Cardiac benefits of exercise training in aging spontaneously hypertensive rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Dysarthria and quality of life in neurologically healthy elderly and patients with Parkinson's disease

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Eccentric torque-producing capacity is influenced by muscle length in older healthy adults

Considering the importance of muscle strength to functional capacity in the elderly, the study investigated the effects of age on isokinetic performance and torque production as a function of muscle length. Eleven younger (24.2±2.9years) and seventeen older men (62.7±2.5years) were subjected to concentric and eccentric isokinetic knee extension/flexion at 60°.s-1 and 120°.s-1 through a functional range of motion. The older group presented lower peak torque (Nm) than the young group for both isokinetic contraction types (age effect, p<0.001). Peak torque deficits in the older group were near 30% and 29% for concentric and eccentric contraction, respectively. Concentric peak torque was lower at 120.s-1 than at 60.s-1 for both groups (angular velocity effect, p<0.001). Eccentric knee extension torque was the only exercise tested that showed an interaction effect between age and muscle length (p<0.001), which suggested different torque responses to the muscle length between groups. Compared with the young group, the eccentric knee extension torque was 22% to 56% lower in the older group, with the deficits being lower in the shortened muscle length (22-27%) and higher (33-56%) in stretched muscle length. In older men, the production of eccentric knee strength seems to be muscle length-dependent. At more stretched positions, older subjects lose the capacity to generate eccentric knee extension torque. More studies are needed to assess the mechanisms involved in eccentric strength preservation with aging and its relationship with muscle length.

Instrumental activities of daily living performance in healthy and cognitively intact seniors from a Brazilian sample and its relation to age and other socio-demographic variables

Background: Studies on functional capacity in community-dwelling older people have shown associations between declines in instrumental activities of daily living (IADL) and several factors. Among these, age has been the most consistently related to functional capacity independent of other variables. We aimed at evaluating the performance of a sample of healthy and cognitively intact Brazilian older people on activities of daily living and to analyze its relation to social-demographic variables. Methods: We conducted a secondary analysis of data collected for previous epidemiological studies with community-dwelling subjects aged 60 years or more. We selected subjects who did not have dementia or depression, and with no history of neurological diseases, heart attack, HIV, hepatitis or arthritis (n = 1,111). Functional capacity was assessed using the Brazilian version of the Older American Resources and Services Questionnaire (BOMFAQ). ADL performance was analyzed according to age, gender, education, and marital status (Pearson's chi(2), logistic regression). Results: IADL difficulties were present in our sample, especially in subjects aged 80 years or more, with lower levels of education, or widowed. The logistic regression analysis results indicated that "higher age" and "lower education" (p <= 0.001) remained significantly associated with IADL difficulty. Conclusions: Functional decline was present in older subjects even in the absence of medical conditions and cognitive impairment. Clinicians and researchers could benefit from knowing what to expect from older people regarding IADL performance in the absence of medical conditions.

Aging reduces complexity of heart rate variability assessed by conditional entropy and symbolic analysis

Increasing age is associated with a reduction in overall heart rate variability as well as changes in complexity of physiologic dynamics. The aim of this study was to verify if the alterations in autonomic modulation of heart rate caused by the aging process could be detected by Shannon entropy (SE), conditional entropy (CE) and symbolic analysis (SA). Complexity analysis was carried out in 44 healthy subjects divided into two groups: old (n = 23, 63 +/- A 3 years) and young group (n = 21, 23 +/- A 2). It was analyzed SE, CE [complexity index (CI) and normalized CI (NCI)] and SA (0V, 1V, 2LV and 2ULV patterns) during short heart period series (200 cardiac beats) derived from ECG recordings during 15 min of rest in a supine position. The sequences characterized by three heart periods with no significant variations (0V), and that with two significant unlike variations (2ULV) reflect changes in sympathetic and vagal modulation, respectively. The unpaired t test (or Mann-Whitney rank sum test when appropriate) was used in the statistical analysis. In the aging process, the distributions of patterns (SE) remain similar to young subjects. However, the regularity is significantly different; the patterns are more repetitive in the old group (a decrease of CI and NCI). The amounts of pattern types are different: 0V is increased and 2LV and 2ULV are reduced in the old group. These differences indicate marked change of autonomic regulation. The CE and SA are feasible techniques to detect alteration in autonomic control of heart rate in the old group.

