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Age (Dordrecht, Netherlands) Feb 2016Aging leads to several anatomical and functional deficits in circadian timing system. In previous works, we observed morphological alterations with age in hypothalamic...
Aging leads to several anatomical and functional deficits in circadian timing system. In previous works, we observed morphological alterations with age in hypothalamic suprachiasmatic nuclei, one central component of this system. However, there are few data regarding aging effects on other central components of this system, such as thalamic intergeniculate leaflet (IGL). In this context, we studied possible age-related alterations in neurochemical components and retinal projections of rat IGL. For this goal, young (3 months), adult (13 months), and aged (23 months) Wistar rats were submitted to an intraocular injection of neural tracer, cholera toxin subunit b (CTb), 5 days before a tissue fixation process by paraformaldehyde perfusion. Optical density measurements and cell count were performed at digital pictures of brain tissue slices processed by immunostaining for glutamic acid decarboxylase (GAD), enkephalin (ENK), neuropeptide Y (NPY) and CTb, characteristic markers of IGL and its retinal terminals. We found a significant age-related loss in NPY immunoreactive neurons, but not in immunoreactivity to GAD and ENK. We also found a decline of retinal projections to IGL with age. We conclude aging impairs both a photic environmental clue afferent to IGL and a neurochemical expression which has an important modulatory circadian function, providing strong anatomical correlates to functional deficits of the aged biological clock.
Topics: Aging; Animals; Circadian Rhythm; Hypothalamus; Immunohistochemistry; Male; Neurons; Neuropeptide Y; Rats; Rats, Wistar; Retina; Suprachiasmatic Nucleus
PubMed: 26718202
DOI: 10.1007/s11357-015-9867-9 -
Age (Dordrecht, Netherlands) Jun 2016Age-related changes in motor unit activation properties remain unclear for locomotor muscles such as quadriceps muscles, although these muscles are preferentially...
Age-related changes in motor unit activation properties remain unclear for locomotor muscles such as quadriceps muscles, although these muscles are preferentially atrophied with aging and play important roles in daily living movements. The present study investigated and compared detailed motor unit firing characteristics for the vastus lateralis muscle during isometric contraction at low to moderate force levels in the elderly and young. Fourteen healthy elderly men and 15 healthy young men performed isometric ramp-up contraction to 70 % of the maximal voluntary contractions (MVC) during knee extension. Multichannel surface electromyograms were recorded from the vastus lateralis muscle using a two-dimensional grid of 64 electrodes and decomposed with the convolution kernel compensation technique to extract individual motor units. Motor unit firing rates in the young were significantly higher (~+29.7 %) than in the elderly (p < 0.05). There were significant differences in firing rates among motor units with different recruitment thresholds at each force level in the young (p < 0.05) but not in the elderly (p > 0.05). Firing rates at 60 % of the MVC force level for the motor units recruited at <20 % of MVC were significantly correlated with MVC force in the elderly (r = 0.885, p < 0.0001) but not in the young (r = 0.127, p > 0.05). These results suggest that the motor unit firing rate in the vastus lateralis muscle is affected by aging and muscle strength in the elderly and/or age-related strength loss is related to motor unit firing/recruitment properties.
Topics: Adult; Aged; Aged, 80 and over; Aging; Electromyography; Humans; Isometric Contraction; Male; Middle Aged; Muscle Fatigue; Muscle Strength; Quadriceps Muscle; Recruitment, Neurophysiological
PubMed: 27084115
DOI: 10.1007/s11357-016-9915-0 -
Age (Dordrecht, Netherlands) Dec 2011A major problem of ageing is progressive impairment of neuronal function and ultimately cell death. Since sex steroids are neuroprotective, their decrease with age may...
A major problem of ageing is progressive impairment of neuronal function and ultimately cell death. Since sex steroids are neuroprotective, their decrease with age may underlie age-related neuronal degeneration. To test this, we examined Purkinje cell numbers, plasma sex steroids and cerebellar neurosteroid concentrations during normal ageing (wild-type mice, WT), in our model of precocious ageing (Rora(+/sg), heterozygous staggerer mice in which expression of the neuroprotective factor RORα is disrupted) and after long-term hormone insufficiency (WT post-gonadectomy). During normal ageing (WT), circulating sex steroids declined prior to or in parallel with Purkinje cell loss, which began at 18 months of age. Although Purkinje cell death was advanced in WT long-term steroid deficiency, this premature neuronal loss did not begin until 9 months, indicating that vulnerability to sex steroid deficiency is a phenomenon of ageing Purkinje neurons. In precocious ageing (Rora(+/sg)), circulating sex steroids decreased prematurely, in conjunction with marked Purkinje cell death from 9 months. Although Rora(+/sg) Purkinje cells are vulnerable through their RORα haplo-insufficiency, it is only as they age (after 9 months) that sex steroid failure becomes critical. Finally, cerebellar neurosteroids did not decrease with age in either genotype or gender; but were profoundly reduced by 3 months in male Rora(+/sg) cerebella, which may contribute to the fragility of their Purkinje neurons. These data suggest that ageing Purkinje cells are maintained by circulating sex steroids, rather than local neurosteroids, and that in Rora(+/sg) their age-related death is advanced by premature sex steroid loss induced by RORα haplo-insufficiency.
