the ROC-COR domain, respectively, have been demonstrated to impair mitochondrial function. Here, we sought to further our understanding of mitochondrial health and mitophagy by integrating data from LRRK2R1441C rat primary cortical and human induced pluripotent stem cell-derived dopamine (iPSC-DA) neuronal cultures as models of PD. We found that LRRK2R1441C neurons exhibit decreased mitochondrial membrane potential, impaired mitochondrial function and decreased basal mitophagy levels. Mitochondrial morphology was altered in LRRK2R1441C iPSC-DA but not in cortical neuronal cultures or aged striatal tissue, indicating a cell-type-specific phenotype. Additionally, LRRK2R1441C but not LRRK2G2019S neurons demonstrated decreased levels of the mitophagy marker pS65Ub in response to mitochondrial damage, which could disrupt degradation of damaged mitochondria. This impaired mitophagy activation and mitochondrial function were not corrected by the LRRK2 inhibitor MLi-2 in LRRK2R1441C iPSC-DA neuronal cultures. Furthermore, we demonstrate LRRK2 interaction with MIRO1, a protein necessary to stabilize and to anchor mitochondria for transport, occurs at mitochondria, in a genotype-independent manner. Despite this, we found that degradation of MIRO1 was impaired in LRRK2R1441C cultures upon induced mitochondrial damage, suggesting a divergent mechanism from the LRRK2G2019S mutation

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This systematic review examines the effectiveness of current exercise interventions for the management of frailty. Eight electronic databases were searched for randomized controlled trials that identified their participants as "frail" either in the title, abstract, and/or text and included exercise as an independent component of the intervention. Three of the 47 included studies utilized a validated definition of frailty to categorize participants. Emerging evidence suggests that exercise has a positive impact on some physical determinants and on all functional ability outcomes reported in this systematic review. Exercise programs that optimize the health of frail older adults seem to be different from those recommended for healthy older adults. There was a paucity of evidence to characterize the most beneficial exercise program for this population. However, multicomponent training interventions, of long duration (≥5 months), performed three times per week, for 30-45 minutes per session, generally had superior outcomes than other exercise programs. In conclusion, structured exercise training seems to have a positive impact on frail older adults and may be used for the management of frailty

Comparison of bone mineral density between male masters runners and cyclists

Click on the link to access this abstract at the publisher's website.For maintenance of bone mass during adulthood, it is commonly recommended to participate in relatively high level weight-bearing exercise. Weight-bearing exercise includes aerobic activities such as jogging or activities that produce high ground reaction forces such as jumping. Cycling is a popular form of aerobic exercise for older adults due to the reduced impact on the weight-bearing joints. However, due to the unloaded nature of cycling, some data suggest that bone mineral density at clinically important sites is reduced in cyclists. PURPOSE: To compare areal bone mineral density (aBMD) of the lumbar spine and non-dominant proximal femur between male masters runners and male masters cyclists. METHODS: Eight male masters runners (mean ± SD, age: 58.9 ± 4.4 yrs, height: 175.3 ± 6.9 cm, weight: 75.1 ± 14.3 kg) and eight male masters cyclists (mean ± SD, age: 63.8 ± 5.9 yrs, height: 176.8 ± 5.8 cm, weight: 76.8 ± 8.3 kg) underwent a dual energy x-ray absorptiometry (DXA) scan for assessment of aBMD of the non-dominant proximal femur (total hip and femoral neck) and lumbar spine (L1-L4) as well as percent body fat (%BF), and bone free lean body mass (BFLM). Data were analyzed using Independent Samples t-tests with an alpha level of 0.05. RESULTS: There were no significant differences in age, height, or weight between groups. Compared to masters cyclists, masters runners did not show any significant differences in %BF (16.8 ± 3.6 vs. 16.0 ± 3.3%, p=0.679), BFLM(59.1 ± 9.1 vs. 61.2 ± 7.6, p=0.618), lumbar spine aBMD (1.041 ± 0.130 vs. 0.991 ± 0.062, p=0.346), total hip aBMD (0.989 ± 0.152 vs. 0.917 ± 0.079, p=0.257), or femoral neck aBMD (0.816 ± 0.111 vs. 0.730 ± 0.074, p=0.090). CONCLUSION: Our preliminary findings suggest that male masters cyclists and runners do not differ in aBMD. However, our current findings are likely influenced by the small sample size which will be addressed in the near future

Viruslike Particles Encapsidating Respiratory Syncytial Virus M and M2 Proteins Induce Robust T Cell Responses

Subunit vaccines provide a safe, focused alternative to conventional vaccines. However, these vaccines often require significant adjuvants and are particularly hard to target toward cytotoxic T lymphocyte (CTL) immunity. Viruslike particles (VLPs) provide biomaterial scaffolds with pathogen-like polyvalent structures making them useful platforms for biomimetic antigen delivery to the immune system. Encapsidation of antigens within VLPs has been shown to enhance antigen availability for CD8 T cell responses. Here, we examine the potential to generate complex responses to multiple subunit antigens localized within the same VLP particle. Two proteins of respiratory syncytial virus (RSV) with well-characterized CD8 T cell responses, the matrix (M) and matrix 2 (M2) proteins, were successfully coencapsidated within the P22 VLP. Upon intranasal administration in mice, the particles stimulated CD8 T cell memory responses against both antigens. In addition, vaccination elicited tissue-resident T cell populations. Upon subsequent RSV challenge, P22-M/M2-treated mice displayed significantly reduced lung viral titers. This demonstrates the utility of the P22 VLP in directing immune responses to multiple encapsidated viral antigens, demonstrating the potential of this technology to facilitate immunity to multiple targets simultaneously