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Targeting ageing with rapamycin and its derivatives in humans: a systematic review.
Lee, DJW, Hodzic Kuerec, A, Maier, AB
The lancet. Healthy longevity. 2024;(2):e152-e162
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Rapamycin and its derivatives (rapalogs) are inhibitors of mTOR, a major regulator of the ageing process. We aimed to summarise the effects of rapamycin and its derivatives on the severity of ageing-related physiological changes and disease in adults. A search across five databases yielded 18 400 unique articles, resulting in 19 included studies. Rapamycin and its derivatives improved physiological parameters associated with ageing in the immune, cardiovascular, and integumentary systems of healthy individuals or individuals with ageing-related diseases. Overall, no significant effects on the endocrine, muscular, or neurological systems were found. The effects of rapamycin or its derivatives on the respiratory, digestive, renal, and reproductive systems were not assessed. No serious adverse events attributed to rapamycin and its derivatives were reported in healthy individuals; however, there were increased numbers of infections and increases in total cholesterol, LDL cholesterol, and triglycerides in individuals with ageing-related diseases. Future studies should assess the remaining unexamined systems and test the effects of long-term exposure to rapamycin and its derivatives.
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The Semmelweis Study: a longitudinal occupational cohort study within the framework of the Semmelweis Caring University Model Program for supporting healthy aging.
Ungvari, Z, Tabák, AG, Adany, R, Purebl, G, Kaposvári, C, Fazekas-Pongor, V, Csípő, T, Szarvas, Z, Horváth, K, Mukli, P, et al
GeroScience. 2024;(1):191-218
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The Semmelweis Study is a prospective occupational cohort study that seeks to enroll all employees of Semmelweis University (Budapest, Hungary) aged 25 years and older, with a population of 8866 people, 70.5% of whom are women. The study builds on the successful experiences of the Whitehall II study and aims to investigate the complex relationships between lifestyle, environmental, and occupational risk factors, and the development and progression of chronic age-associated diseases. An important goal of the Semmelweis Study is to identify groups of people who are aging unsuccessfully and therefore have an increased risk of developing age-associated diseases. To achieve this, the study takes a multidisciplinary approach, collecting economic, social, psychological, cognitive, health, and biological data. The Semmelweis Study comprises a baseline data collection with open healthcare data linkage, followed by repeated data collection waves every 5 years. Data are collected through computer-assisted self-completed questionnaires, followed by a physical health examination, physiological measurements, and the assessment of biomarkers. This article provides a comprehensive overview of the Semmelweis Study, including its origin, context, objectives, design, relevance, and expected contributions.
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The effect of glycine administration on the characteristics of physiological systems in human adults: A systematic review.
Soh, J, Raventhiran, S, Lee, JH, Lim, ZX, Goh, J, Kennedy, BK, Maier, AB
GeroScience. 2024;(1):219-239
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Functional decline of physiological systems during ageing leads to age-related diseases. Dietary glycine increases healthy lifespan in model organisms and might decrease inflammation in humans, suggesting its geroprotective potential. This review summarises the evidence of glycine administration on the characteristics of eleven physiological systems in adult humans. Databases were searched using key search terms: 'glycine', 'adult', 'supplementation'/ 'administration'/ 'ingestion'/ 'treatment'. Glycine was administered to healthy and diseased populations (18 and 34 studies) for up to 14 days and 4 months, respectively. The nervous system demonstrated the most positive effects, including improved psychiatric symptoms from longer-term glycine administration in psychiatric populations. While longer-term glycine administration improved sleep in healthy populations, these studies had small sample sizes with a high risk of bias. Larger and long-term studies with more robust study designs in healthy populations to examine the effects of glycine administration on preventing, delaying or reversing the ageing process are warranted.
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Personalization matters: the effect of sex in multivitamin-multimineral-based cancer prevention.