Topics: Aging; Animals; Castration; Cell Count; Cell Death; Cell Survival; Cerebellum; Estradiol; Female; Gonadal Steroid Hormones; Hormone Replacement Therapy; Male; Mice; Mice, Mutant Strains; Mice, Neurologic Mutants; Nuclear Receptor Subfamily 1, Group F, Member 1; Progesterone; Purkinje Cells; Testosterone
PubMed: 21222044
DOI: 10.1007/s11357-010-9203-3 -
Age (Dordrecht, Netherlands) Apr 2014Declines in muscle size and strength are commonly reported as a consequence of aging; however, few studies have investigated the influence of aging on the rate of muscle... (Comparative Study)
Comparative Study
Declines in muscle size and strength are commonly reported as a consequence of aging; however, few studies have investigated the influence of aging on the rate of muscle activation and rapid force characteristics across the lifespan. This study aims to investigate the effects of aging on the rate of muscle activation and rapid force characteristics of the plantar flexors. Plantar flexion peak force (PF), absolute (peak, 50, and 100-200 ms), and relative (10 %, 30 %, and 50 %) rate of force development (RFD), the rapid to maximal force ratio (RFD/PF), and the rate of electromyography rise (RER) were examined during an isometric maximal voluntary contraction (MVC) in young (age = 22 ± 2 years), middle-aged (43 ± 2 years), and old (69 ± 5 years) men. The old men exhibited lower PF (30.7 % and 27.6 % lower, respectively) and absolute (24.4-55.1 %) and relative (16.4-28.9 %) RFD values compared to the young and middle-aged men (P ≤ 0.03). RER values were similar between the young and old men (P ≥ 0.30); however, RER values were greater for the middle-aged men when compared to the young and old men for the soleus (P < 0.01) and the old men for the medial gastrocnemius (P ≤ 0.02). Likewise, RFD/PF ratios were similar between young and old men (P ≥ 0.26); however, these ratios were greater for the middle-aged men at early (P ≤ 0.03), but not later (P ≥ 0.10), time intervals. The lower PF and absolute and relative RFD values for the old men may contribute to the increased functional limitations often observed in older adults. Interestingly, higher rates of muscle activation and greater early RFD/PF ratios in middle-aged men may be a reflection of physiological alterations in the neuromuscular system occurring in the fifth decade.
Topics: Adult; Aged; Aging; Electromyography; Follow-Up Studies; Healthy Volunteers; Humans; Isometric Contraction; Male; Middle Aged; Muscle Strength Dynamometer; Muscle, Skeletal; Young Adult
PubMed: 24338233
DOI: 10.1007/s11357-013-9605-0 -
Age (Dordrecht, Netherlands) Feb 2014To clarify age-related histological and Zn content changes in nonhyperplastic adult prostate glands, a quantitative morphometric and energy-dispersive X-ray fluorescence...
To clarify age-related histological and Zn content changes in nonhyperplastic adult prostate glands, a quantitative morphometric and energy-dispersive X-ray fluorescence analyses were performed. The prostates were obtained from autopsies of 63 subjects aged 21-70 years who died mainly from trauma. It was found that histologically normal prostate tissue undergoes substantial changes throughout aging. These changes are reflected in an increase of the percent volume of the glandular lumen for the third to fifth decades, reaching a maximum for the decade 41-50 years. Over the same period, the percent volume of the stroma remains steady, but the percent volume of epithelium decreases, approximately, linearly with age. The percent volume of glandular lumen (reflects the volume of prostatic fluid) in the prostate gland of men aged 41 to 50 years is 1.5-fold higher than that in men aged 21 to 30 years, but the epithelium/lumen (prostatic fluid) ratio is approximately twofold lower. This suggests that accumulation of the prostatic fluid develops from 30 to 50 years of age. This accumulation of the prostatic fluid results in an increase of the Zn mass fraction in the prostate. In turn, when the intraprostatic Zn level exceeds a certain level by the end of the fifth decade, it begins to work as a trigger for different factors, all of which increase the proliferation of stromal cells. Deductions from these results allow possible partial explanations of both relevant prostatic aging mechanisms and the effects of dietary interventions using supplementary Zn.