Frontal assessment battery in a Brazilian sample of healthy controls: normative data

Objective: To show data on the performance of healthy subjects in the Frontal Assessment Battery (FAB), correlating with gender, age, education, and scores in the Mini-Mental State Examination (MMSE). Methods: Two hundred and seventy-five healthy individuals with mean age of 66.4 +/- 10.6 years-old were evaluated. Mean total FAB scores were established according to the educational level. Results: Mean total FAB scores according to the educational level were 10.9 +/- 2.3, for one to three years; 12.8 +/- 2.7, for four to seven years; 13.8 +/- 2.2, for eight to 11 years; and 15.3 +/- 2.3, for 12 or more years. Total FAB scores correlated significantly with education (r=0.47; p<0.0001) and MMSE scores (r=0.39; p<0.0001). No correlation emerged between FAB scores, age, and gender. Conclusion: In this group of healthy subjects, the Brazilian version of the FAB proved to be influenced by the education level, but not by age and gender.

Bioelectrical impedance with different equations versus deuterium oxide dilution method for the inference of body composition in healthy older persons

There is no consensus regarding the accuracy of bioimpedance for the determination of body composition in older persons. This study aimed to compare the assessment of lean body mass of healthy older volunteers obtained by the deuterium dilution method (reference) with those obtained by two frequently used bioelectrical impedance formulas and one formula specifically developed for a Latin-American population. A cross-sectional study. Twenty one volunteers were studied, 12 women, with mean age 72 +/- 6.7 years. Urban community, Ribeiro Preto, Brazil. Fat free mass was determined, simultaneously, by the deuterium dilution method and bioelectrical impedance; results were compared. In bioelectrical impedance, body composition was calculated by the formulas of Deuremberg, Lukaski and Bolonchuck and Valencia et al. Lean body mass of the studied volunteers, as determined by bioelectrical impedance was 37.8 +/- 9.2 kg by the application of the Lukaski e Bolonchuk formula, 37.4 +/- 9.3 kg (Deuremberg) and 43.2 +/- 8.9 kg (Valencia et. al.). The results were significantly correlated to those obtained by the deuterium dilution method (41.6 +/- 9.3 Kg), with r=0.963, 0.932 and 0.971, respectively. Lean body mass obtained by the Valencia formula was the most accurate. In this study, lean body mass of older persons obtained by the bioelectrical impedance method showed good correlation with the values obtained by the deuterium dilution method. The formula of Valencia et al., developed for a Latin-American population, showed the best accuracy.

Molecular characterization of the human gut microbiota: the effect of aging

Age-related physiological changes in the gastrointestinal tract, as well as modification in lifestyle, nutritional behaviour, and functionality of the host immune system, inevitably affect the gut microbiota. The study presented here is focused on the application and comparison of two different microarray approaches for the characterization of the human gut microbiota, the HITChip and the HTF-Microb.Array, with particular attention to the effects of the aging process on the composition of this ecosystem. By using the Human Intestinal Tract Chip (HITChip), recently developed at the Wageningen University, The Netherland, we explored the age-related changes of gut microbiota during the whole adult lifespan, from young adults, through elderly to centenarians. We observed that the microbial composition and diversity of the gut ecosystem of young adults and seventy-years old people is highly similar but differs significantly from that of the centenarians. After 100 years of symbiotic association with the human host, the microbiota is characterized by a rearrangement in the Firmicutes population and an enrichment of facultative anaerobes. The presence of such a compromised microbiota in the centenarians is associated with an increased inflammation status, also known as inflamm-aging, as determined by a range of peripheral blood inflammatory markers. In parallel, we overtook the development of our own phylogenetic microarray with a lower number of targets, aiming the description of the human gut microbiota structure at high taxonomic level. The resulting chip was called High Taxonomic level Fingerprinting Microbiota Array (HTF-Microb.Array), and was based on the Ligase Detection Reaction (LDR) technology, which allowed us to develop a fast and sensitive tool for the fingerprint of the human gut microbiota in terms of presence/absence of the principal groups. The validation on artificial DNA mixes, as well as the pilot study involving eight healthy young adults, demonstrated that the HTF-Microb.Array can be used to successfully characterize the human gut microbiota, allowing us to obtain results which are in approximate accordance with the most recent characterizations. Conversely, the evaluation of the relative abundance of the target groups on the bases of the relative fluorescence intensity probes response still has some hindrances, as demonstrated by comparing the HTF.Microb.Array and HITChip high taxonomic level fingerprints of the same centenarians.

