MET
Hepatocyte growth factor receptor precursor (EC 2.7.10.1) (HGF receptor) (HGF/SF receptor) (Proto-oncogene c-Met) (Scatter factor receptor) (SF receptor) (Tyrosine-protein kinase Met)
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We aimed to investigate associations of self-rated health with fruit and vegetable consumption (FVC) and physical activity (PA) among older cancer survivors. We used the 2017 Behavioral Risk Factor Surveillance System to identify cancer survivors ≥ 65 years (N = 2663). Self-reported FVC and PA were categorized as ordinal variables to approximate quartiles. Low general health (LGH) was defined as fair or poor self-rated health. A multivariable logistic regression treating LGH as the outcome was used to calculate adjusted odd ratios (aORs) and 95% confidence intervals (CIs) for FVC and PA. Restricted cubic spline depicted non-linear dose-response curves for FVC and PA. In comparative analysis, we used the same logistic regression and dose-response model to calculate ORs of FVC and PA in 73,134 people ≥ 65 years without cancer history. Overall, 470 (17.7%) survivors had LGH. Survivors' mean age was 73.3 years (SD = 5.2), 55.1% of them were female, and 95.4% self-reported as white. In cancer survivors, FVC was not associated with LGH (≥ 28 vs. < 14 times/week: aOR = 1.02, 95% CI = 0.75-1.39, p-trend = 0.50), whereas PA was inversely associated with LGH (≥ 30 vs. < 7 MET-hours/week: aOR = 0.55, 95% CI = 0.41-0.75, p-trend < 0.01). Dose-response curves demonstrated consistent association patterns. In comparative analysis, ORs of PA did not change substantially but we observed inverse association for FVC. An inverse association between PA and LGH was observed among older cancer survivors, but no significant association was obtained for FVC among them. Regular PA may maintain or indicate a favorable health in older cancer survivors, whereas impacts of FVC deserve further investigations.
Keywords
- Cancer survivorship
- Epidemiology
- Fruit and vegetable
- Gerontology
- Physical activity
Detailed catalog of lung cancer-associated gene mutations provides valuable information for lung cancer diagnosis and treatment. In China, there has never been a wide-ranging study cataloging lung cancer-associated gene mutations. This study aims to reveal a comprehensive catalog of lung cancer gene mutations in china, focusing on EGFR, ALK, KRAS, HER2, PIK3CA, MET, BRAF, HRAS, and CTNNB1 as major targets. Additionally, we also aim to correlate smoking history, gender, and age distribution and pathological types with various types of gene mutations. A retrospective data acquisition was conducted spanning 6 years (2013-2018) among all patients who underwent lung cancer surgeries not bronchial or percutaneous lung biopsy at three major tertiary hospitals. Finally, we identified 1,729 patients who matched our inclusion criteria. 1081 patients (62.49%) harbored EGFR mutation. ALK ([i]n[/i] = 42, 2.43%), KRAS ([i]n[/i] = 201, 11.62%), CTNNB1 ([i]n[/i] = 28, 1.62%), BRAF ([i]n[/i] = 31, 1.79%), PIK3CA ([i]n[/i] = 51, 2.95%), MET ([i]n[/i] = 14, 0.81%), HER2 ([i]n[/i] = 47, 2.72%), HRAS ([i]n[/i] = 3, 0.17%), and other genes([i]n[/i] = 232, 13.4%). Females expressed 55.38% vs. males 44.62% mutations. Among subjects with known smoking histories, 32.82% smokers, 67.15% non-smokers were observed. Generally, 51.80% patients were above 60 years vs. 48.20% in younger patients. Pathological types found includes LUADs 71.11%, SQCCs 1.68%, ASC 0.75%, LCC 0.58%, SCC 0.35%, ACC 0.17%, and SC 0.06%, unclear 25.19%. We offer a detailed catalog of the distribution of lung cancer mutations. Showing how gender, smoking history, age, and pathological types are significantly related to the prevalence of lung cancer in China.
Keywords
- China
- aging
- gene mutation
- lung cancer
- pathology
- tobacco smoking
Mitigating age-related disease and disability presents challenges. Physical activity (PA) may be influential for prolonging health and functioning, warranting characterization of its patterns over the life course in population-based data. With the availability of up to three self-reported assessments of past year leisure-time PA (LTPA) over multiple decades in 15,036 participants (26% African American; 55% women; mean baseline age=54; median follow-up=23 years) from the Atherosclerosis Risk in Communities (ARIC) Study sampled from four U.S. communities, race-sex-stratified trajectories of average weekly intensity (metabolic equivalent of task (MET)), duration (hours), and energy expenditure or volume (MET-h) of LTPA were developed from age 45 to 90 using joint models to accommodate expected non-ignorable attrition. Declines in weekly LTPA intensity, duration, and volume from age 70 to 90 were observed in white women (2.9 to 1.2 MET; 2.5 to 0.6 h; 11.1 to 2.6 MET-h), white men (2.5 to 1.0 MET; 3.5 to 1.8 h; 15.5 to 6.4 MET-h), African American women (2.5 to 2.4 MET; 0.8 to 0.1 h; 6.7 to 6.0 MET-h), and African American men (2.3 to 1.4 MET; 1.5 to 0.6 h; 8.0 to 2.3 MET-h). These data reveal population-wide shifts towards less active lifestyles in older adulthood.
Keywords
- exercise
- healthy aging
- physical activity
- retirement
- successful aging
In [i]Caenorhabditis elegans[/i], mutations in WDR-5 and other components of the COMPASS H3K4 methyltransferase complex extend lifespan and enable its inheritance. Here, we show that [i]wdr-5[/i] mutant longevity is itself a transgenerational trait that corresponds with a global enrichment of the heterochromatin factor H3K9me2 over twenty generations. In addition, we find that the transgenerational aspects of [i]wdr-5[/i] mutant longevity require the H3K9me2 methyltransferase MET-2, and can be recapitulated by removal of the putative H3K9me2 demethylase JHDM-1. Finally, we show that the transgenerational acquisition of longevity in [i]jhdm-1[/i] mutants is associated with accumulating genomic H3K9me2 that is inherited by their long-lived wild-type descendants at a subset of loci. These results suggest that heterochromatin facilitates the transgenerational establishment and inheritance of a complex trait. Based on these results, we propose that transcription-coupled H3K4me via COMPASS limits lifespan by encroaching upon domains of heterochromatin in the genome.
MeSH Terms
- Animals
- Caenorhabditis elegans
- Caenorhabditis elegans Proteins
- Heterochromatin
- Histone-Lysine N-Methyltransferase
- Histones
- Inheritance Patterns
- Jumonji Domain-Containing Histone Demethylases
- Longevity
- Lysine
- Methylation
- Mutation
Keywords
- C. elegans
- COMPASS
- aging
- chromatin
- chromosomes
- epigenetics
- gene expression
- genetics
- genomics
- heterochromatin
- transgenerational inheritance
Studies show that regular moderate to vigorous physical activity is associated with a lower risk of cardiovascular disease, certain cancers, and premature death, but few studies have examined associations of light-intensity physical activity (LPA) and mortality, especially among older adults. The aim of this study was to investigate the association of LPA with the risks of death from all causes, cancer, cardiovascular diseases, and respiratory diseases among older adults in the Cancer Prevention Study-II Nutrition Cohort (CPS-II NC). Analyses included 123,232 participants in CPS-II NC, among whom 46,829 died during follow-up (1993-2014). Cox proportional hazards regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI) for self-reported leisure time LPA associated with mortality. Engaging in little or no LPA (<3 metabolic equivalent [[[MET]]]-h/week) was associated with a 16% higher risk of all-cause mortality (HR 1.16, 95% CI 1.12-1.20) compared to engaging in some LPA (3 to <9 MET-h/week) after adjusting for moderate to vigorous physical activity. However, there was no evidence of a dose-response relationship. A statistically significant interaction with age suggested that more LPA was associated with a lower risk of respiratory disease mortality only among participants aged ≥70 years (21 vs. 3 to <9 MET-h/week, HR 0.78, 95% CI 0.66-0.91; pint = 0.003). In this prospective study of older adults, accumulating little/no leisure time LPA was associated with a higher risk of mortality. It is of substantial public health value to demonstrate the potential benefits of engaging in any activity, even if light in intensity, among older adults given the aging US population.
