Search

The inaugural Canadian Conferences on Translational Geroscience were held as 2 complementary sessions in October and November 2023. The conferences explored the profound interplay between the biology of aging, social determinants of health, the potential societal impact of geroscience, and the maintenance of health in aging individuals. Although topics such as cellular senescence, molecular and genetic determinants of aging, and prevention of chronic disease were addressed, the conferences went on to emphasize practical applications for enhancing older people's quality of life. This article summarizes the proceeding and underscores the synergy between clinical and fundamental studies. Future directions highlight national and global collaborations and the crucial integration of early-career investigators. This work charts a course for a national framework for continued innovation and advancement in translational geroscience in Canada., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Weightlessness during spaceflight can harm various bodily systems, including bone density, muscle mass, strength and cognitive functions. Exercise appears to somewhat counteract these effects. A terrestrial model for this is head-down bedrest (HDBR), simulating gravity loss. This mirrors challenges faced by older adults in extended bedrest and space environments. The first Canadian study, backed by the Canadian Space Agency, Canadian Institutes of Health Research, and Canadian Frailty Network, aims to explore these issues. The study seeks to: (1) scrutinize the impact of 14-day HDBR on physiological, psychological and neurocognitive systems, and (2) assess the benefits of exercise during HDBR. Eight teams developed distinct protocols, harmonized in three videoconferences, at the McGill University Health Center. Over 26 days, 23 participants aged 55-65 underwent baseline measurements, 14 days of -6° HDBR, and 7 days of recovery. Half did prescribed exercise thrice daily combining resistance and endurance exercise for a total duration of 1 h. Assessments included demographics, cardiorespiratory fitness, bone health, body composition, quality of life, mental health, cognition, muscle health and biomarkers. This study has yielded some published outcomes, with more forthcoming. Findings will enrich our comprehension of HDBR effects, guiding future strategies for astronaut well-being and aiding bedrest-bound older adults. By outlining evidence-based interventions, this research supports both space travellers and those enduring prolonged bedrest., (© 2024 The Authors. Experimental Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

Introduction: Head-down bed rest (HDBR) has long been used as an analog to microgravity, and it also enables studying the changes occurring with aging. Exercise is the most effective countermeasure for the deleterious effects of inactivity. The aim of this study was to investigate the efficacy of an exercise countermeasure in healthy older participants on attenuating musculoskeletal deconditioning, cardiovascular fitness level, and muscle strength during 14 days of HDBR as part of the standard measures of the Canadian Space Agency., Methods: Twenty-three participants (12 males and 11 females), aged 55-65 years, were admitted for a 26-day inpatient stay at the McGill University Health Centre. After 5 days of baseline assessment tests, they underwent 14 days of continuous HDBR followed by 7 days of recovery with repeated tests. Participants were randomized to passive physiotherapy or an exercise countermeasure during the HDBR period consisting of 3 sessions per day of either high-intensity interval training (HIIT) or low-intensity cycling or strength exercises for the lower and upper body. Peak aerobic power (V̇O2peak) was determined using indirect calorimetry. Body composition was assessed by dual-energy X-ray absorptiometry, and several muscle group strengths were evaluated using an adjustable chair dynamometer. A vertical jump was used to assess whole-body power output, and a tilt test was used to measure cardiovascular and orthostatic challenges. Additionally, changes in various blood parameters were measured as well as the effects of exercise countermeasure on these measurements., Results: There were no differences at baseline in main characteristics between the control and exercise groups. The exercise group maintained V̇O2peak levels similar to baseline, whereas it decreased in the control group following 14 days of HDBR. Body weight significantly decreased in both groups. Total and leg lean masses decreased in both groups. However, total body fat mass decreased only in the exercise group. Isometric and isokinetic knee extension muscle strength were significantly reduced in both groups. Peak velocity, flight height, and flight time were significantly reduced in both groups with HDBR., Conclusion: In this first Canadian HDBR study in older adults, an exercise countermeasure helped maintain aerobic fitness and lean body mass without affecting the reduction of knee extension strength. However, it was ineffective in protecting against orthostatic intolerance. These results support HIIT as a promising approach to preserve astronaut health and functioning during space missions, and to prevent deconditioning as a result of hospitalization in older adults., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Objective: To estimate the extent to which comorbidity and lifestyle factors were associated with physical frailty in middle-aged and older Canadians living with HIV., Design: Cross-sectional analysis of 856 participants from the Canadian Positive Brain Health Now cohort., Methods: The frailty indicator phenotype was adapted from Fried's criteria using self-report items. Univariate logistic regression and classification and regression tree (CaRT) models were used to identify the most relevant independent contributors to frailty., Results: In all, 100 men (14.0%) and 26 women (19.7%) were identified as frail (≥ 3/5 criteria) for an overall prevalence of 15.2%. Nine comorbidities showed an influential association with frailty. The most influential comorbidities were hypothyroidism [odds ratio (OR) = 2.55, 95% confidence interval (CI): 1.29-5.03] and arthritis (OR = 2.54, 95% CI: 1.58-4.09). Additionally, tobacco (OR = 1.79, 95% CI: 1.05-3.04) showed an association. Any level of alcohol consumption showed a protective effect for frailty. The CaRT model showed nine pathways that led to frailty. Arthritis was the most discriminatory variable followed by alcohol, hypothyroidism, tobacco, cancer, cannabis, liver disease, kidney disease, osteoporosis, lung disease and peripheral vascular disease. The prevalence of physical frailty for people with arthritis was 27.4%; with additional cancer or tobacco and alcohol the prevalence rates were 47.1% and 46.1%, respectively. The protective effect of alcohol consumption evident in the univariate model appeared again in the CaRT model, but this effect varied. Cognitive frailty (19.5% overall) and emotional frailty (37.9% overall) were higher than the prevalence of physical frailty., Conclusions: Specific comorbidities and tobacco use were implicated in frailty, suggesting that it is comorbidities causing frailty. However, some frailty still appears to be HIV-related. The higher prevalence of cognitive and emotional frailty highlights the fact that physical frailty should not be the only focus in HIV., (© 2022 British HIV Association.)

