Adherence to the physical activity guideline beyond the recommended minimum weekly amount: impacts on indicators of physical function in older adults

IntroductionThe extent to which additional health benefits of accumulating twice the minimum amount of time in moderate-to-vigorous physical activity (MVPA) affects indicators of physical function in older adults is unclear. Therefore, the aim of the present study was to assess indicators of physical function in older adults who accumulate at least 150 but less than 300 min/week of MVPA compared to those accumulating at least 300 min/week.MethodsIndicators of physical function, including handgrip strength, 5 times sit-to-stand test (5-STS), squat jump and 6-min walk test (6MWT) were assessed in a sample of 193 older men (n = 71, 67 ± 2 years), and women (n = 122, 67 ± 2 years), who all accumulated at least 150 weekly minutes of MVPA. Time in MVPA was assessed by accelerometry during 1 week and engagement in muscle strengthening activities (MSA) was assessed by self-report. Protein intake was assessed by a food-frequency-questionnaire. Participants were classified as physically active (≥150 but <300 min of MVPA per week) or as highly physically active (≥300 min of MVPA per week).ResultsFactorial analysis of variance revealed that older adults accumulating at least 300 min of MVPA per week had a significantly (p < 0.05) better 6MWT performance and overall physical function compared to the less active group. These findings remained significant after further adjustment for MSA, sex, waist circumference and protein intake. In contrast, no significant differences in indicators of muscle strength were observed between the two groups.DiscussionAdherence to twice the recommended minimum amount of weekly MVPA time is related to a better physical function, evidenced by a better walking performance compared to adherence to the minimum weekly amount of MVPA. This finding emphasizes the benefits of accumulating daily MVPA beyond the minimum recommended amount to optimize the ability to perform activities of daily living, thus reducing the burden of physical disability and related health-care costs

Physical activity, muscle mass and physical function in older adults

Ageing is accompanied by a decline in physical function, including loss of muscle mass and muscle strength, which leads to impaired ability to perform activities of daily living and loss of independence. Physical activity (PA) is currently viewed as a key lifestyle factor with potential to mitigate these age-related deteriorations. Therefore, public health organizations have issued guidelines about amounts and types of physical activity for health benefits, where reductions in daily time spent sedentary in favour of more time in aerobic-type moderate-to-vigorous PA (MVPA) are emphasized. In addition, regular engagement in musclestrengthening activities (MSA) are recommended to promote maintenance of muscle mass and strength in ageing populations. However, to what extent different amounts and types of PA impact on different indicators of physical function, including muscle mass and strength, remains currently unclear. Therefore, the overall aim of this thesis was to investigate the impact of PA behaviours on muscle mass and physical function in older adults. In study I, it was shown that regular engagement in exercise activities during middle age was associated with a significantly higher muscle mass and a better cardiorespiratory fitness at old age. In study II, replacement of daily sedentary time with PA of at least light intensity was associated with a significantly lower sarcopenia risk in older adults, with greater benefits above the moderate PA intensity. Study III revealed that engagement in MSA at least twice a week was linked to a significantly lower sarcopenia risk in older adults who already perform at least 150 weekly minutes of MVPA. Finally, study IV showed that older adults who accumulate at least 300 weekly minutes of MVPA have a significantly better overall physical function than those who accumulate at least 150 but less than 300 minutes of MVPA per week. Overall, the findings from this thesis highlight the importance of adherence to the aerobic-type MVPA guideline alongside recommended engagement in MSA for mitigating age-related decline in physical function in older adults. Notably, accumulation of MVPA time beyond the minimum recommended amount provides additional functional benefits

Maximal Sprints Within the Warm-up Does Not Affect Pacing or Performance in a 10 km Cycle Time Trial

This study investigated the effects of the inclusion of a postactivation potentiation (PAP) specific warm-up (WU) consisting of all-out sprints on 10 kilometre cycling time trial (10 km-TT) pacing and performance. Following familiarization, thirteen well-trained male participants performed two 10 km cycle laboratory time trials following warm-ups that included either four 8 seconds (s) maximal sprints, or a matched total work performed at a constant exercise intensity. Power output (PO), heart rate (HR), and ratings of perceived exertion (RPE) were measured throughout and blood lactate (BLa) 3 minutes post exercise. There were no significant differences in total performance time, PO in any 2 km segment, RPE, or post-exercise BLa between conditions. Some significant differences (P<0.05) were observed in heart rate and cadence between 2 km segments. Addition of four all-out sprints to the WU did not improve 10 km time trial performance or alter pacing strategy displayed. This suggests that maximal sprinting in a warming up might not be an effective strategy to improve cycling time trial endurance performance

Effects of Reallocating Time Spent in Different Physical Activity Intensities on Sarcopenia Risk in Older Adults: An Isotemporal Substitution Analysis

The role of daily time spent sedentary and in different intensities of physical activity (PA) for the maintenance of muscle health currently remains unclear. Therefore, we investigated the impact of reallocating time spent in different PA intensities on sarcopenia risk in older adults, while considering PA type (muscle strengthening activities, MSA) and protein intake. In a sample of 235 community-dwelling older adults (65–70 years), a sarcopenia risk score (SRS) was created based on muscle mass assessed by bioimpedance, together with handgrip strength and performance on the five times sit-to-stand (5-STS) test assessed by standardized procedures. Time spent in light-intensity PA (LPA), moderate-to-vigorous PA (MVPA), and being sedentary was assessed by accelerometry, and PA type (MSA) by self-report. Linear regression models based on isotemporal substitution were employed. Reallocating sedentary time to at least LPA was significantly (p p < 0.05) lower SRS. Our results emphasize the importance of displacing sedentary behaviours for more active pursuits, where PA of even light intensities may alleviate age-related deteriorations of muscle health in older adults

Bone marrow mesenchymal stromal cells can render multiple myeloma cells resistant to cytotoxic machinery of CAR T cells through inhibition of apoptosis

Purpose: The microenvironment of multiple myeloma (MM) can critically impair therapy outcome, including immunotherapies. In this context, we have earlier demonstrated that bone marrow mesenchymal stromal cells (BMMSC) protect MM cells against the lytic machinery of MM-reactive cytotoxic T cells (CTL) and daratumumab-redirected natural killer (NK) cells through the upregulation of antiapoptotic proteins Survivin and Mcl-1 in MM cells. Here, we investigated the significance of this mode of immune escape on T cells engineered to express chimeric antigen receptors (CAR T cells). Experimental Design: We tested the cytolytic ability of a panel of 10 BCMA-, CD38-, and CD138-specific CAR T cells with different affinities against a model MM cell line and against patient-derived MM cells in the presence versus absence of BMMSCs. Results: Although BMMSCs hardly protected MM cells from lysis by high-affinity, strongly lytic BCMA- and CD38-CAR T cells, they significantly protected against lower affinity, moderately lytic BCMA-, CD38-, and CD138-specific CAR T cells in a cell–cell contact-dependent manner. Overall, there was a remarkable inverse correlation between the protective ability of BMMSCs and the lytic activity of all CAR T cells, which was dependent on CAR affinity and type of costimulation. Furthermore, BMMSC-mediated resistance against CAR T cells was effectively modulated by FL118, an inhibitor of antiapoptotic proteins Survivin, Mcl-1, and XIAP. Conclusions: These results extend our findings on the negative impact of the microenvironment against immunotherapies and suggest that outcome of CAR T cell or conventional CTL therapies could benefit from inhibition of antiapoptotic proteins upregulated in MM cells through BMMSC interactions