Cholinergic receptors in human hippocampus-- regional distribution and variance with age

The anterio-posterior distribution of cholinergic receptor binding sites in human hippocampus (five parts) as well as the effect of age (age range 3 days - 85 years) on receptor properties has been studied. Muscarinic binding sites was measured using labelled quinuclidinyl benzilate (³H-QNB) as ligand and labelled tubocurarine (³H-TC) was used for measurement of nicotine-like binding sites.The highest number of ³H-QNB binding sites in human hippocampus was measured at 3 days and 3 weeks of age and the lowest at 82 years of age. The proportion of high and low affinity muscarinic binding sites respectively was about the same at all ages investigated.A decrease in ³H-QNB binding sites with age was found in the anterior parts of the hippocampus (age range 55–84 years). When individual data for number of ³H-TC binding sites were plotted against corresponding number of ³H-QNB binding sites a strong correlation was observed in most of the different regions of the hippocampus.     

THE EFFECTS OF AGE AND ALCOHOL ON (Na++ K+)-ATPASE ACTIVITY OF WHOLE HOMOGENATE AND SYNAPTOSOMES PREPARED FROM MOUSE AND HUMAN BRAIN

Whole homogenates of mouse brain and nerve-ending fractions of mouse and human brain were obtained at various age levels representative of maturity and old age. The mice were 3, 8 and 26–29 months old and the humans ranged in age from 19 to 84 y. Measurements of (Na⁺+ K⁺)-ATPase in whole brain homogenate of mouse did not reveal any significant differences in relation to age. However, the ability of ethanol at various concentrations to inhibit membrane-bound synaptosomal (Na⁺+ K⁺)-ATPase was significantly greater in older mice and humans. The data are interpreted as indicating a change in the property of synaptic membranes as a consequence of advancing age.     

Antidepressant‐like effects and basal immobility depend on age and serotonin transporter genotype

Monoamine uptake inhibitors are common treatments for depression; however, the therapeutic efficacy of these drugs varies widely. Two factors that are commonly linked to clinical outcome are age and serotonin transporter (SERT) genotype. Mouse models provide powerful tools to study consequences of age and genotype on antidepressant‐like efficacy; however, to date, systematic studies of this nature are lacking. Here, we used the tail suspension test (TST), a preclinical assay for antidepressant efficacy, to gain insight into age and SERT genotype dependency of immobility time in the TST under control conditions (saline injection) and in response to the tricyclic antidepressant, desipramine (DMI). Immobility after saline injection in juvenile, adolescent, adult, mature adult and middle‐aged mice (postnatal days 21, 28, 90, 210 and 300, respectively) significantly increased with age; however, the rate of increase was slower for SERT null (?/?) mice than for wild‐type (+/+) or heterozygote (+/?) mice. Desipramine reduced immobility across ages and SERT genotypes. Middle‐aged, but not adult, SERT^?/? mice were significantly more sensitive to DMI than age‐matched SERT^+/+ or SERT^+/? mice. Desipramine was less potent in middle‐aged SERT^+/+ and SERT^+/? mice than in adult SERT^+/+ or SERT^+/? mice. Regardless of age, DMI's maximal effects were greater in SERT^?/? mice than in SERT^+/+ or SERT^+/? mice. These results show that immobility time in the TST varies as a function of age and SERT genotype, underscoring the utility of the TST as a potential model to examine age‐ and SERT genotype‐dependent influences on antidepressant response.     

Circulating levels of monocyte chemoattractant protein‐1 as a potential measure of biological age in mice and frailty in humans

A serum biomarker of biological versus chronological age would have significant impact on clinical care. It could be used to identify individuals at risk of early‐onset frailty or the multimorbidities associated with old age. It may also serve as a surrogate endpoint in clinical trials targeting mechanisms of aging. Here, we identified MCP‐1/CCL2, a chemokine responsible for recruiting monocytes, as a potential biomarker of biological age. Circulating monocyte chemoattractant protein‐1 (MCP‐1) levels increased in an age‐dependent manner in wild‐type (WT) mice. That age‐dependent increase was accelerated in Ercc1^?/Δ and Bubr1^H/H mouse models of progeria. Genetic and pharmacologic interventions that slow aging of Ercc1^?/Δ and WT mice lowered serum MCP‐1 levels significantly. Finally, in elderly humans with aortic stenosis, MCP‐1 levels were significantly higher in frail individuals compared to nonfrail. These data support the conclusion that MCP‐1 can be used as a measure of mammalian biological age that is responsive to interventions that extend healthy aging.     