Importance: Cross-sectional studies have shown that combined low muscle mass and strength are associated with cognitive impairment. Whether low muscle mass, reflective of physiologic reserve, is independently associated with faster cognitive decline remains unknown., Objective: To investigate the associations between low muscle mass and cognitive decline in 3 distinct domains among adults aged at least 65 years., Design, Setting, and Participants: The Canadian Longitudinal Study on Aging is a prospective population-based cohort study of community-dwelling adults. Enrollment occurred from 2011 to 2015 with a 3-year follow-up. Analyses for this study were conducted on those aged at least 65 years from April 24 to August 12, 2020., Exposure: Appendicular lean soft tissue mass (ALM) was assessed by dual energy x-ray absorptiometry. Low ALM was identified using the sex-specific Canadian cut points., Main Outcomes and Measures: Memory was assessed using the Rey auditory verbal learning test. Executive function was assessed using the mental alternation test, Stroop high interference (words/dot) test, the animal fluency test, and the controlled oral word association test. Psychomotor speed was assessed using computer-administered choice reaction time. Composite scores by domain were created., Results: Of 8279 participants, 4003 (48%) were female, 8005 (97%) were White, and the mean (SD) age was 72.9 (5.6) years. A total of 1605 participants (19.4%) had low ALM at baseline. Participants with low ALM were older, had lower body mass index and physical activity level. The presence of low ALM at baseline was associated with faster 3-year cognitive decline in executive functions and psychomotor speed from multiple linear regressions. After adjusting for covariates including age, level of education, percentage body fat, and handgrip strength, low ALM remained independently associated with executive function decline (standardized β: -0.032; P = .03) only. Low ALM was not associated with memory., Conclusions and Relevance: This cohort study found longitudinal associations between low ALM and cognition in aging. Identification of older adults with low muscle mass, a targetable modifiable factor, may help estimate those at risk for accelerated executive function decline. Further longer-term investigation of associations is warranted.

Background: Master athletes (MAs) prove that preserving a high level of physical function up to very late in life is possible, but the mechanisms responsible for their high function remain unclear., Methods: We performed muscle biopsies in 15 octogenarian world-class track and field MAs and 14 non-athlete age/sex-matched controls (NA) to provide insights into mechanisms for preserving function in advanced age. Muscle samples were assessed for respiratory compromised fibers, mitochondrial DNA (mtDNA) copy number, and proteomics by liquid-chromatography mass spectrometry., Results: MA exhibited markedly better performance on clinical function tests and greater cross-sectional area of the vastus lateralis muscle. Proteomics analysis revealed marked differences, where most of the ~800 differentially represented proteins in MA versus NA pertained to mitochondria structure/function such as electron transport capacity (ETC), cristae formation, mitochondrial biogenesis, and mtDNA-encoded proteins. In contrast, proteins from the spliceosome complex and nuclear pore were downregulated in MA. Consistent with proteomics data, MA had fewer respiratory compromised fibers, higher mtDNA copy number, and an increased protein ratio of the cristae-bound ETC subunits relative to the outer mitochondrial membrane protein voltage-dependent anion channel. There was a substantial overlap of proteins overrepresented in MA versus NA with proteins that decline with aging and that are higher in physically active than sedentary individuals. However, we also found 176 proteins related to mitochondria that are uniquely differentially expressed in MA., Conclusions: We conclude that high function in advanced age is associated with preserving mitochondrial structure/function proteins, with underrepresentation of proteins involved in the spliceosome and nuclear pore complex. Whereas many of these differences in MA appear related to their physical activity habits, others may reflect unique biological (e.g., gene, environment) mechanisms that preserve muscle integrity and function with aging., Funding: Funding for this study was provided by operating grants from the Canadian Institutes of Health Research (MOP 84408 to TT and MOP 125986 to RTH). This work was supported in part by the Intramural Research Program of the National Institute on Aging, NIH, Baltimore, MD, USA., Competing Interests: CU, SS, AL, RM, NM, MF, JM, TT, LF, RH No competing interests declared