MeSH Terms
- Aged
- Cardiovascular Diseases
- Cohort Studies
- Exercise
- Female
- Follow-Up Studies
- Humans
- Leisure Activities
- Male
- Middle Aged
- Mortality
- Neoplasms
- Proportional Hazards Models
- Prospective Studies
- Respiratory Tract Diseases
- Risk Factors
- Surveys and Questionnaires
- United States
Keywords
- Aging
- Cancer prevention study
- Leisure time physical activity
- Light-intensity physical activity
Adults and older adults are recommended to engage in 150 minutes of moderate (MPA) to vigorous (VPA) aerobic physical activity (MVPA) per week, with the heuristic message of 3000 steps in 30 minutes (100 steps per minute [spm]). However, this message is based on adult populations, with a paucity of research on step-rate thresholds that correspond to absolute MVPA (moderate=3 metabolic equivalents [[[MET]]s], vigorous=6 METs) and relative MVPA (moderate=40% estimated MET , vigorous=60% estimated MET ) in older persons, who have lower stride lengths and a lower exercise capacity. Also, there is a need to consider the influence of anthropometric differences when quantifying the relationship between step rate and intensity-related physical activity. This study assessed absolute and relative MVPA step-rate thresholds and anthropometric factors (ie, height, leg length, and body mass index [BMI]) in older adults. Nineteen older adults (7 females; age 69 years, SD 2, BMI 26 kg/m , SD 4) completed a staged treadmill walking protocol: six minutes at 2.4, 3.2, 4.0, 5.6, and 6.4 km/h. Steps were manually counted and volume rate of oxygen consumed (VO ) was measured via indirect calorimetry. Aerobic fitness was estimated via the submaximal single-stage treadmill protocol. When BMI was considered, mixed effects modeling revealed absolute and relative MPA step-rate thresholds of 108 spm and 117 spm, respectively. Absolute and relative VPA corresponded to step rates of 135 spm and 132 spm, respectively. Neither height nor leg length improved the ability of the model to predict stepping cadence from METs. In general, older adults need to walk faster than 100 spm (ie, approximately 110 spm) to reach MPA and in excess of approximately 130 spm to achieve VPA, depending on BMI status. Health care professionals and researchers should adjust cadence-based recommendations for differences in BMI in their older patients and consider using relative intensity to most appropriately tailor their physical activity recommendations.
Keywords
- aging
- cadence
- physical activity intensity
- public health
- walking
Multimorbidity is an emerging public health priority. Physical activity (PA) is recommended as one of the main lifestyle behaviours, yet the benefits of PA for people with multimorbidity are unclear. We assessed the benefits of PA on mortality and life expectancy in people with and without multimorbidity. Using the UK Biobank dataset, we extracted data on 36 chronic conditions and defined multimorbidity as (a) 2 or more conditions, (b) 2 or more conditions combined with self-reported overall health, and (c) 2 or more top-10 most common comorbidities. Leisure-time PA (LTPA) and total PA (TPA) were measured by questionnaire and categorised as low (< 600 metabolic equivalent (MET)-min/week), moderate (600 to < 3000 MET-min/week), and high (≥ 3000 MET-min/week), while objectively assessed PA was assessed by wrist-worn accelerometer and categorised as low (4 min/day), moderate (10 min/day), and high (22 min/day) walking at brisk pace. Survival models were applied to calculate adjusted hazard ratios (HRs) and predict life expectancy differences. 491,939 individuals (96,622 with 2 or more conditions) had a median follow-up of 7.0 (IQR 6.3-7.6) years. Compared to low LTPA, for participants with multimorbidity, HR for mortality was 0.75 (95% CI 0.70-0.80) and 0.65 (0.56-0.75) in moderate and high LTPA groups, respectively. This finding was consistent when using TPA measures. Using objective PA, HRs were 0.49 (0.29-0.80) and 0.29 (0.13-0.61) in the moderate and high PA groups, respectively. These findings were similar for participants without multimorbidity. In participants with multimorbidity, at the age of 45 years, moderate and high LTPA were associated with an average of 3.12 (95% CI 2.53, 3.71) and 3.55 (2.34, 4.77) additional life years, respectively, compared to low LTPA; in participants without multimorbidity, corresponding figures were 1.95 (1.59, 2.31) and 1.85 (1.19, 2.50). Similar results were found with TPA. For objective PA, moderate and high levels were associated with 3.60 (- 0.60, 7.79) and 5.32 (- 0.47, 11.11) life years gained compared to low PA for those with multimorbidity and 3.88 (1.79, 6.00) and 4.51 (2.15, 6.88) life years gained in those without. Results were consistent when using other definitions of multimorbidity. There was an inverse dose-response association between PA and mortality. A moderate exercise is associated with a longer life expectancy, also in individuals with multimorbidity.
MeSH Terms
- Adult
- Aged
- Biological Specimen Banks
- Comorbidity
- Exercise
- Female
- Humans
- Life Expectancy
- Life Style
- Longitudinal Studies
- Male
- Middle Aged
- Mortality
- Motor Activity
- Multimorbidity
- Surveys and Questionnaires
- United Kingdom
Keywords
- Co-morbidity
- Life expectancy
- Mortality
- Multimorbidity
- Physical activity
- UK Biobank
A number of studies have shown that metformin can delay aging process and extend healthy lifespan in animals. However, its role in female reproductive lifespan is unclear. This study was aimed to explore the potential anti-aging effect of metformin on the ovary and its possible mechanisms. Female C57BL/6 mice of 27-week old were divided into two groups, the control group (CON) and metformin-treated group (MET). CON mice were fed ad libitum, while MET mice were fed on chows supplied with 100mg/kg metformin for half a year. Ovarian reserve and function were assessed by ovarian follicle counts, estrous cycle and sex hormones levels. The expressions of oxidized metabolites, such as 8-hydroxy-2´-deoxyguanosine (8-OHdG), 4-hydroxynonenal (4-HNE), nitrotyrosine (NTY), and ovarian aging associated proteins P16, SIRT1, p-rpS6 and Bcl2 were examined. The MET mice exhibited increased level of serum E2 hormone and higher percentage of regular estrous cycles after 6 months' feeding, compared to the CON mice. The amount of primordial and primary follicles and the expression of SIRT1 were significantly increased, but the levels of P16, 8-OHdG, 4-HNE and p-rpS6 were decreased in the MET mice. These results indicate that metformin can delay ovarian aging process, probably by inducing the expression of SIRT1 and reducing the oxidative damage.
MeSH Terms
- 8-Hydroxy-2'-Deoxyguanosine
- Aldehydes
- Animals
- Cellular Senescence
- Estradiol
- Estrous Cycle
- Female
- Hypoglycemic Agents
- Metformin
- Mice
- Ovarian Reserve
- Ovary
- Oxidative Stress
- Sirtuin 1
- Tyrosine
Keywords
- SIRT1
- metformin
- ovarian aging
- oxidative stress
The elevated methionine (MET) requirement of cancer cells is termed MET dependence and is possibly the only known general metabolic defect in cancer. Targeting MET by recombinant methioninase (rMETase) can arrest the growth of cancer cells in vitro and in vivo due to their elevated requirement for MET. rMETase can also potentiate chemotherapy drugs active in S phase due to the selective arrest of cancer cells in S/G phase during MET restriction (MR). We previously reported that rMETase, administrated by intraperitoneal injection (ip-rMETase), could inhibit tumor growth in mouse models of cancer including patient-derived orthotopic xenograft (PDOX) mouse models. We subsequently compared ip-rMETase and oral rMETase (o-rMETase) on a melanoma PDOX mouse model. o-rMETase was significantly more effective than ip-rMETase to inhibit tumor growth without overt toxicity. The combination of o-rMETase ip-rMETase was significantly more effective than either monotherapy and completely arrested tumor growth. Thus, o-rMETase is effective as an anticancer agent with the potential of clinical development for chronic cancer therapy as well as for cancer prevention. o-rMETase may also have potential as an antiaging agent for healthy people, since MR has been shown to extend the life span of a variety of different organisms.
MeSH Terms
- Administration, Oral
- Aged
- Aging
- Animals
- Carbon-Sulfur Lyases
- Female
- Humans
- Mice, Nude
- Neoplasms
- Recombinant Proteins
- Xenograft Model Antitumor Assays
Keywords
- Melanoma
- Methionine dependence
- Nude mice
- Oral administration
- Orthotopic
- PDOX
- Pyridoxal-L-phosphate
- Recombinant methioninase
Health behavior changes often require focusing on factors beyond the individual, particularly in low-income and underresourced areas. The purpose of this article was to assess associations between household structure and adult physical activity levels. Data were collected using Community Assessment for Public Health Emergency Response methodology to administer a household survey ([i]n[/i] = 100). Household structure was calculated from summing the number of adults (⩾18 years) and children (<18 years) reported living in the house. Physical activity was measured using the International Physical Activity Questionnaire-Short Form. Adults living in households with two or more adults reported more MET (metabolic equivalent of task) minutes of physical activity per week than adults from households with only one adult. Adults living in households with two or more adults were twice as likely to meet aerobic guidelines for physical activity compared to adults living in households with only adult. Findings suggest the need for developing ecologic approaches in low-income communities to increase social support for physical activity in adults.