BMI Independently Predicts Younger Age at Hip and Knee Replacement

Obesity has been identified as a risk factor for the development of hip and knee osteoarthritis (OA) and may play a role in exacerbating existing disease. Therefore, we hypothesized that obese patients would present for hip and knee replacement surgery at a younger age than nonobese patients. From our registry, we performed a cross‐sectional study of 841 hip and 804 knee replacement patients. Patients were categorized by BMI ≤25 kg/m², 25.1–29.9 kg/m², 30–34.9 kg/m², and ≥35 kg/m². Linear regression modeling was used to examine the relationship between BMI and age at surgery. Hip and knee replacement patients' mean age at surgery was 7.1 and 7.9 years younger, respectively, if their BMI was ≥35 kg/m² when compared to patients with a BMI ≤25 kg/m² (P = 0.002). BMI was a significant independent (of gender, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, surgeon, and comorbidity) predictor of age at knee replacement (P < 0.05). WOMAC scores were significantly worse preoperatively in patients with a BMI ≥35 kg/m² compared to those with a BMI ≤25 kg/m² (P < 0.05). Our study indicates that obese patients, especially those with a BMI ≥35 kg/m², presented for and underwent joint replacement surgery at a younger age as compared to nonobese patients.     

Effects of brain‐derived neurotrophic factor on dopaminergic function and motor behavior during aging

Brain‐derived neurotrophic factor (BDNF) is critical in synaptic plasticity and in the survival and function of midbrain dopamine neurons. In this study, we assessed the effects of a partial genetic deletion of BDNF on motor function and dopamine (DA) neurotransmitter measures by comparing Bdnf^+/? with wildtype mice (WT) at different ages. Bdnf^+/? and WT mice had similar body weights until 12 months of age; however, at 21 months, Bdnf^+/? mice were significantly heavier than WT mice. Horizontal and vertical motor activity was reduced for Bdnf^+/? compared to WT mice, but was not influenced by age. Performance on an accelerating rotarod declined with age for both genotypes and was exacerbated for Bdnf^+/? mice. Body weight did not correlate with any of the three behavioral measures studied. Dopamine neurotransmitter markers indicated no genotypic difference in striatal tyrosine hydroxylase, DA transporter (DAT) or vesicular monoamine transporter 2 (VMAT2) immunoreactivity at any age. However, DA transport via DAT (starting at 12 months) and VMAT2 (starting at 3 months) as well as KCl‐stimulated DA release were reduced in Bdnf^+/? mice and declined with age suggesting an increasingly important role for BDNF in the release and uptake of DA with the aging process. These findings suggest that a BDNF expression deficit becomes more critical to dopaminergic dynamics and related behavioral activities with increasing age.     

Investigations of Δ 14C, δ 13C, and δ 15N in vertebrae of white shark (Carcharodon carcharias) from the eastern North Pacific Ocean

The white shark, Carcharodon carcharias, has a complex life history that is characterized by large scale movements and a highly variable diet. Estimates of age and growth for the white shark from the eastern North Pacific Ocean indicate they have a slow growth rate and a relatively high longevity. Age, growth, and longevity estimates useful for stock assessment and fishery models, however, require some form of validation. By counting vertebral growth band pairs, ages can be estimated, but because not all sharks deposit annual growth bands and many are not easily discernable, it is necessary to validate growth band periodicity with an independent method. Radiocarbon (¹⁴C) age validation uses the discrete ¹⁴C signal produced from thermonuclear testing in the 1950s and 1960s that is retained in skeletal structures as a time-specific marker. Growth band pairs in vertebrae, estimated as annual and spanning the 1930s to 1990s, were analyzed for Δ¹⁴C and stable carbon and nitrogen isotopes (δ¹³C and δ¹⁵N). The aim of this study was to evaluate the utility of ¹⁴C age validation for a wide-ranging species with a complex life history and to use stable isotope measurements in vertebrae as a means of resolving complexity introduced into the ¹⁴C chronology by ontogenetic shifts in diet and habitat. Stable isotopes provided useful trophic position information; however, validation of age estimates was confounded by what may have been some combination of the dietary source of carbon to the vertebrae, large-scale movement patterns, and steep ¹⁴C gradients with depth in the eastern North Pacific Ocean.     