Glycomics as an innovative technology to identify biomarkers of aging

Introduction. Glycomic analysis allows investigating on the global glycome within body fluids (as serum/plasma), this could eventually lead to identify new types of disease biomarkers, or as in this study, biomarkers of human aging studying specific aging models. Recent studies demonstrated that the plasma N-glycome is modified during human aging, suggesting that measurements of log-ratio of two serum/plasma N-glycans (NGA2F and NA2F), named GlycoAge test could provide a non-invasive biomarker of aging. Down syndrome (DS) is a genetic disorder in which multiple major aspects of senescent phenotype occur much earlier than in healthy age-matched subjects and has been often defined as an accelerated aging syndrome. The aim of this study was to compare plasma N-glycome of patients affected by DS with age- and sex matched non-affected controls, represented by their siblings (DSS), in order to assess if DS is characterized by a specific N-glycomic pattern. Therefore, in order to investigate if N-glycans changes that occur in DS were able to reveal an accelerated aging in DS patients, we enrolled the mothers (DSM) of the DS and DSS, representing the non-affected control group with a different chronological age respect to DS. We applied two different N-glycomics approaches on the same samples: first, in order to study the complete plasma N-glycome we applied a new high-sensitive protocol based on a MALDI-TOF-MS approach, second, we used DSA-FACE technology. Results: MALDI-TOF/MS analysis detected a specific N-glycomics signature for DS, characterized by an increase of fucosylated and bisecting species. Moreover, in DS the abundance of agalactosylated (as NA2F) species was similar or higher than their mothers. The measurement of GlycoAge test with DSA-FACE, validated also by MALDI-TOF, demonstrated a strongly association with age, moreover in DS, it’s value was similar to their mothers, and significantly higher than their age- and sex matched not-affected siblings

Mitochondrial DNA rearrangements during human aging: a study on liver, muscle and adipose tissue

Aging is characterized by a chronic, low-grade inflammatory state called “inflammaging”. Mitochondria are the main source of reactive oxygen species (ROS), which trigger the production of pro-inflammatory molecules. We are interested in studying the age-related modifications of the mitochondrial DNA (mtDNA), which can be affected by the lifelong exposure to ROS and are responsible of mitochondrial dysfunction. Moreover, increasing evidences show that telomere shortening, naturally occurring with aging, is involved in mtDNA damage processes and thus in the pathogenesis of age-related disorders. Thus the primary aim of this thesis was the analysis of mtDNA copy number, deletion level and integrity in different-age human biopsies from liver, vastus lateralis skeletal muscle of healthy subjects and patients with limited mobility of lower limbs (LMLL), as well as adipose tissue. The telomere length and the expression of nuclear genes related to mitobiogenesis, fusion and fission, mitophagy, mitochondrial protein quality control system, hypoxia, production and protection from ROS were also evaluated. In liver the decrease in mtDNA integrity with age is accompanied with an increase in mtDNA copy number, suggesting the existence of a “compensatory mechanism” able to maintain the functionality of this organ. Different is the case of vastus lateralis muscle, where any “compensatory pathway” is activated and mtDNA integrity and copy number decrease with age, both in healthy subjects and in patients. Interestingly, mtDNA rearrangements do not incur in adipose tissue with advancing age. Finally, in all tissues a marked gender difference appears, suggesting that aging and also gender diversely affect mtDNA rearrangements and telomere length in the three human tissues considered, likely depending on their different metabolic needs and inflammatory status.

Recognition of familiar and unfamiliar music in normal aging and Alzheimer's disease

We tested normal young and elderly adults and elderly Alzheimer’s disease (AD) patients on recognition memory for tunes. In Experiment 1, AD patients and age-matched controls received a study list and an old/new recognition test of highly familiar, traditional tunes, followed by a study list and test of novel tunes. The controls performed better than did the AD patients. The controls showed the “mirror effect” of increased hits and reduced false alarms for traditional versus novel tunes, whereas the patients false-alarmed as often to traditional tunes as to novel tunes. Experiment 2 compared young adults and healthy elderly persons using a similar design. Performance was lower in the elderly group, but both younger and older subjects showed the mirror effect. Experiment 3 produced confusion between preexperimental familiarity and intraexperimental familiarity by mixing traditional and novel tunes in the study lists and tests. Here, the subjects in both age groups resembled the patients of Experiment 1 in failing to show the mirror effect. Older subjects again performed more poorly, and they differed qualitatively from younger subjects in setting stricter criteria for more nameable tunes. Distinguishing different sources of global familiarity is a factor in tune recognition, and the data suggest that this type of source monitoring is impaired in AD and involves different strategies in younger and older adults.

Apparent diffusion coefficient in the aging mouse brain: a magnetic resonance imaging study

Novel magnetic resonance imaging sequences have and still continue to play an increasing role in neuroimaging and neuroscience. Among these techniques, diffusion-weighted imaging (DWI) has revolutionized the diagnosis and management of diseases such as stroke, neoplastic disease and inflammation. However, the effects of aging on diffusion are yet to be determined. To establish reference values for future experimental mouse studies we tested the hypothesis that absolute apparent diffusion coefficients (ADC) of the normal brain change with age. A total of 41 healthy mice were examined by T2-weighted imaging and DWI. For each animal ADC frequency histograms (i) of the whole brain were calculated on a voxel-by-voxel basis and region-of-interest (ROI) measurements (ii) performed and related to the animals' age. The mean entire brain ADC of mice <3 months was 0.715(+/-0.016) x 10(-3) mm2/s, no significant difference to mice aged 4 to 5 months (0.736(+/-0.040) x 10(-3) mm2/s) or animals older than 9 months 0.736(+/-0.020) x 10(-3) mm2/s. Mean whole brain ADCs showed a trend towards lower values with aging but both methods (i + ii) did not reveal a significant correlation with age. ROI measurements in predefined areas: 0.723(+/-0.057) x 10(-3) mm2/s in the parietal lobe, 0.659(+/-0.037) x 10(-3) mm2/s in the striatum and 0.679(+/-0.056) x 10(-3) mm2/s in the temporal lobe. With advancing age, we observed minimal diffusion changes in the whole mouse brain as well as in three ROIs by determination of ADCs. According to our data ADCs remain nearly constant during the aging process of the brain with a small but statistically non-significant trend towards a decreased diffusion in older animals.

