Effects of aging on resting metabolic rate: A systematic review and - Brazilian Journals
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Brazilian Journal of Health Review 17867 ISSN: 2595-6825 Effects of aging on resting metabolic rate: A systematic review and meta-analysis Efeito do envelhecimento na taxa metabólica de repouso: uma revisão sistemática e meta-análise DOI:10.34119/bjhrv4n4-266 Recebimento dos originais: 20/07/2021 Aceitação para publicação: 20/08/2021 Paulo Roberto Hernandes Júnior Graduando em Medicina pela Universidade de Vassouras Instituição: Universidade de Vassouras Endereço: Av. Expedicionário Oswaldo de Almeida Ramos, 278, Centro, Vassouras, RJ, Brasil, CEP: 27700-000 E-mail: paulorh.eng@gmail.com Bruno Carvalho Brandão Graduando em Medicina pela Universidade de Brasília Instituição: Universidade de Brasília Endereço: Campus Darcy Ribeiro, s/n, Asa Norte, Brasília, DF, Brasil, CEP: 70910-900 E-mail: bruno109medunb@gmail.com Patrick de Abreu Cunha Lopes Instituição: Universidade de Vassouras Endereço: Av. Expedicionário Oswaldo de Almeida Ramos, 278, Centro, Vassouras, RJ, Brasil, CEP: 27700-000 E-mail: patrick.abreu33@gmail.com Amanda Veiga Sardeli Doutora, pela Universidade Estadual de Campinas Instituição: University of Birmingham Endereço: Mindelsohn Way, Queen Elizabeth Hospital Research Labs, Birmingham, Reino Unido, CEP: B15 2WB E-mail: amandavsardeli@gmail.com Paula Pitta de Resende Côrtes Mestre, pela Universidade Federal Fluminense Instituição: Universidade de Vassouras Endereço: Av. Expedicionário Oswaldo de Almeida Ramos, 278, Centro, Vassouras, RJ, Brasil, CEP: 27700-000 E-mail: paulapitta@yahoo.com.br Brazilian Journal of Health Review, Curitiba, v.4, n.4, p.17867-17882 jul./aug. 2021
Brazilian Journal of Health Review 17868 ISSN: 2595-6825 ABSTRACT Objective. To meta-analyze previous literature in order to find a consensus regarding aging effects on resting metabolic rate (RMR) and to identify the main players in this process. Methods. Through a search on PubMed eighteen trials comparing RMR between older and young adults were included for meta-analysis. Results. Older adults had significantly lower RMR than young adults (-437 kJ/d [-591; 283], p
Brazilian Journal of Health Review 17869 ISSN: 2595-6825 determining component of living. The theoretical expectation that individuals who are most efficient at utilizing energy should survive the longest has been shown by the negative association between RMR and longevity 2–4. In fact, when RMR is adjusted for age, sex, and body composition, lower RMR predicts health and longevity, suggesting that higher RMR is a risk factor for mortality in humans 3,5. On the other hand, in human cohort studies show that aging per se reduces RMR, which is contradictory to previous information, given that aging is the main independent risk factor for mortality 6. Furthermore, not all studies agree that older adults have lower RMR than young individuals. The variation in those differences may be related not just by the known differences in RMR between men and women, but also due to differences in body composition among older and young adults among the studies. It is noteworthy that transient increases in metabolic rate promoted by physical 7,8 activity, for example, are expected to be beneficial . However, the persistently higher basal metabolic rate may be harmful, accelerating the disease progression and anticipating mortality 3,9. Many confounding factors such as sex and body fat may lead to these inconclusive results. Thus, the aim of this study is to meta-analyze previous literature in order to find a consensus regarding aging effects on RMR, restricting the comparison to health subjects at baseline condition. The results of this meta-analysis will support a wide range of research focusing on metabolism, health, and longevity. 2 METHODS This review was reported according to PRISMA (Preferred Reporting Items for systematic Reviews and Meta-Analyses) Guidelines 10. SEARCH STRATEGY The search on PubMed was performed in February 2020. The search combined the synonyms of aging and metabolism, in which the controlled descriptors were searched accordingly (MeSh) and the non-controlled descriptors were searched in the titles and abstracts of the studies. The search targeted cross-sectional studies comparing resting metabolic rate assessed by indirect calorimetry between young and older adults. There was no restriction for date of publication, nonetheless only studies written in English language were selected. Brazilian Journal of Health Review, Curitiba, v.4, n.4, p.17867-17882 jul./aug. 2021
Brazilian Journal of Health Review 17870 ISSN: 2595-6825 STUDY SELECTION Two reviewers worked on the selection of studies, considering the following inclusion criteria: (Population) healthy adults; (Intervention/effect) age difference between groups; (Comparator) younger group; (Outcome) Resting metabolic rate; (Study type) Observational studies. The exclusion criteria were not original studies, not assessing resting metabolic rate, comparing children or teenagers, not English Language, animal study, acute effects, not testing ageing effects, and no access to full texts. Resting 11,12 metabolic rate assessed by equation estimates were not accepted to minimize bias since these equations are not as reliable as indirect calorimetry 13,14. Details of this process are described in Figure 1. DATA COLLECTION The data collection was performed by two independent reviewers. Means and a measure of dispersion (standard deviation, standard error or 95%CI) of age and resting metabolic rate were extracted for each age group. Mean, standard deviation (SD) and sample number (n) were used for RMR analysis. Standard error (SE) was converted to SD by the equation SD = SE × (√n) , if SD had not been provided in the original study. The 95% confidence intervals were converted to SD considering the equation (√n ∗ (UL − LL)/[2 ∗ T. INV (0.05; n − 1)] , where n is the sample size, UL is the upper limit, LL is the lower limit and T. INV is the function that calculates the left-tailed inverse of the Student’s T distribution 15. Most studies presented their results in kilojoule per day (kJ/d) and thus the main results were presented in this unit measurement. When studies presented data in kilocalorie per minute (kcal/min), it was converted to kJ/d by considering 1 kcal is equal to 4.184 kilojoules, thus the equation was kJ/d = kcal/min * 6024.96 16. For subgroup analysis, first, the difference between groups within each study for mean age and body mass were calculated. These mean differences were clustered in subgroups of “40yrs” according to proximity of the mean differences. Brazilian Journal of Health Review, Curitiba, v.4, n.4, p.17867-17882 jul./aug. 2021
Brazilian Journal of Health Review 17871 ISSN: 2595-6825 STATISTICAL ANALYSIS The outcome measurement was the raw mean difference in resting metabolic rate (kJ/day) between older and young adults, with its respective 95% of confidence interval. One main meta-analysis was performed using Comprehensive Meta-Analysis software, version 3.3.070. When there was statistical significance for heterogeneity, randomized effect models were selected and when there was no statistical significance for heterogeneity, fixed effect models were selected. The inconsistency between studies was presented as a percentage (I2), based on difference between expected heterogeneity (df) and true heterogeneity (Q-value). Egger's tests were performed to check the risk of publication bias in each meta-analysis 17. Subgroup analyses were performed to compare sex (men and women), body mass difference between groups (40yrs). Q tests were applied to group comparisons, considering 95% confidence. Regression analyses were performed using one single model for each continuous body composition variables: body mass, body mass index (BMI), fat mass and fat free mass. QUALITY OF THE EVIDENCE The quality of evidence was assessed by GRADE approach, considering the evaluation items for observational studies for each of the 3 meta-analyses 18. For meta- analysis of observational studies, we begin with 2 points and add one or two points according to effect size, dose-response gradient, and positive influence of confounding factors. It will lead to a quality of evidence that ranges from very low (≤1) to high (4). 3 RESULTS From 198 records initially identified, 5 studies leading to 18 subgroups comparing the baseline metabolism in KJ/min or KJ/day between young and older adults were included in the meta-analysis. Details of the selection of studies can be seen on Figure 1. Brazilian Journal of Health Review, Curitiba, v.4, n.4, p.17867-17882 jul./aug. 2021
Brazilian Journal of Health Review 17872 ISSN: 2595-6825 Figure 1. Flow diagram of studies selection. Legend: RMR: resting metabolic rate. The studies included very different sample sizes in each group; with age differences varying from right next year to 40 years difference; men, women and mixed samples (Table 1). Table 2 shows the exact body mass difference between older and younger ones in each study subgroup, that varied from around 2kg to near 10kg and were clustered for analysis. The differences in other body composition components between older and young adults were not clustered in categorical variables, but since they were tested in regression analysis, their continuous differences used for analysis are detailed on table 2. All studies assessed RMR by indirect calorimetry, using open-circuit which is a 13,14 widely accepted method of measuring RMR . The assessments lasted from 25 to 45 min, in thermoneutral environments and, despite many studies did not describe their orientation for participants fasting and refraining from physical activity, it is expected that they recommended it as part of the RMR protocols. Usually, the first minutes of data are discarded, and the remaining ones must be averaged to the final value of resting 19 metabolic rate. Weir formula was used to determine the energy equivalent of oxygen volume in all studies. Brazilian Journal of Health Review, Curitiba, v.4, n.4, p.17867-17882 jul./aug. 2021
Brazilian Journal of Health Review 17873 ISSN: 2595-6825 Table 1. General characteristics of the studies included. Legend: B: Both sexes; M: Men; NR: not reported; W: women; diff: mean difference category between groups. First author, year Subgroups Older Younger Age (y) Sex Mean SD RMR n Mean SD RMR n Older Younger diff RMR (KJ/d) RMR (KJ/d) (KJ/d) (KJ/d) Krems, 2005 Men 6720 686 84 7867 936 67 68.9 (5.1) 26.8 (3.4) >40 M Krems, 2005 Women 5455 685 132 5809 680 159 69.9 (5.5) 24.8 (3.0) >40 W Luhrmann, 2010 Men 6517 677 55 6809 704 55 76.3 (5.2) 66.3 (5.2) Right M next Luhrmann, 2010 Women 5476 697 107 5566 599 107 76.3 (5.2) 66.3 (5.2) Right W next Krems, 2004 Men 6353 725 107 7371 945 67 66.9 (5.1) 26.8 (3.4) >40 M Krems, 2004 Women 5118 609 178 5374 560 154 67.8 (5.7) 24.8 (3.0) >40 W Lührmann, 2002 Men (65-69yrs) 6762 881 38 6978 746 40 65-69 75