Keywords
- African Americans minority health
- aging
- health disparities
- physical activity/exercise
This study aimed at investigating whether there is a continuous dose-response relationship between the amount of physical activity (PA) and longevity benefit. We evaluated the records of 23,257,723 Koreans age ≥20 yr who had undergone one biennial medical evaluation by the National Health Insurance Corporation. Participants with ≥20 min of vigorous or ≥30 min of moderate PA or walking were stratified into four groups: 0 d·wk; 1-3 d·wk; 4 to 5 d·wk; and 6-7 d·wk. After calculating total metabolic equivalent task-hours per week (MET·h·wk), we created eight categories of MET-hours per week (0, 0.1-4.9, 5.0-9.9, 10.0-14.9, 15.0-19.9, 20.0-24.9, 25.0-29.9, and ≥30.0). Multivariate Cox proportional hazard analyses were performed. A reverse J-shaped risk curve was observed, with the lowest mortality risk in the participants exercising 4 to 5 d·wk (reference). Participants who did not exercise at all and those who exercised with a PA frequency of 1 to 3 d·wk or 6 to 7 d·wk showed a significantly increased mortality risk compared with the reference group. When we repeated the Cox analysis among the 8 MET·h·wk categories with the participants reporting 20.0 to 24.9 MET·h·wk of PA as the reference group, we found that those with physical inactivity and 25.0-29.9 or ≥30.0 MET·h·wk of PA showed a higher mortality risk than the reference group. These relationships were persistently observed after adjustment for confounders. An appropriate amount of regular exercise in each specific type of PA was associated with the lowest risk of mortality. The inactive participants showed an increased mortality risk, and daily PA did not show any additional benefit in the mortality risk.
MeSH Terms
- Adult
- Aged
- Exercise
- Female
- Humans
- Longevity
- Male
- Metabolic Equivalent
- Middle Aged
- Mortality
- Republic of Korea
- Risk Reduction Behavior
- Surveys and Questionnaires
- Walking
Relatively little is known regarding the association between objective measures of physical function such as cardiorespiratory fitness (CRF) and cognitive function tests in healthy older adults. To evaluate the relationship between CRF and cognitive function in adults aged 55 and older. Between 2008 and 2017, 4,931 men and women underwent a comprehensive preventive physical exam at the Cooper Clinic in Dallas, Texas. CRF was determined by duration of a maximal treadmill exercise test. Cognitive function was evaluated with the Montreal Cognitive Assessment (MoCA). In a multivariate model, adjusted odds ratios with 95% confidence intervals for MoCA scores < 26 (i.e., cognitive impairment) were determined by using CRF as both a continuous and a categorical variable. The mean age of the sample was 61.0 ± 6.0 years; mean maximal MET values were 10.0 ± 2.2. Mean MoCA scores were 26.9 ± 2.2; 23.4% of the sample had MoCA scores indicative of cognitive impairment. The odds ratio for cognitive impairment was 0.93 (0.88-0.97) per 1-MET increment in CRF. When examined as a categorical variable, and using the lowest CRF quintile as the referent, there was a significantly reduced likelihood for cognitive impairment across the remaining ordered CRF categories (p trend = 0.004). The association between CRF and MoCA score in older adults suggests that meeting or exceeding public health guidelines for physical activity is likely to increase CRF in low fit individuals, maintain CRF in those with a moderate to high level of CRF, and thereby help to maintain cognitive function in healthy older adults.
MeSH Terms
- Aged
- Aging
- Cardiorespiratory Fitness
- Cognition
- Cognitive Dysfunction
- Exercise
- Exercise Test
- Female
- Humans
- Longitudinal Studies
- Male
- Mental Status and Dementia Tests
- Middle Aged
- Risk Factors
- Texas
Keywords
- Cardiorespiratory fitness
- Cognitive impairment
- Montreal cognitive assessment
Extension of mammalian health and life span has been achieved using various dietary interventions. We previously reported that restricting dietary methionine (MET) content extends life span only when growth hormone signaling is intact (no life span increase in GH deficiency or GH resistance). To understand the metabolic responses of altered dietary MET in the context of accelerated aging (high GH), the current study evaluated MET and related pathways in short-living GH transgenic (GH Tg) and wild-type mice following 8 weeks of restricted (0.16%), low (0.43%), or enriched (1.3%) MET consumption. Liver MET metabolic enzymes were suppressed in GH Tg compared to diet-matched wild-type mice. MET metabolite levels were differentially affected by GH status and diet. SAM:SAH ratios were markedly higher in GH Tg mice. Glutathione levels were lower in both genotypes consuming 0.16% MET but reduced in GH Tg mice when compared to wild type. Tissue thioredoxin and glutaredoxin were impacted by diet and GH status. The responsiveness to the different MET diets is reflected across many metabolic pathways indicating the importance of GH signaling in the ability to discriminate dietary amino acid levels and alter metabolism and life span.
MeSH Terms
- Adaptation, Physiological
- Animals
- Diet
- Glutathione
- Growth Hormone
- Liver
- Longevity
- Male
- Methionine
- Mice
- Mice, Transgenic
Keywords
- aging
- amino acid
- glutathione
- hormones
- metabolomics
- mice
Despite the rapid worldwide expansion of parks with outdoor fitness equipment (OFE), no objective data regarding the intensity of activity associated with using OFE are available. Hence, this study quantified the energy expenditure and intensity of physical activity by examining four outdoor fitness devices widely used by older adults and provides objective evidence-based intensity references for the Compendium of Physical Activities. Sixteen older adults (mean age: 70.7 ± 5.6 yr) equipped with a portable metabolic system for measuring energy expenditure and activity intensity completed tasks while walking or using four types of OFE. Descriptive statistics and repeated-measures ANOVA with the Bonferroni post hoc test were employed. The energy expenditure and activity intensity for using an air walker at tempos of 80, 100, and 120 bpm were 50.78 ± 14.76 (2.81 ± 0.85), 59.62 ± 14.23 (3.26 ± 0.82), and 65.62 ± 18.27 (3.55 ± 1.02) cal/kg/min (METs), respectively. The induced energy and intensity output values for a ski machine were 54.00 ± 14.31 (3.02 ± 0.87), 68.87 ± 22.74 (3.82 ± 1.35), and 74.55 ± 23.39 (4.05 ± 1.35) cal/kg/min (METs), at 80, 100, and 120 bpm, respectively. The energy output for a waist twister at 60 bpm was 38.43 ± 20.16 cal/kg/min (2.05 ± 1.15 METs), and that for a double arm stretch at 80 bpm was 31.05 ± 12.58 cal/kg/min (1.63 ± 0.70 METs). These findings indicate that activity on the ski machine and air walker could be considered to have moderate intensity, whereas the intensity of activity on the waist twister and double arm stretch was significantly lower than that for walking at either 3.2 km/h or 4 km/h and could be considered only light intensity. The MET values for the OFE were lower than those for similar indoor fitness equipment. The results of this study provide crucial implications for public health practices concerning the development of active living environments.
MeSH Terms
- Aged
- Aging
- Analysis of Variance
- Calorimetry
- Energy Metabolism
- Evidence-Based Medicine
- Exercise
- Exercise Test
- Female
- Health Promotion
- Humans
- Male
- Physical Fitness
- Walking
Hypoxia (i.e. oxygen deprivation) activates the hypoxia-signalling pathway, primarily via hypoxia-inducible transcription factors (HIF) for numerous target genes, which mediate angiogenesis, metabolism and coagulation, among other processes to try to replenish tissues with blood and oxygen. Hypoxia signalling dysregulation also commonly occurs during chronic inflammation. We sampled gingival tissues from rhesus monkeys (Macaca mulatta; 3-25 years old) and total RNA was isolated for microarray analysis. HIF1A, HIF1B and HIF2A were significantly different in healthy aged tissues, and both HIF1A and HIF3A were positively correlated with aging. Beyond these transcription factor alterations, analysis of patterns of gene expression involved in hypoxic changes in tissues showed specific increases in metabolic pathway hypoxia-inducible genes, whereas angiogenesis pathway gene changes were more variable in healthy aging tissues across the animals. With periodontitis, aging tissues showed decreases in metabolic gene expression related to carbohydrate/lipid utilization (GBE1, PGAP1, TPI1), energy metabolism and cell cycle regulation (IER3, CCNG2, PER1), with up-regulation of transcription genes and cellular proliferation genes (FOS, EGR1, MET, JMJD6) that are hypoxia-inducible. The potential clinical implications of these results are related to the epidemiological findings of increased susceptibility and expression of periodontitis with aging. More specifically the findings describe that hypoxic stress may exist in aging gingival tissues before documentation of clinical changes of periodontitis and, so, may provide an explanatory molecular risk factor for an elevated capacity of the tissues to express destructive processes in response to changes in the microbial biofilms characteristic of a more pathogenic microbial challenge.
MeSH Terms
- Age Factors
- Aging
- Animals
- Basic Helix-Loop-Helix Transcription Factors
- Gene Expression
- Hypoxia
- Hypoxia-Inducible Factor 1, alpha Subunit
- Macaca mulatta
- Mucous Membrane
- Periodontitis
- Signal Transduction
Keywords
- aging
- hypoxia
- mucosal tissues
- non-human primates
- periodontitis
Instructions for older adults regarding the intensity of walking may not elicit an intensity to infer health gains. We recorded the metabolic equivalents (METs) during a 1-mile walk using constant and predicted values of resting MET in older adults to establish walking guidelines for health promotion and participation. In a cross-sectional design study, participants (15 men, 10 women) walked 1-mile overground, in a wooden floored gymnasium, wearing the Cosmed K4b for measurement of energy expenditure. Constant or predicted values for resting MET were used to calculate the number of 1-mile walks to meet 450-750 MET∙min∙wk . Participants had MET values higher than 3 for both methods, with 29% and 64% of the participants higher than 6 for a constant and predicted MET value, respectively. The METs of the1-mile walk were (mean ± SD) 6 ± 1 and 7 ± 1 METs using constant and predicted resting MET,and similar for men (constant: 6 ± 1 METs; predicted: 7 ± 1 METs) and women (constant: 5±1METs; predicted: 6 ± 1 METs) (P > 0.05). Older adults that are instructed to walk 1-mile at a fast and constant pace meet the minimum required intensity for physical activity, and public health guidelines. Health professionals, that administer exercise, could encourage older adults to accumulate between six and nine 1-mile walks per week for health gains.