Age,growth and mortality of invasive sharpbelly,Hemiculter leucisculus (Basilewski, 1855) in Erhai Lake,China

The sharpbelly Hemiculter leucisculus, an invasive species, has expanded its range throughout much of Asia and into the Middle East. However, little is known of its adaptive changes regarding life history traits such as age, growth and mortality that could possibly explain its success as an invasive species. A detailed study of the invasive sharpbelly was conducted based on 4539 samples collected from July 2009 to June 2011 in Erhai Lake, China. Standard length ranged from 4.3–19.1 cm for females and 4.6–12.3 cm for males. Length–weight relationships for females and males were significantly different and described as W = 0.0076SL^3.2608 and W = 0.0084SL^3.1901, respectively. Otoliths are ideal for age determination because of the single annulus formed each year. Based on marginal increment analysis, the total mean CV for age estimate between two readings was 3.55%. The von Bertalanffy growth curves computed by observed length‐at‐age data were expressed as L_t = 25.6 (1 ? e^{?0.176 (t + 1.347)}) for females and L_t = 16.4 (1 ? e^{?0.354 (t + 0.819)}) for males. According to the age, growth and mortality data, there are three possible reasons for H. leucisculus attaining such dominance within a short time in Erhai Lake. First, because of the simple age structure of this species: 97.58% of males were 1–2 years old with a maximum age of only 3 years; 93.14% of females were 1–3 years old, with a maximum age of 6 years. Second, females grew larger than males at any age. Third, instantaneous mortality rates were much higher for males (4.22 year^?1) than for females (1.17 year^?1).     

DNA methylation and chromatin accessibility predict age in the domestic dog

Across mammals, the epigenome is highly predictive of chronological age. These “epigenetic clocks,” most of which have been built using DNA methylation (DNAm) profiles, have gained traction as biomarkers of aging and organismal health. While the ability of DNAm to predict chronological age has been repeatedly demonstrated, the ability of other epigenetic features to predict age remains unclear. Here, we use two types of epigenetic information—DNAm, and chromatin accessibility as measured by ATAC-seq—to develop age predictors in peripheral blood mononuclear cells sampled from a population of domesticated dogs. We measured DNAm and ATAC-seq profiles for 71 dogs, building separate predictive clocks from each, as well as the combined dataset. We also use fluorescence-assisted cell sorting to quantify major lymphoid populations for each sample. We found that chromatin accessibility can accurately predict chronological age (R²_ATAC = 26%), though less accurately than the DNAm clock (R²_DNAm = 33%), and the clock built from the combined datasets was comparable to both (R²_combined = 29%). We also observed various populations of CD62L+ T cells significantly correlated with dog age. Finally, we found that all three clocks selected features that were in or near at least two protein-coding genes: BAIAP2 and SCARF2, both previously implicated in processes related to cognitive or neurological impairment. Taken together, these results highlight the potential of chromatin accessibility as a complementary epigenetic resource for modeling and investigating biologic age.     

Declining expression of a single epithelial cell‐autonomous gene accelerates age‐related thymic involution

Age‐related thymic involution may be triggered by gene expression changes in lymphohematopoietic and/or nonhematopoietic thymic epithelial cells (TECs). The role of epithelial cell‐autonomous gene FoxN1 may be involved in the process, but it is still a puzzle because of the shortage of evidence from gradual loss‐of‐function and exogenous gain‐of‐function studies. Using our recently generated loxP‐floxed‐FoxN1(fx) mouse carrying the ubiquitous CreER^T (uCreER^T) transgene with a low dose of spontaneous activation, which causes gradual FoxN1 deletion with age, we found that the uCreER^T‐fx/fx mice showed an accelerated age‐related thymic involution owing to progressive loss of FoxN1⁺ TECs. The thymic aging phenotypes were clearly observable as early as at 3–6 months of age, resembling the naturally aged (18–22‐month‐old) murine thymus. By intrathymically supplying aged wild‐type mice with exogenous FoxN1‐cDNA, thymic involution and defective peripheral CD4⁺ T‐cell function could be partially rescued. The results support the notion that decline of a single epithelial cell‐autonomous gene FoxN1 levels with age causes primary deterioration in TECs followed by impairment of the total postnatal thymic microenvironment, and potentially triggers age‐related thymic involution in mice.     