Brazilian Journal of Health Review 17874 ISSN: 2595-6825 Table 2. Body composition of the studies included. Legend: NR: not reported; diff: mean difference between groups. First author, year Subgroups Body mass (kg) BMI (kg/m2) fat mass (kg) Fat free mass (kg) Older Younger diff Older Younger diff Older Younger diff Older Younger diff Krems, 2005 Men 77.7 77 (9.6)
Brazilian Journal of Health Review 17875 ISSN: 2595-6825 Alfonzo-González, Both (40-49.9yrs) 79.0 71.2 (19.6)
Brazilian Journal of Health Review 17876 ISSN: 2595-6825 The 18 groups of comparison led to significant reduction of RMR in older adults compared to younger ones (Figure 2). It was significantly heterogeneous (p
Brazilian Journal of Health Review 17877 ISSN: 2595-6825 Table 3. Subgroup analysis. Legend: k= number of study groups; RMD=raw mean difference (KJ/day); p- value = p-value for significance (P
Brazilian Journal of Health Review 17878 ISSN: 2595-6825 the statistically significant and progressively higher magnitude of RMR reduction with higher age differences between groups. Despite changes in body mass account for some RMR reduction, the main reason 20 for this reduction might be the muscle mass loss . In fact, there is a strong correlation between RMR and muscle mass, which is the main variable used to indirectly predict RMR 20. The influence of muscle mass on RMR was also confirmed by our regression analysis. While body mass, BMI, fat mass and even the age difference per se did not explain the RMR difference between older and younger ones, muscle mass difference significantly predicted it. Additionally, despite both men and women undergo muscle loss along aging, men have greater relative and absolute muscle mass than women, and thus it makes sense that men undergo a more prominent reduction (slope 0.18; women slope: 0.08) across lifespan 20,21. Muscle loss becomes more evident after the 40th decade, mediated by mechanics involving: (1) reduced number of satellite cells and its capability to proliferate; (2) loss of balance between protein synthesis and degradation and responsiveness of anabolic stimulus from nutrients; (3) infiltration of fat and connective tissue, reducing quality of muscle and increasing stiffness; (4) changes in motor units axions and fiber type; (5) increased production of reactive oxygen species and blunted antioxidant system; (6) and inflammation in aging muscle, via production of cytokines which also increases ROS 22. In this way, even among individuals who maintain exercise across the whole life span, reduction in muscle mass is inevitable. The maintenance of physical activity along the life span could be another factor mediating age-induced reduction. The lower level of physical activity among older adults is well known 23, Given the importance of muscle mass within this scenario, American college of sports medicine have highlighted that not just the general physical activity maintenance is important for older adults, but resistance training would be fundamental 24 to regulate RMR . They state that, although the energy expenditure associated with resistance training is not large, increased muscle mass through resistance training is 24 determinant to increase RMR . The benefits of physical activity on RMR are incompletely understood, nevertheless, exercise may prevent or at least attenuate important age alterations such as increased oxidative stress, shifting of energetic needs for other homeostatic mechanisms, rising catabolic state associated with weight loss, and chronic fatigue 5. Brazilian Journal of Health Review, Curitiba, v.4, n.4, p.17867-17882 jul./aug. 2021
Brazilian Journal of Health Review 17879 ISSN: 2595-6825 Despite higher body mass might suggest higher muscle mass, it is very common 25 that obese individuals have also lower muscle mass than they pairs . The age-related 26 shifts in body composition that induce sarcopenia favor the development of obesity , which might explain the higher frequency of sarcopenic obesity among older adults. In this way, we believe the association we found between larger body mass and lower RMR in subgroup analysis is due to the lower muscle mass in heavier individuals. Furthermore, since our regression analyses did not show association with body mass, or fat mass, but a significant positive association with fat free mass difference between older and young adults and their RMR difference (r2=0.55), it reinforces that muscle mass plays a considerable role on aging RMR changes. Indirectly, our results suggest that therapies designed to increase muscle mass such as exercise training, protein or other types of supplementations could attenuate the reduction of RMR with age27,28. A limitation of our analysis was the sample overlapping in some control groups, 11 such as in the studies of Lührmann et al. and Alfonzo-González et al. 29. It led to an impression of larger sample number in younger control groups, but the number of older and young adults in each group were in fact very well balanced. 5 CONCLUSION RMR is progressively lower in older compared to younger adults, with a more prominent reduction in men than women. The main player in this process is the age- induced muscle loss. Future studies should investigate how much of this reduction can account for poor health conditions in older adults and whether interventions for increase muscle mass, such as resistance exercise could be a good strategy to oppose the natural changes. Brazilian Journal of Health Review, Curitiba, v.4, n.4, p.17867-17882 jul./aug. 2021
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