[Active and healthy living in old age--results from a representative survey of community-dwelling senior citizens in Hamburg]

BACKGROUND: The majority of community-dwelling people 60 years and older are independent and live actively. However, there is little information about elderly persons' views on aging, health and health promotion. METHODS: Therefore, an anonymous, written questionnaire survey was performed in a representative sample of inhabitants from a section of the city of Hamburg, 60 years and older; 5 year intervals, 14 subsamples according to 7 age groups of females and males. RESULTS: Questionnaires from 950 participants (29% response) could be evaluated: mean age 71.5 years, 58% women, 34% living alone, 5% with professional healthcare needs as indicated by status according to German nursing care insurance. Senior citizens' positive attitudes towards aging and health were predominant: 69% of respondents felt young, 85% worried about loss of autonomy in old age. CONCLUSIONS: The results provide evidence indicating potential for improving health-promoting lifestyles in parts of the older population by evaluating and strengthening older persons' competencies and by considering their concerns seriously. These results provide valuable information for future plans in the public-health sector in the city of Hamburg where particular health-promoting actions for elderly persons will be considered.

β2-microglobulin is a systemic pro-aging factor that impairs cognitive function and neurogenesis

Aging drives cognitive and regenerative impairments in the adult brain, increasing susceptibility to neurodegenerative disorders in healthy individuals. Experiments using heterochronic parabiosis, in which the circulatory systems of young and old animals are joined, indicate that circulating pro-aging factors in old blood drive aging phenotypes in the brain. Here we identify β2-microglobulin (B2M), a component of major histocompatibility complex class 1 (MHC I) molecules, as a circulating factor that negatively regulates cognitive and regenerative function in the adult hippocampus in an age-dependent manner. B2M is elevated in the blood of aging humans and mice, and it is increased within the hippocampus of aged mice and young heterochronic parabionts. Exogenous B2M injected systemically, or locally in the hippocampus, impairs hippocampal-dependent cognitive function and neurogenesis in young mice. The negative effects of B2M and heterochronic parabiosis are, in part, mitigated in the hippocampus of young transporter associated with antigen processing 1 (Tap1)-deficient mice with reduced cell surface expression of MHC I. The absence of endogenous B2M expression abrogates age-related cognitive decline and enhances neurogenesis in aged mice. Our data indicate that systemic B2M accumulation in aging blood promotes age-related cognitive dysfunction and impairs neurogenesis, in part via MHC I, suggesting that B2M may be targeted therapeutically in old age.

Association between body composition, circulating irisin and telomere length in healthy individuals and individuals with Type 2 diabetes

Aims: Obesity and Type 2 diabetes are associated with accelerated ageing. The underlying mechanisms behind this, however, are poorly understood. In this study, we investigated the association between circulating irisin - a novel my okine involved in energy regulation - and telomere length (TL) (a marker of aging) in healthy individuals and individuals with Type 2 diabetes. Methods: Eighty-two healthy people and 67 subjects with Type 2 diabetes were recruited to this cross-sectional study. Anthropometric measurements including body composition measured by biompedance were recorded. Plasma irisin was measured by ELISA on a fasted blood sample. Relative TL was determined using real-time PCR. Associations between anthropometric measures and irisin and TL were explored using Pearson’s bivariate correlations. Multiple regression was used to explore all the significant predictors of TL using backward elimination. Results: In healthy individuals chronological age was a strong negative predictor of TL (=0.552, p < 0.001). Multiple regression analysis using backward elimination (excluding age) revealed the greater relative TL could be predicted by greater total muscle mass(b = 0.046, p = 0.001), less visceral fat (b = =0.183, p < 0.001)and higher plasma irisin levels (b = 0.01, p = 0.027). There were no significant associations between chronological age, plasmairisin, anthropometric measures and TL in patients with Type 2diabetes (p > 0.1). Conclusion: These data support the view that body composition and plasma irisin may have a role in modulation of energy balance and the aging process in healthy individuals. This relationship is altered in individuals with Type 2 diabetes.