Neanderthal skeleton from Tabun: U-series data by gamma-ray spectrometry

The Neanderthal hominid Tabun C1, found in Israel by Garrod & Bate, was attributed to either layer B or C of their stratigraphic sequence. We have used gamma-ray spectrometry to determine the²³⁰Th/²³⁴U and²³¹Pa/²³⁵U ratios of two bones from this skeleton, the mandible and a femur. The ages calculated from these ratios depend on the uranium uptake history of the bones. Assuming a model of early U (EU) uptake the age of the Tabun C1 mandible is 34±5 ka. The EU age of the femur is 19±2 ka. The femur may have experienced continuous (linear) U uptake which would give an age of 33±4 ka, in agreement with the mandible's EU age, but implies marked inhomogeneity in U uptake history at the site. These new age estimates for the skeleton suggest that it was younger than deposits of layer C. This apparent age is less than those of other Neanderthals found in Israel, and distinctly younger than the ages of the Skhul and Qafzeh burials. This suggests that Neanderthals did not necessarily coexist with the earliest modern humans in the region. All of the more complete Neanderthal fossils from Israel are now dated to the cool period of the last glacial cycle, suggesting that Neanderthals may have arrived in this region as a result of the southward expansion of their habitable range. The young age determined for the Tabun skeleton would suggest that Neanderthals survived as late in the Levant as they did in Europe.     

Studies on DNA content, RNA synthesis, and DNA template activity in aging cells of Paramecium aurelia.

Investigations by Feulgen microspectrophotometry in Paramecium aurelia indicated that as fission age increased the amount of macronuclear DNA decreased. It was also found that the amount of RNA synthesis as determined by the in vivo incorporation of [³H]uridine decreased as the fission age increased. An alternative in situ assay of the DNA template activity determined by the RNA polymerase-catalyzed incorporation of [³H]UTP is described. The DNA template activity of older cells was shown to be significantly lower on a per cell basis than that of younger cells. The majority of this reduction was shown to be due to the gradual loss of DNA template with an increase in fission age. The specific activity of the DNA template, however, does show a small but significant decrease as the fission age of the cell increases.     

Lymphocyte subsets in human immunodeficiency virus-unexposed Brazilian individuals from birth to adulthood

Ethnic origin, genetics, gender and environmental factors have been shown to influence some immunologic indices, so that development of reference values for populations of different backgrounds may be necessary. We have determined the distribution of lymphocyte subsets in healthy Brazilian individuals from birth to adulthood. Lymphocyte subsets were determined using four-colour cytometry in a cross-sectional study of 463 human immunodeficiency virus-unexposed children and adults from birth through 49 years of age. Lymphocyte subsets varied according to age, as previously observed in other studies. However, total CD4⁺ T cell numbers were lower than what was described in the Pediatric AIDS Clinical Trials Group P1009 (PACTG P1009), which assessed an American population of predominantly African and Hispanic backgrounds until the 12-18 year age range, when values were comparable. Naïve percentages and absolute values of CD8⁺ T cells, as assessed by CD45RA expression, were also lower than the PACTG P1009 data for all analysed age ranges. CD38 expression on both CD4⁺ and CD8⁺ T cells was lower than the PACTG P1009 values, with a widening gap between the two studies at older age ranges. Different patterns of cell differentiation seem to occur in different settings and may have characteristic expression within each population.     

Electron spin resonance dating in paleoanthropology

Many archeological and paleoanthropological sites cannot be dated by well established and common dating techniques such as uranium series (U-series) or argon-argon (⁴⁰Ar/³⁹Ar) because of the lack of materials that are suitable for these techniques. Most sites, however, contain bones and teeth, and the latter can be used to obtain electron spin resonance (ESR) age estimates. The theoretical age range of ESR dating accuracy lies between a few thousand and more than a million years. In practice, continuing uranium accumulation increases the uncertainty of ESR age assessments in such a way that most age assignments beyond 300,000 years are very uncertain.     