Background: The co-occurrence of slow walking speed and subjective cognitive complaint (SCC) in non-demented individuals defines motoric cognitive risk syndrome (MCR), which is a pre-dementia stage. There is no information on the association between MCR and incident dementia in Québec's older population., Objective: The study aims to examine the association of MCR and its individual components (i.e. SCC and slow walking speed) with incident dementia in community-dwelling older adults living in the province of Québec (Canada)., Design: Québec older people population-based observational cohort study with 3 years of follow-up., Setting: Community dwellings., Subjects: A subset of participants (n = 1,098) in 'Nutrition as a determinant of successful aging: The Québec longitudinal study' (NuAge)., Methods: At baseline, participants with MCR were identified. Incident dementia was measured at annual follow-up visits using the Modified Mini-Mental State (≤79/100) test and Instrumental Activity Daily Living scale (≤6/8) score values., Results: The prevalence of MCR was 4.2% at baseline and the overall incidence of dementia was 3.6%. MCR (Hazard Ratio (HR) = 5.18, with 95% confidence interval (CI) = [2.43-11.03] and P ≤ 0.001) and SCC alone (HR = 2.54, with 95% CI = [1.33-4.85] and P = 0.005) were associated with incident dementia, but slow walking speed was not (HR = 0.81, with 95%CI = [0.25-2.63] and P = 0.736)., Conclusions: MCR and SCC are associated with incident dementia in NuAge study participants., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Fried's Phenotype Model of Frailty (PMF) postulates that frailty is a syndrome. Features of a syndrome are a heterogeneous population that can be split into at least two classes, those presenting and those not presenting the syndrome. Syndromes are characterized by a specific mixture of signs and symptoms which increase in prevalence, from less to more severe classes. So far, the null hypothesis of homogeneity - signs and symptoms of frailty cannot identify at least two classes - has been tested using Latent Class Analysis (LCA) on the five dichotomized components of PMF (unintentional weight loss, exhaustion, weakness, slowness, and low physical activity). The aim of this study is to investigate further the construct validity of frailty as a syndrome using the extension offered by Factor Mixture Models (FMM)., Methods: LCA on dichotomized scores and FMM on continuous scores were conducted to test homogeneity on the five PMF components in a sample of 1643 community-dwelling older adults living in Québec, Canada (FRéLE)., Results: With dichotomized LCA, three frailty classes were found: robust, prefrail and frail, and the hypothesis of homogeneity was rejected. However, in FMM, frailty was better represented as a continuous variable than as latent heterogeneous classes. Thus, the PMF measurement model of frailty did not meet the features of a syndrome in this study., Conclusion: Using the FRéLE cohort, the PMF measurement model validity is questioned. Valid measurement of a syndrome depends on an understanding of its etiological factors and pathophysiological processes, and on a modelling of how the measured components are linked to these processes. Without these features, assessing frailty in a clinical setting may not improve patient health. Research on frailty should address these issues before promoting its use in clinical settings.