Šelb, J, Cvetko, F, Deutsch, L, Bedrač, L, Kuščer, E, Maier, AB
GeroScience. 2024;(1):1351-1356
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The prevention of non-communicable diseases like cancer contributes to healthy aging. Dietary supplements might support such prevention; their effect likely depends on the personal characteristics of the individuals receiving them. To evaluate the influence of sex on reducing cancer incidence with multivitamin-multimineral (MVM) supplementation, sex-specific results of the efficacy of MVM supplementation for cancer prevention were collected and meta-analyzed (using fixed effect (FE) and random effect (RE) models). Three trials included in the "US Preventive Services Task Force Recommendation Statement Report regarding Vitamin, Mineral, and Multivitamin Supplementation to Prevent Cardiovascular Disease and Cancer" were used, namely, COSMOS, SU.VI.MAX, and PHS2. A total of 28,558 men and 20,542 women were included. Multivitamin-multimineral supplementation significantly reduced cancer incidence in the entire population (HR 0.93 [95% CI, 0.88-0.99], FE and RE); sex-specific meta-analysis showed beneficial effects of supplementation in men (HR 0.91 [95% CI, 0.85-0.97] (FE)/0.88 [95% CI, 0.77-1.01] (RE)); however, there was no effect in women (HR 1.00 [95% CI, 0.88-1.14], FR and RE); (Pdifference = 0.17). Sex could influence the effect of MVM supplementation in reducing cancer incidence, with supplementation being effective only in male individuals. These results might be informative for future research and public health policy makers.
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The role of lifestyle factors in cognitive health and dementia in oldest-old: A systematic review.
Ye, KX, Sun, L, Wang, L, Khoo, ALY, Lim, KX, Lu, G, Yu, L, Li, C, Maier, AB, Feng, L
Neuroscience and biobehavioral reviews. 2023;:105286
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Oldest-old is the fastest growing segment of society. A substantial number of these individuals are cognitively impaired or demented. Given the lack of a cure, attention is directed to lifestyle interventions that could help alleviate the stress in patients, their families, and society. The aim of this review was to identify lifestyle factors with important roles in dementia prevention in oldest-old. Searches were conducted in PubMed, EMBASE, Scopus and Web of Science. We identified 27 observational cohort studies that met the inclusion criteria. Results showed that eating a healthy diet with plenty of fruits and vegetables, and participation in leisure and physical activities may protect against cognitive decline and cognitive impairment among oldest-old regardless of the APOE genotype. Combined lifestyles may generate multiplicative effects than individual factors. This is the first review known to systematically examine the association between lifestyle and cognitive health in oldest-old. Lifestyle interventions for diet, leisure, or a combination of lifestyles could be beneficial for cognitive function in oldest-old. Interventional studies are warranted to strengthen the evidence.
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Nutrition Intervention Informed by Indirect Calorimetry Compared to Predictive Equations to Achieve Weight Goals in Geriatric Rehabilitation Inpatients: The NEED Study.
Hettiarachchi, J, Fetterplace, K, Maier, AB, Reijnierse, EM
The journal of nutrition, health & aging. 2023;(10):833-841
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OBJECTIVES To assess if nutritional interventions informed by indirect calorimetry (IC), compared to predictive equations, show greater improvements in achieving weight goals, muscle mass, strength, physical and functional performance. DESIGN Quasi-experimental study. SETTING AND PARTICIPANTS Geriatric rehabilitation inpatients referred to dietitian. INTERVENTION AND MEASUREMENTS Patients were allocated based on admission ward to either the IC or equation (EQ) group. Measured resting metabolic rate (RMR) by IC was communicated to the treating dietitian for the IC group but concealed for the EQ group. Achieving weight goals was determined by comparing individualised weight goals with weight changes from inclusion to discharge (weight gain/loss: >2% change, maintenance: ≤2%). Muscle mass, strength, physical and functional performance were assessed at admission and discharge. Food intake was assessed twice over three-days at inclusion and before discharge using plate waste observation. RESULTS Fifty-three patients were included (IC n=22; EQ n=31; age: 84.3±8.4 years). The measured RMR was lower than the estimated RMR within both groups [mean difference IC -282 (95%CI -490;-203), EQ -273 (-381;-42) kcal/day)] and comparable between-groups (median IC 1271 [interquartile range 1111;1446] versus EQ 1302 [1135;1397] kcal/day, p=0.800). Energy targets in the IC group were lower than the EQ group [mean difference -317 (95%CI -479;-155) kcal/day]. There were no between-group differences in energy intake, achieving weight goals, changes in muscle mass, strength, physical and functional performance. CONCLUSIONS In geriatric rehabilitation inpatients, nutritional interventions informed by IC compared to predictive equations showed no greater improvement in achieving weight goals, muscle mass, strength, physical and functional performance. IC facilitates more accurate determination of energy targets in this population. However, evidence for the potential benefits of its use in nutrition interventions was limited by a lack of agreement between patients' energy intake and energy targets.