Keywords
- Aging
- Health promotion
- Metabolic equivalent
- One-mile walk
The physical demands of firefighting require both cardiovascular and muscular fitness, which both decline with age. While much has been published on age-related changes among male firefighters (FFs), data on female FFs are lacking. To describe cardiorespiratory fitness (CRF) and muscular fitness in a sample of female career FFs ranging in age from 25 to 60 years and determine whether ageing affects their achievement of the current recommended professional CRF standards of 12 metabolic equivalents (METs). Data were collected on female FFs over an 11-year period. A cross-sectional analysis using one-way analysis of variance with Bonferroni post hoc comparisons was used to compare age groups. There were 96 study participants. Maximum METs was significantly higher (P < 0.01) in the 25- to 34-year age group (14.6 ± 2.1) compared with the 35-44 age group (12.9 ± 2.0 METs) and the 45-54 age group (12.2 ± 1.8 METs, P < 0.001). While the mean values of all measured age groups met or exceeded the 12-MET profession standard, as many as one-third of FFs <45 years of age and 43% of FFs >45 years of age fell below the benchmark of 12 METs. Muscular fitness as measured by maximum number of push-ups, sit-ups and back endurance was not significantly different between age groups. Fire departments should recognize and take steps to ensure all female FFs maintain CRF and muscular fitness throughout their careers.
MeSH Terms
- Adult
- Aging
- California
- Cross-Sectional Studies
- Exercise Test
- Female
- Firefighters
- Humans
- Middle Aged
- Physical Fitness
Keywords
- Ageing
- cardiorespiratory fitness
- firefighters
- muscular fitness
- women
Links between physical activity and dementia are based primarily on cross-sectional data or studies with unsatisfactory follow-up. We leveraged three decades of follow-up from an established cohort to determine whether physical activity in midlife is associated with late-life cognition and dementia. The Johns Hopkins Precursors study (n = 646) enrolled participants from 1948-1964 and administered questions about physical activity, from which we calculated metabolic equivalents (MET h/day), and exercise from 1978-present. Cognitive tests were administered in 2008. Dementia was adjudicated through 2011. To characterize associations with midlife physical activity, we used linear regression for cognitive tests and Cox proportional hazards models for dementia onset. Models adjusted for age, sex, smoking, diabetes, and hypertension. No physical activity measure from 1978 was associated with late-life cognition or onset of dementia. Both MET h/day (β= 0.007, 95% CI: 0.002, 0.013) and regular exercise (β= 0.357, 95% CI: 0.202, 0.513) in 2006, however, were associated with better cognition in 2008. Findings from this 30-year cohort study that physical activity measured recently, but not in mid-life, is associated with late-life cognition fits with null findings from randomized trials and other observational studies with extensive follow-up. Cross-sectional findings may be misleading due to reverse causation.
MeSH Terms
- Age Factors
- Aged
- Aged, 80 and over
- Aging
- Cognition
- Cognition Disorders
- Cohort Studies
- Exercise
- Female
- Humans
- Linear Models
- Male
- Middle Aged
- Neuropsychological Tests
- Proportional Hazards Models
- Risk Factors
- Survival Analysis
Keywords
- Cognition
- dementia
- older adults
- physical activity
To examine prospective associations between changes in physical activity (PA) and changes in physical performance measures (PPMs) over 6 years in older women. Prospective cohort study. Forty clinical centers in the United States. Women aged 65 and older (mean age 69.8) enrolled in the Women's Health Initiative Clinical Trials with gait speed, timed chair stand, grip strength, and self-reported recreational PA data assessed at baseline (1993-98) and follow-up Years 1, 3, and 6 (N = 5,092). Mixed-effects linear regression models were used to determine the association between time-varying PA and change in each PPM. Potential interactions between time-varying PA and age (<70, ≥70) were also tested. Significan, dose-response associations between PA and improvements in all PPMs were observed over the 6 years of follow-up after adjusting for important covariates. High PA groups (≥1,200 metabolic equivalent (MET)-min/wk) had stronger grip strength (0.48 kg greater; P < .01), more chair stands (0.35 more; P < .001), and faster gait speeds (0.06 m/s faster; P < .001) than sedentary women (<100 MET-min/wk). Higher PA levels were associated with a greater increase in chair stands over time in women aged 70 and older (P < .001) than in those younger than 70 (P = .01). In postmenopausal women, maintaining high PA levels over time is associated with better lower extremity function. These data support the view that regular PA plays an important role in maintaining functional status during aging in older women.
MeSH Terms
- Aged
- Aged, 80 and over
- Aging
- Exercise
- Female
- Hand Strength
- Humans
- Lower Extremity
- Metabolic Equivalent
- Postmenopause
- Prospective Studies
- Self Report
- Time Factors
- United States
- Walking Speed
Keywords
- epidemiology
- mobility disability
- physical activity
- physical performance
- postmenopausal women
Cutaneous wounds are among the most common soft tissue injuries and are particularly hard to heal in aging. Caloric restriction (CR) is well documented to extend longevity; pharmacologically, profound rejuvenative effects of CR mimetics have been uncovered, especially metformin (MET), resveratrol (RSV), and rapamycin (RAPA). However, locally applied impacts and functional differences of these agents on wound healing remain to be established. Here, we discovered that chronic topical administration of MET and RSV, but not RAPA, accelerated wound healing with improved epidermis, hair follicles, and collagen deposition in young rodents, and MET exerted more profound effects. Furthermore, locally applied MET and RSV improved vascularization of the wound beds, which were attributed to stimulation of adenosine monophosphate-activated protein kinase (AMPK) pathway, the key mediator of wound healing. Notably, in aged skin, AMPK pathway was inhibited, correlated with impaired vasculature and reduced healing ability. As therapeutic approaches, local treatments of MET and RSV prevented age-related AMPK suppression and angiogenic inhibition in wound beds. Moreover, in aged rats, rejuvenative effects of topically applied MET and RSV on cell viability of wound beds were confirmed, of which MET showed more prominent anti-aging effects. We further verified that only MET promoted wound healing and cutaneous integrity in aged skin. These findings clarified differential effects of CR-based anti-aging pharmacology in wound healing, identified critical angiogenic and rejuvenative mechanisms through AMPK pathway in both young and aged skin, and unraveled chronic local application of MET as the optimal and promising regenerative agent in treating cutaneous wound defects.
MeSH Terms
- AMP-Activated Protein Kinases
- Acetyl-CoA Carboxylase
- Administration, Cutaneous
- Aging
- Animals
- Cyclin D1
- Cyclin-Dependent Kinase Inhibitor p16
- Enzyme Activation
- Female
- Gene Expression Regulation
- Metformin
- Mice
- Neovascularization, Physiologic
- Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
- Rats
- Rats, Sprague-Dawley
- Resveratrol
- Ribosomal Protein S6 Kinases
- Sirolimus
- Skin
- Skin Aging
- Stilbenes
- Tumor Suppressor Protein p53
- Wound Healing
- Wounds, Nonpenetrating
Keywords
- AMPK pathway
- aged skin
- anti-aging pharmacology
- metformin
- vascularization
- wound healing
The absorption and fluorescence properties of the metabolomic (MET), water-soluble and urea-soluble protein fractions from the middle-age, aged, and cataractous human lenses have been measured. At 280nm and 300nm the major lens absorbers are crystallins, which absorb more than 90% of light in the UV-B region (280-315nm). In middle-aged lenses, the absorption at 360nm is mostly provided by UV filters contained in the MET fraction. With aging, and especially with the cataract development, the absorption of MET fraction in UV-A region (315-400nm) decreases due to the drop of the UV filter concentration, while the absorption of protein fractions increases due to the accumulation of post-translational modifications. Consequently, the contribution of the MET fraction into the total lens absorption at 360nm decays from 63% in middle-aged lenses to 25% in aged lenses to 3% in cataractous lenses. The fluorescence yield of the MET fraction from cataractous lenses also significantly increases. Therefore, the protection of the lens tissue against UV radiation in aged and cataractous lenses weakens: the absorption of UV-A light is mostly provided by modified crystallins and non-UV-filter metabolites, which are photochemically more active than the UV filters. The obtained data indicate that the aged and cataractous human lenses are more vulnerable to UV-A light than the middle-aged lenses.