Topics: Adult; Age Factors; Aged; Autopsy; Humans; Male; Middle Aged; Polarography; Prostate; Spectrometry, X-Ray Emission; Spectrophotometry, Atomic; Zinc
PubMed: 23852618
DOI: 10.1007/s11357-013-9561-8 -
Age (Dordrecht, Netherlands) 2014The Fischer 344/NNiaHSD × Brown Norway/BiNia F1 (F344xBN) rat model exhibits an increased life span and fewer age-associated pathologies compared to commonly used...
The Fischer 344/NNiaHSD × Brown Norway/BiNia F1 (F344xBN) rat model exhibits an increased life span and fewer age-associated pathologies compared to commonly used Fischer 344 (F344). How aging may affect cardiac structure and function in these animals, has to our knowledge, not been investigated. Echocardiography was performed on female F344xBN rats at 6, 26, and 30 months of age using a Phillips 5500 Echocardiography system. Before sacrifice, electrocardiograms were measured in the female F344xBN in order to determine heart rhythm interval changes. Aging was associated with an increase in heart to body weight ratio, cardiomyocyte cross-sectional area, posterior wall thickening, and left ventricle chamber dilatation. Aging was associated with slight evidence of diastolic dysfunction. Alterations in heart rhythm intervals were associated with alterations in the spatial distribution of connexin 43. The incidence of arrhythmias was not different with age; however, valvular dysfunction was increased. These data suggest that aging in the female F344xBN rat heart is associated with changes in cardiac structure as well as function. Further investigation regarding other parameters of cardiac biochemistry and function is needed to better understand the normal compensated cardiovascular aging process in the female F344xBN.
Topics: Aging; Animals; Arrhythmias, Cardiac; Body Weight; Disease Models, Animal; Echocardiography; Female; Heart Rate; Myocardium; Rats; Rats, Inbred BN; Rats, Inbred F344; Ventricular Function
PubMed: 25062714
DOI: 10.1007/s11357-014-9684-6 -
Age (Dordrecht, Netherlands) Jun 2011Immunosenescence is characterized by phenotypic and functional changes of effector memory T cells. In spite of the well-described senescent defects of these experienced...
Immunosenescence is characterized by phenotypic and functional changes of effector memory T cells. In spite of the well-described senescent defects of these experienced T cells, immune responses to new pathogens are also deeply affected in elderly humans, suggesting that naive T cells could also show age-related defects. It has been reported in both, animal models and humans, alterations of the naive T cell turnover associated to advanced age or low thymic function. However, as far as we know, homeostatic mechanisms involved in the deregulation of naive T cell peripheral dynamics and their consequences are still not well understood. Thus, the aim of our study was to analyze homeostatic parameters of peripheral naive T cells and their relationship with thymic function in young and elderly humans. Our results show that lower naive T cell numbers were associated with a lower thymic function and higher activation and proliferating naive T cell levels. We then analyzed sjTREC numbers and relative telomere length from sorted naive T cells. Our results show that the aberrant activation and proliferation status was related to lower sjTREC numbers (a peripheral proliferation marker) and both, higher CD57 expression levels and shortened telomeres (replicative senescence-related markers). Elderly individuals show a greater contraction of the CD8 naive T cell numbers and all homeostatic alterations were more severe in this compartment. In addition, we found that low functional thymus show a CD4-biased thymocyte production. Taken together, our results suggest a homeostatic deregulation, affecting mostly the naive CD8 T cell subset, leading to the accumulation of age-associated defects in, otherwise, phenotypically naive T cells.
Topics: Adult; Aged; Aging; CD4 Lymphocyte Count; CD8-Positive T-Lymphocytes; Female; Gene Rearrangement, T-Lymphocyte; Homeostasis; Humans; Immunoglobulin G; Immunologic Memory; Interleukin-7; Lymphocyte Subsets; Male; Middle Aged; T-Lymphocytes; Telomere
PubMed: 20700658
DOI: 10.1007/s11357-010-9170-8 -
Age (Dordrecht, Netherlands) Oct 2013Aging markedly affects mitochondrial biogenesis and functions particularly in tissues highly dependent on the organelle's bioenergetics capability such as the brain's...