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Consensus guidelines for sarcopenia prevention, diagnosis and management in Australia and New Zealand.
Zanker, J, Sim, M, Anderson, K, Balogun, S, Brennan-Olsen, SL, Dent, E, Duque, G, Girgis, CM, Grossmann, M, Hayes, A, et al
Journal of cachexia, sarcopenia and muscle. 2023;(1):142-156
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BACKGROUND Sarcopenia is an age-associated skeletal muscle condition characterized by low muscle mass, strength, and physical performance. There is no international consensus on a sarcopenia definition and no contemporaneous clinical and research guidelines specific to Australia and New Zealand. The Australian and New Zealand Society for Sarcopenia and Frailty Research (ANZSSFR) Sarcopenia Diagnosis and Management Task Force aimed to develop consensus guidelines for sarcopenia prevention, assessment, management and research, informed by evidence, consumer opinion, and expert consensus, for use by health professionals and researchers in Australia and New Zealand. METHODS A four-phase modified Delphi process involving topic experts and informed by consumers, was undertaken between July 2020 and August 2021. Phase 1 involved a structured meeting of 29 Task Force members and a systematic literature search from which the Phase 2 online survey was developed (Qualtrics). Topic experts responded to 18 statements, using 11-point Likert scales with agreement threshold set a priori at >80%, and five multiple-choice questions. Statements with moderate agreement (70%-80%) were revised and re-introduced in Phase 3, and statements with low agreement (<70%) were rejected. In Phase 3, topic experts responded to six revised statements and three additional questions, incorporating results from a parallel Consumer Expert Delphi study. Phase 4 involved finalization of consensus statements. RESULTS Topic experts from Australia (n = 62, 92.5%) and New Zealand (n = 5, 7.5%) with a mean ± SD age of 45.7 ± 11.8 years participated in Phase 2; 38 (56.7%) were women, 38 (56.7%) were health professionals and 27 (40.3%) were researchers/academics. In Phase 2, 15 of 18 (83.3%) statements on sarcopenia prevention, screening, assessment, management and future research were accepted with strong agreement. The strongest agreement related to encouraging a healthy lifestyle (100%) and offering tailored resistance training to people with sarcopenia (92.5%). Forty-seven experts participated in Phase 3; 5/6 (83.3%) revised statements on prevention, assessment and management were accepted with strong agreement. A majority of experts (87.9%) preferred the revised European Working Group for Sarcopenia in Older Persons (EWGSOP2) definition. Seventeen statements with strong agreement (>80%) were confirmed by the Task Force in Phase 4. CONCLUSIONS The ANZSSFR Task Force present 17 sarcopenia management and research recommendations for use by health professionals and researchers which includes the recommendation to adopt the EWGSOP2 sarcopenia definition in Australia and New Zealand. This rigorous Delphi process that combined evidence, consumer expert opinion and topic expert consensus can inform similar initiatives in countries/regions lacking consensus on sarcopenia.
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Associations of objectively measured physical activity and sedentary behaviour with fall-related outcomes in older adults: A systematic review.