MeSH Terms
- Adult
- Aged
- Aged, 80 and over
- Aging
- Cataract
- Female
- Humans
- Lens, Crystalline
- Male
- Middle Aged
- Optical Phenomena
- Ultraviolet Rays
Keywords
- Absorption
- Cataract
- Fluorescence
- Human lens
This study examined a programme of pre-conditioning exercise with subsequent high intensity interval training (HIIT) on blood pressure, echocardiography, cardiac strain mechanics and maximal metabolic (MET) capacity in sedentary (SED) aging men compared with age matched masters athletes (LEX). Using a STROBE compliant observational design, 39 aging male participants (SED; n=22, aged 62.7±5.2yrs) (LEX; n=17, aged=61.1±5.4yrs) were recruited to a study that necessitated three distinct assessment phases; enrolment (Phase A), following pre-conditioning exercise in SED (Phase B), then following 6weeks of HIIT performed once every five days by both groups before reassessment (Phase C). Hemodynamic, echocardiographic and cardiac strain mechanics were obtained at rest and maximal cardiorespiratory and chronotropic responses were obtained at each measurement phase. The training intervention improved systolic, mean arterial blood pressure, rate pressure product and heart rate reserve (each P<0.05) in SED and increased MET capacity in both SED and LEX (P<0.01) which was amplified by HIIT. Echocardiography and cardiac strain measures were unremarkable apart from trivial increase to intra-ventricular septum diastole (IVSd) (P<0.05) and decrease to left ventricular internal dimension diastole (LVId) (P<0.05) in LEX following HIIT. A programme of preconditioning exercise with HIIT induces clinically relevant improvements in blood pressure, rate pressure product and encourages recovery of heart rate reserve in SED, while improving maximal MET capacity in both SED and LEX without inducing any pathological cardiovascular remodeling. These data add to the emerging repute of HIIT as a safe and promising exercise prescription to improve cardiovascular function and metabolic capacity in sedentary aging.
MeSH Terms
- Aged
- Blood Pressure
- Heart Rate
- High-Intensity Interval Training
- Humans
- Male
- Middle Aged
- Oxygen Consumption
- Sedentary Behavior
Keywords
- Aging
- Blood pressure
- Cardiac structure
- Cardiovascular function
- High intensity interval training (HIIT)
Higher levels of physical activity are associated with a lower risk of cardiovascular events. Nevertheless, there is debate on the dose-response relationship of exercise and cardiovascular disease outcomes and whether high volumes of exercise may accelerate coronary atherosclerosis. We aimed to determine the relationship between lifelong exercise volumes and coronary atherosclerosis. Middle-aged men engaged in competitive or recreational leisure sports underwent a noncontrast and contrast-enhanced computed tomography scan to assess coronary artery calcification (CAC) and plaque characteristics. Participants reported lifelong exercise history patterns. Exercise volumes were multiplied by metabolic equivalent of task (MET) scores to calculate MET-minutes per week. Participants' activity was categorized as <1000, 1000 to 2000, or >2000 MET-min/wk. A total of 284 men (age, 55±7 years) were included. CAC was present in 150 of 284 participants (53%) with a median CAC score of 35.8 (interquartile range, 9.3-145.8). Athletes with a lifelong exercise volume >2000 MET-min/wk (n=75) had a significantly higher CAC score (9.4 [interquartile range, 0-60.9] versus 0 [interquartile range, 0-43.5]; [i]P[/i]=0.02) and prevalence of CAC (68%; adjusted odds ratio [OR ]=3.2; 95% confidence interval [CI], 1.6-6.6) and plaque (77%; OR =3.3; 95% CI, 1.6-7.1) compared with <1000 MET-min/wk (n=88; 43% and 56%, respectively). Very vigorous intensity exercise (≥9 MET) was associated with CAC (OR =1.47; 95% CI, 1.14-1.91) and plaque (OR =1.56; 95% CI, 1.17-2.08). Among participants with CAC>0, there was no difference in CAC score ([i]P[/i]=0.20), area ([i]P[/i]=0.21), density ([i]P[/i]=0.25), and regions of interest ([i]P[/i]=0.20) across exercise volume groups. Among participants with plaque, the most active group (>2000 MET-min/wk) had a lower prevalence of mixed plaques (48% versus 69%; OR =0.35; 95% CI, 0.15-0.85) and more often had only calcified plaques (38% versus 16%; OR =3.57; 95% CI, 1.28-9.97) compared with the least active group (<1000 MET-min/wk). Participants in the >2000 MET-min/wk group had a higher prevalence of CAC and atherosclerotic plaques. The most active group, however, had a more benign composition of plaques, with fewer mixed plaques and more often only calcified plaques. These observations may explain the increased longevity typical of endurance athletes despite the presence of more coronary atherosclerotic plaque in the most active participants.
MeSH Terms
- Athletes
- Coronary Artery Disease
- Exercise
- Humans
- Longevity
- Male
- Middle Aged
- Single-Blind Method
- Time Factors
- Tomography, X-Ray Computed
Keywords
- atherosclerosis
- computed tomography angiography
- coronary vessels
- exercise
The principal objective was to determine the extent to which physical activity (PA) accounts for differences in leukocyte telomere length (LTL) in a large random sample of U.S. adults. Another purpose was to assess the extent to which multiple demographic and lifestyle covariates affect the relationship between PA and LTL. A total of 5823 adults from the National Health and Nutrition Examination Survey (NHANES 1999-2002) were studied cross-sectionally. Employing the quantitative polymerase chain reaction method, LTL was compared to standard reference DNA. PA was indexed using MET-minutes using self-reported frequency, intensity, and duration of participation in 62 physical activities. Covariates were controlled statistically. Telomeres were 15.6 base pairs shorter for each year of chronological age (F=723.2, P<0.0001). PA was inversely related to LTL after adjusting for all the covariates (F=8.3, P=0.0004). Telomere base pair differences between adults with High activity and those in the Sedentary, Low, and Moderate groups were 140, 137, and 111, respectively. Adults with High activity were estimated to have a biologic aging advantage of 9years (140 base pairs÷15.6) over Sedentary adults. The difference in cell aging between those with High and Low activity was also significant, 8.8years, as was the difference between those with High and Moderate PA (7.1years). Overall, PA was significantly and meaningfully associated with telomere length in U.S. men and women. Evidently, adults who participate in high levels of PA tend to have longer telomeres, accounting for years of reduced cellular aging compared to their more sedentary counterparts.
MeSH Terms
- Adult
- Aged
- Aged, 80 and over
- Cellular Senescence
- Cross-Sectional Studies
- Exercise
- Female
- Humans
- Leukocytes
- Male
- Middle Aged
- Nutrition Surveys
- Self Report
- Telomere
Keywords
- Cell aging
- Exercise
- NHANES
- Oxidative stress
- Physical activity
- Telomeres
Advanced Glycation End products (AGEs) are implicated in aging process. Thus, reducing AGEs by using glycation inhibitors may help in attenuating the aging process. In this study using Saccharomyces cerevisiae yeast system, we show that Aminoguanidine (AMG), a well-known glycation inhibitor, decreases the AGE modification of proteins in non-calorie restriction (NR) (2% glucose) and extends chronological lifespan (CLS) similar to that of calorie restriction (CR) condition (0.5% glucose). Proteomic analysis revealed that AMG back regulates the expression of differentially expressed proteins especially those involved in mitochondrial respiration in NR condition, suggesting that it switches metabolism from fermentation to respiration, mimicking CR. AMG induced back regulation of differentially expressed proteins could be possibly due to its chemical effect or indirectly by glycation inhibition. To delineate this, Metformin (MET), a structural analog of AMG and a mild glycation inhibitor and Hydralazine (HYD), another potent glycation inhibitor but not structural analog of AMG were used. HYD was more effective than MET in mimicking AMG suggesting that glycation inhibition was responsible for restoration of differentially expressed proteins. Thus glycation inhibitors particularly AMG, HYD and MET extend yeast CLS by reducing AGEs, modulating the expression of proteins involved in mitochondrial respiration and possibly by scavenging glucose. This study reports the role of glycation in aging process. In the non-caloric restriction condition, carbohydrates such as glucose promote protein glycation and reduce CLS. While, the inhibitors of glycation such as AMG, HYD, MET mimic the caloric restriction condition by back regulating deregulated proteins involved in mitochondrial respiration which could facilitate shift of metabolism from fermentation to respiration and extend yeast CLS. These findings suggest that glycation inhibitors can be potential molecules that can be used in management of aging.
MeSH Terms
- Cell Respiration
- Chronobiology Phenomena
- Gene Expression Regulation, Fungal
- Glycation End Products, Advanced
- Guanidines
- Mitochondria
- Saccharomyces cerevisiae
Keywords
- Aging
- Glucose
- Glycation
- Mass spectrometry
- Proteomics
Compared with older adults, emerging adults (18-29 years old) entering treatment typically have less severe alcohol use consequences. Also, their unique clinical presentations (e.g., modest initial abstinence motivation) and developmental contexts (e.g., drinking-rich social networks) may make a straightforward implementation of treatments developed for adults less effective. Yet, this has seldom been examined empirically. This study was a secondary analysis of Project MATCH (Matching Alcoholism Treatments to Client Heterogeneity) data examining (a) overall differences between emerging adults and older adults (≥30 years old) on outcomes during treatment and at 1-year follow-up, and (b) whether emerging adults had poorer outcomes on any of the three Project MATCH treatments in particular. Participants were 267 emerging adults and 1,459 older adults randomly assigned to individually delivered cognitive-behavioral therapy (CBT), motivational enhancement therapy (MET), or 12-step facilitation (TSF). Multilevel growth curve models tested differences on percentage of days abstinent (PDA) and drinks per drinking day (DDD) by age group and treatment assignment. During treatment, compared with older adults, emerging adults reported more DDD but similar PDA. Further, emerging adults assigned to TSF had less PDA and more DDD than emerging adults and older adults assigned to CBT or MET during treatment (i.e., emerging adults in TSF has poorer outcomes initially), but this matching effect was not evident at 1-year follow-up. This study is among the first to test age group differences across three psychosocial interventions shown to be efficacious treatments for alcohol use disorder. Although emerging adults generally did as well as their older counterparts, they may require a more developmentally sensitive approach to bolster TSF effects during treatment.