Background: Aging is associated with sarcopenia (low muscle mass) and dynapenia (low muscle strength) leading to disability and mortality. Widely used previous cut-points for sarcopenia were established from dated, small, or pooled cohorts. We aimed to identify cut-points of low strength as a determinant of impaired physical performance and cut-points of low appendicular lean mass (ALM) as a predictor of low strength in a single, large, and contemporary cohort of community-dwelling older adults and compare these criteria with others., Methods: Cross-sectional analyses were conducted on baseline data from 4725 and 4363 community-dwelling men and women (65-86 years, 96.8% Caucasian) of the Canadian longitudinal study on aging comprehensive cohort. Physical performance was evaluated from gait speed, timed up-and-go, chair rise, and balance tests; a weighted-sum score was computed using factor analysis. Strength was measured by handgrip dynamometry; ALM, by dual-energy X-ray absorptiometry and ALM index (ALMI; kg/m 2 ), was calculated. Classification and regression tree analyses determined optimal sex-specific cut-points of ALMI predicting low strength and of strength predicting impaired physical performance (score < 1.5 SD below the sex-specific mean)., Results: Modest associations were found between ALMI and strength and between strength and physical performance score in both sexes. ALMI was not an independent predictor of physical performance score. Cut-points of <33.1 and <20.4 kg were found to define dynapenia in men and in women, respectively, corresponding to 21.5% and 24.0% prevalence rates. Sarcopenia cut-points were <7.76 kg/m 2 in men and <5.72 kg/m 2 in women; prevalence rates of 21.7% and 13.7%. Overall, 8.3% of men and 5.5% of women had sarco-dynapenia. Sarcopenic were older and had lower fat mass and body mass index (BMI) than non-sarcopenic participants. While the agreement between current criteria and the updated European Working Group for Sarcopenia in Older Persons recommendations was fair, we found only slight agreement with the Foundation for the National Institute of Health sarcopenia project. Older persons identified with sarcopenia as per the Foundation for the National Institute of Health criteria (using ALM/BMI as the index) have higher BMI and fat mass compared with non-sarcopenic and have normal ALMI as per our criteria., Conclusions: The proposed function-derived cut-points established from this single, large, and contemporary Canadian cohort should be used for the identification of sarcopenia and dynapenia in Caucasian older adults. We advise on using criteria based on ALMI in the diagnosis of sarcopenia. The modest agreement between sarcopenia and dynapenia denotes potential distinct health implications justifying to study both components separately., (© 2019 The Authors Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.)

Background: A new paradigm is emerging in which mobility and cognitive impairments, previously studied, diagnosed, and managed separately in older adults, are in fact regulated by shared brain resources. Deterioration in these shared brain mechanisms by normal aging and neurodegeneration increases the risk of developing dementia, falls, and fractures. This new paradigm requires an integrated approach to measuring both domains. We aim to identify a complementary battery of existing tests of mobility and cognition in community-dwelling older adults that enable assessment of motor-cognitive interactions., Methods: Experts on mobility and cognition in aging participated in a semistructured consensus based on the Delphi process. After performing a scoping review to select candidate tests, multiple rounds of consultations provided structured feedback on tests that captured shared characteristics of mobility and cognition. These tests needed to be sensitive to changes in both mobility and cognition, applicable across research studies and clinics, sensitive to interventions, feasible to perform in older adults, been previously validated, and have minimal ceiling/floor effects., Results: From 17 tests appraised, 10 tests fulfilled prespecified criteria and were selected as part of the "Core-battery" of tests. The expert panel also recommended a "Minimum-battery" of tests that included gait speed, dual-task gait speed, the Montreal Cognitive Assessment and Trail Making Test A&B., Conclusions: A standardized assessment battery that captures shared characteristics of mobility and cognition seen in aging and neurodegeneration may increase comparability across research studies, detection of subtle or common reversible factors, and accelerate research progress in dementia, falls, and aging-related disabilities., (© The Author(s) 2018. Published by Oxford University Press on behalf of The Gerontological Society of America.)

Frailty is a still-evolving concept of a complex phenomenon. There are several algorithms and strategies for assessing frailty syndrome, but currently, no universally accepted definition or measurement protocol has been determined. Consequently, the biological cause(s) of frailty are also poorly defined. Much circumstantial experimental data point to the dysregulation of several key physiological systems, including the neuroendocrine, musculoskeletal, metabolic and immune/inflammatory systems, resulting from alterations in functional reserves. Immune dysregulation and inflammation as causes of frailty have gained some support from the results of longitudinal studies, but a true causal relationship has not been established. This chapter will describe the immune/inflammatory alterations found in frailty and their putative causal relationships with this state., (2015 S. Karger AG, Basel.)

This study examines the association between sodium intake and its interaction with physical activity on cognitive function over 3 years in older adults residing in Québec, Canada. We analyzed a subgroup from the NuAge cohort (aged 67-84 years) with nutrient intake data, including sodium, from a food frequency questionnaire administered at baseline. Baseline physical activity was assessed using the Physical Activity Scale for the Elderly (PASE; high-low). Modified Mini Mental State Examination (3MS) was administered at baseline and annually for 3 additional years. Controlling for age, sex, education, waist circumference, diabetes, and dietary intakes, analyses showed an association between sodium intake and cognitive change over time in the low PASE group only. Specifically, in the low PASE group, elders in the low sodium intake tertile displayed better cognitive performance over time (mean decline in 3MS over years: mean [M] = -0.57, standard error [SE] = 0.002) compared with the highest (M = -1.72, SE = 0.01) and mid sodium intake (M = -2.07, SE = 0.01) groups. This finding may have significant public health implications, emphasizing the importance of addressing multiple lifestyle factors rather than a single domain effect on brain health., (Copyright © 2012 Elsevier Inc. All rights reserved.)