Ramsey, KA, Zhou, W, Rojer, AGM, Reijnierse, EM, Maier, AB
Annals of physical and rehabilitation medicine. 2022;(2):101571
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BACKGROUND Higher physical activity (PA) and lower sedentary behaviour (SB) are associated with better muscle strength, balance, and functional ability, which are imperative for avoiding falls. This systematic review aimed to describe the association between objectively measured PA and SB with falls, fear of falling, and fractures. METHODS Six databases were searched from inception to July 21, 2020 for articles reporting the association of objectively measured PA/SB with falls, fear of falling, and/or fractures in community-dwelling older adults ≥60 years old. Results were synthesized in effect-direction heat maps and albatross plots expressed as Pearson's correlation coefficients (R). RESULTS A total of 43 articles were included, representing 27,629 (range 26-5545) community-dwelling older adults (mean [SD] age 76.6 [8.4] years, 47% female). Longitudinal associations were reported in 13 articles and cross-sectional associations in 30. Falls were reported in 11 articles, fear of falling in 18 and fractures in 2. Higher PA and lower SB were associated with less fear of falling (median [interquartile range] Rs = steps: -0.214 [0.249; -0.148], total PA: -0.240 [0.267; -0.144], and moderate-to-vigorous PA: -0.180 [0.382; -0.121]), but these associations did not extend to falls or fractures, which showed inconsistent effect directions. CONCLUSION Fear of falling is associated with less engagement in PA and more SB, thus indicating that it is a psychological barrier to an active lifestyle. Varying effect directions for associations between PA and SB with falls and fractures may provide evidence for non-linear associations and require further research considering details of the fall or fracture incident. PROSPERO REGISTRATION NUMBER CRD42018103910.
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Handgrip strength rather than chair stand test should be used to diagnose sarcopenia in geriatric rehabilitation inpatients: REStORing health of acutely unwell adulTs (RESORT).
Verstraeten, LMG, de Haan, NJ, Verbeet, E, van Wijngaarden, JP, Meskers, CGM, Maier, AB
Age and ageing. 2022;(11)
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BACKGROUND according to the revised sarcopenia definition proposed by the European Working Group on Sarcopenia in Older People (EWGSOP2) and revised definition of the Asian Working Group for Sarcopenia (AWGS2019), handgrip strength (HGS) and chair stand test (CST) can be used interchangeably as initial diagnostic measures. OBJECTIVE to assess the agreement between sarcopenia prevalence, using either HGS or CST, and their association with adverse outcomes in geriatric rehabilitation inpatients. METHODS REStORing health of acutely unwell adulTs is an observational, longitudinal cohort of geriatric rehabilitation inpatients. Cohen's kappa (κ) was used to assess the agreement between sarcopenia prevalence (no, probable and confirmed and severe sarcopenia) according to EWGSOP2 and AWGS2019 using either HGS or CST. Associations between HGS and CST and readmission, institutionalisation and mortality were assessed by binomial regression. RESULTS patients (n = 1,250, 57% females) had a median age of 83.1 years (interquartile range: [77.5-88.3]). There was no agreement between probable sarcopenia prevalence using HGS or CST for EWGSOP2 and AWGS2019, respectively (HGS: 70.9% and 76.2%; CST: 95.5% and 98.4%; κ = 0.08 and 0.02). Agreement between confirmed and severe sarcopenia prevalence using either HGS or CST was strong to almost perfect. HGS was associated with 3-month institutionalisation and 3-month and 1-year mortality, whereas CST was not associated. CONCLUSIONS HGS and CST cannot be used interchangeably as diagnostic measures for probable sarcopenia in geriatric rehabilitation inpatients. CST is not useful to predict adverse outcomes in geriatric rehabilitation inpatients.
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The Physical Activity and Nutritional INfluences in Ageing (PANINI) Toolkit: A Standardized Approach towards Physical Activity and Nutritional Assessment of Older Adults.
Ramsey, KA, Meskers, CGM, Trappenburg, MC, Bacalini, MG, Delledonne, M, Garagnani, P, Greig, C, Kallen, V, van Meeteren, N, van Riel, N, et al
Healthcare (Basel, Switzerland). 2022;(6)
Abstract
Assessing multiple domains of health in older adults requires multidimensional and large datasets. Consensus on definitions, measurement protocols and outcome measures is a prerequisite. The Physical Activity and Nutritional INfluences In Ageing (PANINI) Toolkit aims to provide a standardized toolkit of best-practice measures for assessing health domains of older adults with an emphasis on nutrition and physical activity. The toolkit was drafted by consensus of multidisciplinary and pan-European experts on ageing to standardize research initiatives in diverse populations within the PANINI consortium. Domains within the PANINI Toolkit include socio-demographics, general health, nutrition, physical activity and physical performance and psychological and cognitive health. Implementation across various countries, settings and ageing populations has proven the feasibility of its use in research. This multidimensional and standardized approach supports interoperability and re-use of data, which is needed to optimize the coordination of research efforts, increase generalizability of findings and ultimately address the challenges of ageing.