MeSH Terms
- Adolescent
- Adult
- Aging
- Alcohol Drinking
- Alcoholism
- Cognitive Behavioral Therapy
- Female
- Humans
- Male
- Motivational Interviewing
- Self Care
- Treatment Outcome
- Young Adult
The beneficial effect of physical activity on reducing hip fracture risk has been supported in many previous studies. The present cohort study explores the relationship between total daily physical activity expressed as MET-hour/day and hip fracture risk among men over 50 years of age and postmenopausal women (n=22,836). Associations between self-reported hip fracture incidence and total daily physical activity and selected lifestyle factors were assessed using Cox proportional hazard regression. In gender-specific multivariable models, total activity above average (≥ 51 MET-hours per day for men, ≥ 48 MET-hours per day for women) compared to those with sedentary lifestyle (< 40 MET-hours per day) reduced the risk of hip fracture by 60% among men (HR=0.40, 95%CI: 0.23-0.70) (Ptrend=0.002) and 48% among women (HR=0.52, 95%CI: 0.32-0.84) (Ptrend=0.01). Our findings suggest that a moderate level of physical activity and avoiding a sedentary lifestyle can reduce the risk of hip fracture among the elderly.
Keywords
- Fractures
- aging
- physical activity
- sedentary lifestyle
Previous research suggests that older persons show cognitive deficits in standardized laboratory tests, but not in more natural tests such as the Multiple Errands Task (MET). The absence of deficits in the latter tests has been attributed to the compensation of deficits by strategies based on life-long experience. To scrutinize this view, we primed older participants with positive or negative stereotypes about old age before administering MET. We found that compared to unprimed controls, priming with positive age stereotypes reduced the number of errors without changing response times, while priming with negative stereotypes changed neither errors not response times. We interpret our findings as evidence that positive age priming improved participants' cognitive functions while leaving intact their experience-based compensation, and that negative age priming degraded participants' cognitive functions which, however, was balanced by an even stronger experience-based compensation.
MeSH Terms
- Activities of Daily Living
- Aged
- Aged, 80 and over
- Aging
- Cognition
- Cognition Disorders
- Female
- Humans
- Male
- Middle Aged
- Reaction Time
- Stereotyping
"Metabolic Equivalent" (MET) represents a standard amount of oxygen consumed by the body under resting conditions, and is defined as 3.5 mL O₂/kg × min or ~1 kcal/kg × h. It is used to express the energy cost of physical activity in multiples of MET. However, universal application of the 1-MET standard was questioned in previous studies, because it does not apply well to all individuals. Height, weight and resting metabolic rate (RMR, measured by indirect calorimetry) were measured in adolescent males (n = 50) and females (n = 50), women during pregnancy (gestation week 35-41, n = 46), women 24-53 weeks postpartum (n = 27), and active men (n = 30), and were compared to values predicted by the 1-MET standard. The RMR of adolescent males (1.28 kcal/kg × h) was significantly higher than that of adolescent females (1.11 kcal/kg × h), with or without the effects of puberty stage and physical activity levels. The RMR of the pregnant and post-pregnant subjects were not significantly different. The RMR of the active normal weight (0.92 kcal/kg × h) and overweight (0.89 kcal/kg × h) adult males were significantly lower than the 1-MET value. It follows that the 1-MET standard is inadequate for use not only in adult men and women, but also in adolescents and physically active men. It is therefore recommended that practitioners estimate RMR with equations taking into account individual characteristics, such as sex, age and Body Mass Index, and not rely on the 1-MET standard.
MeSH Terms
- Adolescent
- Adult
- Aging
- Basal Metabolism
- Body Mass Index
- Child
- Energy Metabolism
- Exercise
- Female
- Humans
- Lactation
- Male
- Overweight
- Oxygen Consumption
- Postpartum Period
- Pregnancy
- Pregnancy Trimester, Third
- Reproducibility of Results
- Sex Characteristics
- Switzerland
- Thinness
- Young Adult
Keywords
- active men
- adolescents
- metabolic equivalent
- physical activity
- pregnant women
- resting metabolic rate
This study explored the effect of high mental effort training (MET) and conventional strength training (CST) on increasing voluntary muscle strength and brain signal associated with producing maximal muscle force in healthy aging. Twenty-seven older adults (age: 75 ± 7.9 yr, 8 women) were assigned into 1 of 3 groups: MET group-trained with low-intensity (30% maximal voluntary contraction [MVC]) physical exercise combined with MET, CST group-trained with high-intensity muscle contractions, or control (CTRL) group-no training of any kind. MET and CST lasted for 12 weeks (5 sessions/week). The participants' elbow flexion strength of the right arm, electromyography (EMG), and motor activity-related cortical potential (MRCP) directly related to the strength production were measured before and after training. The CST group had the highest strength gain (17.6%, P <0.001), the MET group also had significant strength gain (13.8%, P <0.001), which was not statistically different from that of the CST group even though the exercise intensity for the MET group was only at 30% MVC level. The CTRL group did not have significant strength changes. Surprisingly, only the MET group demonstrated a significant augmentation in the MRCP (29.3%, P <0.001); the MRCP increase in CST group was at boarder-line significance level (12.11%, P = 0.061) and that for CTRL group was only 4.9% (P = 0.539). These results suggest that high mental effort training combined with low-intensity physical exercise is an effective method for voluntary muscle strengthening and this approach is especially beneficial for those who are physically weak and have difficulty undergoing conventional strength training.
MeSH Terms
- Aged
- Aging
- Electromyography
- Exercise
- Female
- Humans
- Motor Skills
- Muscle Contraction
- Muscle Strength
- Resistance Training
No study has explored the effect of yoga on cognitive decline and resting-state functional connectivity. This study explored the relationship between performance on memory tests and resting-state functional connectivity before and after a yoga intervention versus active control for subjects with mild cognitive impairment (MCI). Participants ( ≥ 55 y) with MCI were randomized to receive a yoga intervention or active "gold-standard" control (i.e., memory enhancement training (MET)) for 12 weeks. Resting-state functional magnetic resonance imaging was used to map correlations between brain networks and memory performance changes over time. Default mode networks (DMN), language and superior parietal networks were chosen as networks of interest to analyze the association with changes in verbal and visuospatial memory performance. Fourteen yoga and 11 MET participants completed the study. The yoga group demonstrated a statistically significant improvement in depression and visuospatial memory. We observed improved verbal memory performance correlated with increased connectivity between the DMN and frontal medial cortex, pregenual anterior cingulate cortex, right middle frontal cortex, posterior cingulate cortex, and left lateral occipital cortex. Improved verbal memory performance positively correlated with increased connectivity between the language processing network and the left inferior frontal gyrus. Improved visuospatial memory performance correlated inversely with connectivity between the superior parietal network and the medial parietal cortex. Yoga may be as effective as MET in improving functional connectivity in relation to verbal memory performance. These findings should be confirmed in larger prospective studies.
MeSH Terms
- Brain
- Cognitive Dysfunction
- Functional Neuroimaging
- Humans
- Learning
- Magnetic Resonance Imaging
- Memory
- Neural Pathways
- Neuropsychological Tests
- Pilot Projects
- Yoga
Keywords
- Aging
- cognitive decline
- memory training
- mild cognitive impairment
- mind-body
- older adults
- subjective memory complaints
- yoga
Retirement is a major life transition which may affect lifestyle. The aim of this study is to examine within-individual changes in physical activity during the transition from full-time work to retirement. The study population consisted of 9,488 Finnish public-sector employees who retired in 2000-2011 and who reported their leisure-time and commuting physical activity before and after retirement. On average, participants provided data at 3.6 (of the four) repeat examinations during 10 years before and 10 years after the retirement. Physical activity was self-reported and was expressed as weekly metabolic equivalent task (MET) hours. Generalized estimating equations were used to examine physical activity trajectories around retirement. Among participants entering to statutory retirement physical activity first increased by 1.81 MET-hours (95% confidence interval [CI] 1.20 to 2.42) during 4-year retirement transition, but then decreased by -1.80 MET hours (95% CI -2.83 to -0.79) during the subsequent post-retirement period. Older retirement age, higher occupational status and fewer chronic diseases were associated with greater increase in physical activity during transition to statutory retirement. Statutory retirement appears to be associated with a temporary increase in physical activity. Future research should examine ways to maintain the increased activity level after retirement.