Aging markedly affects mitochondrial biogenesis and functions particularly in tissues highly dependent on the organelle's bioenergetics capability such as the brain's frontal cortex. Calorie restriction (CR) diet is, so far, the only intervention able to delay or prevent the onset of several age-related alterations in different organisms. We determined the contents of mitochondrial transcription factor A (TFAM), mitochondrial DNA (mtDNA), and the 4.8-kb mtDNA deletion in the frontal cortex from young (6-month-old) and aged (26-month-old), ad libitum-fed (AL) and calorie-restricted (CR), rats. We found a 70 % increase in TFAM amount, a 25 % loss in mtDNA content, and a 35 % increase in the 4.8-kb deletion content in the aged AL animals with respect to the young rats. TFAM-specific binding to six mtDNA regions was analyzed by mtDNA immunoprecipitation and semiquantitative polymerase chain reaction (PCR), showing a marked age-related decrease. Quantitative real-time PCR at two subregions involved in mtDNA replication demonstrated, in aged AL rats, a remarkable decrease (60-70 %) of TFAM-bound mtDNA. The decreased TFAM binding is a novel finding that may explain the mtDNA loss in spite of the compensatory TFAM increased amount. In aged CR rats, TFAM amount increased and mtDNA content decreased with respect to young rats' values, but the extent of the changes was smaller than in aged AL rats. Attenuation of the age-related effects due to the diet in the CR animals was further evidenced by the unchanged content of the 4.8-kb deletion with respect to that of young animals and by the partial prevention of the age-related decrease in TFAM binding to mtDNA.
Topics: Aging; Animals; Blotting, Western; Caloric Restriction; Cerebral Cortex; DNA Damage; DNA Replication; DNA, Mitochondrial; Disease Models, Animal; Frontal Lobe; Gene Deletion; Rats; Real-Time Polymerase Chain Reaction; Transcription Factors
PubMed: 22945739
DOI: 10.1007/s11357-012-9465-z -
Age (Dordrecht, Netherlands) 2015Age-related effects are often included as covariates in the analytical model for genome-wide association analysis of quantitative traits reflecting human health....
Age-related effects are often included as covariates in the analytical model for genome-wide association analysis of quantitative traits reflecting human health. Nevertheless, previous studies have hardly examined the effects of age on the proportion of variation explained by single nucleotide polymorphisms (PVSNP) in these traits. In this study, the PVSNP estimates of body mass index (BMI), waist-to-hip ratio, pulse pressure, high-density lipoprotein cholesterol level, triglyceride level (TG), low-density lipoprotein cholesterol level, and glucose level were obtained from Korean consortium metadata partitioned by gender or by age. Restricted maximum likelihood estimates of the PVSNP were obtained in a mixed model framework. Previous studies using pedigree data suggested possible differential heritability of certain traits with regard to gender, which we observed in our current study (BMI and TG; P < 0.05). However, the PVSNP analysis based on age revealed that, with respect to every trait tested, individuals aged 40 to 49 exhibited significantly lower PVSNP estimates than individuals aged 50 to 59 or 60 to 69 (P < 0.05). The consistent heterogeneous PVSNP with respect to age may be due to degenerated genetic functions in individuals between the ages of 50 and 69. Our results suggest the genetic mechanism of age- and gender-dependent PVSNP of quantitative traits related to human health should be further examined.
Topics: Adult; Age Factors; Aged; Female; Genetic Variation; Health Status; Humans; Male; Middle Aged; Polymorphism, Single Nucleotide; Quantitative Trait, Heritable; Sex Factors
PubMed: 25701395
DOI: 10.1007/s11357-015-9756-2 -
Age (Dordrecht, Netherlands) Dec 2012Older adults require more time to reweight sensory information for maintaining balance that could potentially lead to increased incidence of falling in rapidly changing...
Older adults require more time to reweight sensory information for maintaining balance that could potentially lead to increased incidence of falling in rapidly changing or cognitively demanding environments. In this study, we manipulated the visual surround information during a collision avoidance task in order to investigate how young and elderly adults engage in sensory reweighting under conditions of visual anticipation. Sixteen healthy elderly (age: 71.5 ± 4.9 years; height: 159.3 ± 6.6 cm; mass: 73.3 ± 3.3 kg) and 20 young (age: 22.8 ± 3.3 years; height: 174.4 ± 10.7 cm; mass: 70.1 ± 13.9 kg) participants stood for 240 s on a force platform under two experimental conditions: quiet standing and standing while anticipating randomly approaching virtual objects to be avoided. During both tasks, the visual surround changed every 60 s from a stationary virtual scene (room) to either a moving room or darkness and then back to a stationary scene to evoke sensory reweighting processes. In quiet standing, elderly showed greater sway variability and were more severely affected by the removal or degradation of visual surround information when compared to young participants. During visual anticipation, sway variability was not different between the age groups. In addition, both young and elderly participants were similarly affected by the degradation or removal of the visual surround. These findings suggest that sensory reweighting in a dynamic virtual environment that evokes visual anticipation interacts with postural state anxiety regardless of age. Elderly show less efficient sensory reweighting in quiet standing due to greater visual field dependence possibly associated with fear of falling.
Topics: Accidental Falls; Adult; Aged; Aging; Anticipation, Psychological; Avoidance Learning; Fear; Female; Humans; Kinesthesis; Male; Postural Balance; User-Computer Interface; Visual Perception; Young Adult
PubMed: 21894445
DOI: 10.1007/s11357-011-9310-9