MeSH Terms
- Aged
- Cohort Studies
- Employment
- Exercise
- Female
- Humans
- Leisure Activities
- Life Style
- Male
- Metabolic Equivalent
- Middle Aged
- Motor Activity
- Retirement
- Self Report
- Transportation
- Work
Keywords
- Aging
- Cohort Study
- Physical activity
- Retirement
The purpose of the study was to evaluate the accuracy of direct observation (DO) to estimate MET level and intensity category during laboratory-based and free-living activity in older adults. Older adults engaged in unstructured laboratory and free-living activity. Participants wore a portable metabolic system to measure energy expenditure and were directly observed. DO recorded MET-level point estimates. 32,401 in-laboratory and 87,715 free-living data points (9 participants, 67% male, 71.0 ± 6.9 years, 27.1 ± 4.3 kg·m ) were included in final analysis. Results revealed 45.4% of in-laboratory and 61.1% of free-living mean DO activities fell within 0.5 METs of the measured MET values. DO accurately classified intensity category 45.0% of the time in-laboratory and 50.9% of free-living observations. DO-estimated activity cost resulted in low point estimate accuracy however there was low variability between the mean measured and estimated METs. This suggests, dependent on the desired outcome, DO could provide a viable option for activity assessment, however, the low point estimate accuracy presents a need for further research to continue to refine the approach to increase accuracy.
MeSH Terms
- Aged
- Body Mass Index
- Energy Metabolism
- Exercise
- Female
- Geriatric Assessment
- Humans
- Male
- Observation
Keywords
- aging
- measurement
- sedentary behavior
Previous research demonstrates that both physical activity and multimorbidity are associated with cognitive function. However, the extent to which physical activity may moderate the relationship between multimorbidity and cognitive function has not been thoroughly evaluated. Data from the 1999-2002 NHANES were used (60 years; N = 2157). A multimorbidity index variable was created based on physician diagnosis of a multitude of chronic diseases. Physical activity was self-reported and cognitive function was evaluated from the digit symbol substitution test. Multimorbidity was inversely associated with cognitive function for the unadjusted and adjusted models. However, generally, multimorbidity was no longer associated with cognitive function for the majority of older adults who achieved the minimum recommended physical activity level (≥2000 MET-min-month), as issued by the United States Department of Health and Human Services. In this national sample of older adults, there was some evidence to suggest that physical activity moderates the relationship between multimorbidity and cognitive function.
MeSH Terms
- Aged
- Aged, 80 and over
- Aging
- Chronic Disease
- Cognition
- Comorbidity
- Female
- Health Status
- Humans
- Male
- Middle Aged
- Motor Activity
- Nutrition Surveys
- Retrospective Studies
- United States
Keywords
- Chronic disease
- Epidemiology
- Executive function
- Health
Given the aging population and prevalence of sedentary behaviour in the USA, we investigated the impact of differences in exercise capacity associated with age on long-term outcomes. We derived fitness-associated 'biologic age' as a tool to encourage positive lifestyle changes. This retrospective cohort study included 57085 patients without established coronary artery disease or heart failure (median age 53 years, 49% women, 29% black) who underwent clinically-referred treadmill stress testing at the Henry Ford Health System from 1991 to 2009. Patients were followed for 10.4±5 and 5.4±4 years for all-cause mortality and myocardial infarction (MI), respectively. We calculated hazard ratios associated with exercise capacity by age deciles using Cox regression models, adjusting for demographic and haemodynamic data, medical history, and medication use. Fitness-associated 'biologic age' was derived as the chronologic age with equivalent mortality or MI risk. There were 6356 deaths and 1646 MIs during follow-up. Exercise capacity declined with increasing age. Higher exercise capacity was strongly associated with greater survival, with per-MET HR ranging from 0.82 (95% CI 0.78 to 0.86) in patients under 40 years of age, to 0.88 (95% CI 0.87 to 0.90) in those over 70 years of age. Biologic age varied markedly-up to three decades-within each age decile, and was a stronger predictor of mortality (C-statistic 0.81 vs 0.77) and MI (C-statistic 0.72 vs 0.68) than chronologic age. Higher exercise capacity remained a powerful predictor of survival despite lower average exercise capacity at older ages, reinforcing its importance in patients of all ages. Fitness-associated biologic age was a stronger predictor of survival than chronologic age, and may be a useful clinical tool for facilitating patient discussions regarding the impact of exercise capacity on long-term risk.
MeSH Terms
- Adult
- Age Factors
- Aged
- Aging
- Cause of Death
- Exercise Tolerance
- Female
- Follow-Up Studies
- Geriatric Assessment
- Humans
- Male
- Middle Aged
- Myocardial Infarction
- Physical Fitness
- Prognosis
- Retrospective Studies
- Survival Rate
- Time Factors
- United States
We aimed to verify whether different levels of training performed regularly and voluntarily for many years could have an impact on one of the main issues of immunosenescence: the poor response to vaccines. We recruited 61 healthy elderly men (65-85 years old), 23 with a moderate training (MT) lifestyle (for 17.0 ± 3.2 years), 22 with an intense training (IT) lifestyle (for 25.9 ± 3.4 years), and 16 without a training lifestyle (NT). Fitness was evaluated through the IPAQ and VO2max consumption. The participants were evaluated regarding cognitive aspects, nutritional status, depression, and quality of life. Antibody titers were determined by hemagglutination inhibition assay prior to influenza vaccination and at 6 weeks and 6 months post-vaccination. Strains used were B, H3N2, and H1N1. Our groups were matched for most characteristics, except for those directly influenced by their lifestyles, such as BMI, VO2max, and MET. In general, MT and IT elderly men showed significantly higher antibody titers to the three vaccine strains post-vaccination than NT elderly men. There were also higher titers against B and H1N1 strains in the trained groups before vaccination. Additionally, there were higher proportions of seroprotected (titers ≥1:40) individuals in the pooled trained groups both at 6 weeks (B and H3N2, p < 0.05) and 6 months (H1N1, p < 0.05; B, p = 0.07). There were no significant differences between the MT and IT groups. Either a moderate or an intense training is associated with stronger and longstanding antibody responses to the influenza vaccine, resulting in higher percentages of seroprotected individuals.
MeSH Terms
- Aged
- Aged, 80 and over
- Aging
- Antibodies, Viral
- Antibody Formation
- Cross-Sectional Studies
- Exercise
- Hemagglutination Inhibition Tests
- Humans
- Influenza Vaccines
- Influenza, Human
- Life Style
- Male
Keywords
- Antibody response
- Exercise
- Influenza
- Lifestyle
- Vaccine
Extending mammalian health span and life span has been achieved under a variety of dietary restriction protocols. Reducing the intake of a specific amino acid has also been shown to extend health and longevity. We recently reported that methionine (MET) restriction is not effective in life span extension in growth hormone (GH) signaling mutants. To better understand the apparent necessity of GH in the 'sensing' of altered dietary MET, the current study was designed to evaluate MET and glutathione (GSH) metabolism (as well as other pathways) in long-living GH-deficient Ames dwarf and wild-type mice following 8 weeks of restricted (0.16%), low (0.43%), or enriched (1.3%) dietary MET consumption. Metabolite expression was examined in liver tissue, while gene and protein expression were evaluated in liver, kidney, and muscle tissues. Body weight was maintained in dwarf mice on the MET diets, while wild-type mice on higher levels of MET gained weight. Liver MET levels were similar in Ames mice, while several MET pathway enzymes were elevated regardless of dietary MET intake. Transsulfuration enzymes were also elevated in Ames mice but differences in cysteine levels were not different between genotypes. Dwarf mice maintained higher levels of GSH on MET restriction compared to wild-type mice, while genotype and diet effects were also detected in thioredoxin and glutaredoxin. MET restriction increased transmethylation in both genotypes as indicated by increased S-adenosylmethionine (SAM), betaine, and dimethylglycine. Diet did not impact levels of glycolytic components, but dwarf mice exhibited higher levels of key members of this pathway. Coenzyme A and measures of fatty acid oxidation were elevated in dwarf mice and unaffected by diet. This component analysis between Ames and wild-type mice suggests that the life span differences observed may result from the atypical MET metabolism and downstream effects on multiple systems. The overall lack of responsiveness to the different diets is well reflected across many metabolic pathways in dwarf mice indicating the importance of GH signaling in the ability to discriminate dietary amino acid levels.
Keywords
- Aging
- Ames mice
- Amino acids
- Longevity
- Metabolomics
The determinants of insulin-associated weight gain in type 2 diabetes mellitus (T2DM) are partly unknown. Therefore, we conducted a prospective study to identify predictors of insulin-associated weight gain. In patients with T2DM, we assessed physical activity by accelerometry and measured diabetes-related distress by questionnaires before and 6 and 12 months after starting insulin therapy. Glycemic control (HbA1c) and insulin dose were monitored. After 12 months of insulin therapy, mean body weight had increased by 3.0 ± 2.5 kg (P < 0.001). The drop in HbA1c was correlated with insulin-associated weight gain. With the use of a multiple linear regression model, a cluster of variables was identified that significantly related to weight gain. Diabetes-related distress, initial insulin dose, and the increase of insulin dose during the course of the study as well as age appeared to be important predictors of weight gain after initiation of insulin therapy. Physical activity (measured as MET) decreased from 1.40 ± 0.04 at baseline to 1.32 ± 0.04 MET (P < 0.05) but was not significantly related to weight changes. Diabetes-related distress, initial and titration of insulin dose, and age all significantly predict insulin-associated weight gain. After the initiation of insulin therapy, physical activity decreased significantly, but this did not determine weight gain over the first 12 months. Our study findings may have clinical implications.
MeSH Terms
- Adult
- Aged
- Aging
- Body Weight
- Diabetes Mellitus, Type 2
- Dose-Response Relationship, Drug
- Female
- Follow-Up Studies
- Glycated Hemoglobin A
- Humans
- Hypoglycemic Agents
- Insulin
- Linear Models
- Male
- Middle Aged
- Motor Activity
- Predictive Value of Tests
- Prospective Studies
- Surveys and Questionnaires
- Weight Gain
Epigenetic states can govern the plasticity of a genome to be adaptive to environments where many stress stimuli and insults compromise the homeostatic system with age. Although certain elastic power may autonomously reset, reprogram, rejuvenate, or reverse the organismal aging process, enforced genetic manipulations could at least reset and reprogram epigenetic states beyond phenotypic plasticity and elasticity in cells, which can be further manipulated into organisms. The question, however, remains how we can rejuvenate intrinsic resources and infrastructures in a noninvasive manner, particularly in a whole complex aging organism. Given inevitable increase of cancer with age, presumably any failure of resetting, reprogramming, or even rejuvenation could be a prominent causative factor of malignancy. Accompanied by progressive deteriorations of physiological functions in organisms with advancing age, aging-associated cancer risk may essentially arise from unforeseen complications in cellular senescence. At the cellular level, epithelial-mesenchymal plasticity (dynamic and reversible transitions between epithelial and mesenchymal phenotypic states) is enabled by underlying shifts in epigenetic regulation. Thus, the epithelial-mesenchymal transition (EMT) and its reversal (mesenchymal-epithelial transition [[[MET]]]) function as a key of cellular transdifferentiation programs. On the one hand, the EMT-MET process was initially appreciated in developmental biology, but is now attracting increasing attention in oncogenesis and senescence, because the process is involved in the malignant progression vs regression of cancer. On the other hand, senescence is often considered the antithesis of early development, but yet between these 2 phenomena, there may be common factors and governing mechanisms such as the EMT-MET program, to steer toward rejuvenation of the biological aging system, thereby precisely controlling or avoiding cancer through epigenetic interventions.
MeSH Terms
- Aging
- Animals
- Cell Transdifferentiation
- Cellular Senescence
- Epigenesis, Genetic
- Epithelial-Mesenchymal Transition
- Growth and Development
- Humans
- Neoplasms
- Transcription Factors
- Translational Medical Research
We evaluated how the intensity of physical exercise as a lifestyle habit is associated with age, body composition and handgrip strength. Total body composition was analyzed using DEXA. Exercise scores were derived from an administered questionnaire and the scoring was calculated using the Metabolic Equivalent of Task (MET). Handgrip strength was measured using a dynamometer. Age, independent of exercise intensity, was associated with declining lean mass, and handgrip strength and with increasing total body fat. A regular physical exercise regime of intensity greater than 1230 MET-min/week was associated with higher total lean mass and lean mass in the limbs, and handgrip strength and lower fat mass in the limbs. We have shown that age was associated with lower lean mass especially in the limbs and handgrip strength and higher total fat mass. Regular physical exercise as a lifestyle habit of any type and of sufficient intensity could help improve muscle strength in the limbs.
MeSH Terms
- Adipose Tissue
- Adult
- Age Factors
- Aged
- Asian Continental Ancestry Group
- Body Composition
- Body Mass Index
- Body Weight
- Exercise
- Hand Strength
- Humans
- Life Style
- Male
- Middle Aged
Keywords
- Aging men
- Asian men
- exercise
- grip strength
- lean muscle mass
Aging, even in otherwise healthy subjects, is associated with declines in muscle mass, strength, and aerobic capacity. Older individuals respond favorably to exercise, suggesting that physical inactivity plays an important role in age-related functional decline. Conversely, physical activity and improved exercise capacity are associated with lower mortality risk in hypertensive individuals. However, the effect of exercise capacity in older hypertensive individuals has not been investigated extensively. A total of 2153 men with hypertension, aged ≥70 years (mean, 75 ± 4) from the Washington, DC, and Palo Alto Veterans Affairs Medical Centers, underwent routine exercise tolerance testing. Peak workload was estimated in metabolic equivalents (METs). Fitness categories were established based on peak METs achieved, adjusted for age: very-low-fit, 2.0 to 4.0 METs (n=386); low-fit, 4.1 to 6.0 METs (n=1058); moderate-fit, 6.1 to 8.0 METs (n=495); high-fit >8.0 METs (n=214). Cox proportional hazard models were applied after adjusting for age, body mass index, race, cardiovascular disease, cardiovascular medications, and risk factors. All-cause mortality was quantified during a mean follow-up period of 9.0 ± 5.5 years. There were a total of 1039 deaths or 51.2 deaths per 1000 person-years of follow-up. Mortality risk was 11% lower (hazard ratio, 0.89; 95% confidence interval, 0.86-0.93; P<0.001) for every 1-MET increase in exercise capacity. When compared with those achieving ≤4.0 METs, mortality risk was 18% lower (hazard ratio, 0.82; 95% confidence interval, 0.70-0.95; P=0.011) for the low-fit, 36% for the moderate-fit (hazard ratio, 0.64; 95% confidence interval, 0.52-0.78; P<0.001), and 48% for the high-fit individuals (hazard ratio, 0.52; 95% confidence interval, 0.39-0.69; P<0.001). These findings suggest that exercise capacity is associated with lower mortality risk in elderly men with hypertension.
MeSH Terms
- Aged
- Aged, 80 and over
- Aging
- Blood Pressure
- Body Mass Index
- Exercise
- Exercise Test
- Exercise Tolerance
- Humans
- Hypertension
- Male
- Physical Fitness
- Risk
- Veterans
Keywords
- hypertension
- mortality
Higher physical activity (PA) levels are known to be associated with lower risk of death. Less attention, however, has been paid to directly evaluate the effect of PA on the time by which a certain fraction of the population has died. A population-based cohort of 29,362 men 45 to 79 years of age was followed from January 1998 to December 2010. A total of 4,570 men died. PA was assessed through a self-administrated questionnaire. Adjusted differences in the number of months by which 10% (10th percentile) of the cohort has died, according to levels of total PA (TPA) and different domains of PA were estimated using Laplace regression. Overall, the 10th survival percentile was 9.6 years, that is, 90% of the cohort lived longer than 9.6 years. We found a strong evidence of non-linearity between TPA and the 10th survival percentile (P-value < 0.001). Compared to men with the lowest TPA (29 metabolic equivalents (MET)-hrs/day), men with a median TPA (41 MET-hrs/day) had 30 months longer survival (95% CI: 25-35). Below the median TPA, every increment of 4 MET-hrs/day, approximately a 30 minutes brisk pace daily walk, was associated with a longer survival of 11 months (95% CI: 8-15). Above the median TPA additional activity was not significantly associated with better survival. We found that a physically active lifestyle is associated with a substantial improvement in survival time, up to 2.5 years over 13 years of follow-up.
MeSH Terms
- Aged
- Exercise
- Health Behavior
- Humans
- Life Style
- Longevity
- Male
- Metabolic Equivalent
- Middle Aged
- Mortality
- Prospective Studies
- Surveys and Questionnaires
- Walking
Physical inactivity is an important modifiable risk factor for noncommunicable disease. The degree to which physical activity affects the life expectancy of Americans is unknown. This study estimated the potential years of life gained due to leisure-time physical activity in the U.S. Data from the National Health and Nutrition Examination Survey (2007-2010); National Health Interview Study mortality linkage (1990-2006); and U.S. Life Tables (2006) were used to estimate and compare life expectancy at each age of adult life for inactive (no moderate to vigorous physical activity); somewhat-active (some moderate to vigorous activity but <500 MET minutes/week); and active (≥ 500 MET minutes/week of moderate to vigorous activity) adults. Analyses were conducted in 2012. Somewhat-active and active non-Hispanic white men had a life expectancy at age 20 years that was ~2.4 years longer than that for the inactive men; this life expectancy advantage was 1.2 years at age 80 years. Similar observations were made in non-Hispanic white women, with a higher life expectancy within the active category of 3.0 years at age 20 years and 1.6 years at age 80 years. In non-Hispanic black women, as many as 5.5 potential years of life were gained due to physical activity. Significant increases in longevity were also observed within somewhat-active and active non-Hispanic black men; however, among Hispanics the years-of-life-gained estimates were not significantly different from 0 years gained. Leisure-time physical activity is associated with increases in longevity.
MeSH Terms
- Adult
- African Americans
- Aged
- Aged, 80 and over
- Cross-Sectional Studies
- European Continental Ancestry Group
- Female
- Health Surveys
- Hispanic Americans
- Humans
- Leisure Activities
- Life Expectancy
- Male
- Middle Aged
- Motor Activity
- Nutrition Surveys
- Risk Factors
- United States
- Young Adult