Weaning at Anglo‐Saxon raunds: Implications for changing breastfeeding practice in britain over two millennia

This study investigated stable‐isotope ratio evidence of weaning for the late Anglo‐Saxon population of Raunds Furnells, Northamptonshire, UK. δ¹⁵N and δ¹³C values in rib collagen were obtained for individuals of different ages to assess the weaning age of infants within the population. A peak in δ¹⁵N values at about 2‐year‐old, followed by a decline in δ¹⁵N values until age three, indicates a change in diet at that age. This change in nitrogen isotope ratios corresponds with the mortality profile from the site, as well as with archaeological and documentary evidence on attitudes towards juveniles in the Anglo‐Saxon period. The pattern of δ¹³C values was less clear. Comparison of the predicted age of weaning to published data from sites dating from the Iron Age to the 19th century in Britain reveals a pattern of changing weaning practices over time, with increasingly earlier commencement and shorter periods of complementary feeding in more recent periods. Such a change has implications for the interpretation of socioeconomic changes during this period of British history, since earlier weaning is associated with decreased birth spacing, and could thus have contributed to population growth. Am J Phys Anthropol 151:604–612, 2013. © 2013 Wiley Periodicals, Inc.     

大兴安岭5种典型林型森林生物碳储量

森林生态系统是陆地生态系统的重要碳库,森林生态系统的生物碳储量作为森林生态系统碳库的重要组成部分,对全球碳循环与碳平衡产生重要作用。以大兴安岭5种典型林型为研究对象,结合森林资源清查资料,采用地理信息技术(GIS),将5种林型分龄组分别对乔木层、林下的灌木层、草本层和凋落物层各组分的单位面积生物量、含碳率和生物碳储量进行测定和计量估算,并从林分水平上,采用分龄组的方法,计量估算了生物碳储量。结果表明:大兴安岭5种典型林型不同龄组的生物碳储量分别为:兴安落叶松幼龄林、中龄林、近熟林和成熟林的生物碳储量分别为15.20、50.96、95.80t/hm2和109.33t/hm2;白桦幼龄林、中龄林、近熟林和成熟林的生物碳储量分别为15.36、30.67、41.62t/hm2和64.35t/hm2;樟子松幼龄林、中龄林、近熟林和成熟林的生物碳储量分别为29.89、59.92、90.01t/hm2和117.08t/hm2;蒙古栎幼龄林、中龄林、近熟林和成熟林的生物碳储量分别为11.17、11.90、34.94t/hm2和59.49t/hm2;山杨幼龄林、中龄林、近熟林和成熟林的生物碳储量分别为21.81、28.58、42.84t/hm2和64.39t/hm2。研究发现:5种典型林型不同龄组的森林生物碳储量均随着林龄(幼龄林、中龄林、近熟林和成熟林)的增长而增加,但不同林型的碳汇功能存在差异,同一种林型在不同林龄的生物碳储量增幅差异亦较大。尤其是大兴安岭目前林分质量比较差,幼龄林和中龄林所占的比重较大,若能对现有林分加以更好地抚育和管理,该区森林植被仍具有较大的碳汇潜力,碳汇功能将进一步增强,大兴安岭在国家的生态功能区建设中将发挥更重要的碳汇功能,对此提出了森林生态系统碳增汇管理策略与管理路径。研究结果为正确认识森林生物碳储量对区域碳平衡及生态环境的影响具有重要意义,以及在未来营林、造林活动中充分发挥人工林碳汇效应提供参考依据。     

Heritability of metabolic syndrome traits in a large population-based sample

Heritability estimates of metabolic syndrome traits vary widely across studies. Some studies have suggested that the contribution of genes may vary with age or sex. We estimated the heritability of 11 metabolic syndrome-related traits and height as a function of age and sex in a large population-based sample of twin families (N = 2,792–27,021, for different traits). A moderate-to-high heritability was found for all traits [from H² = 0.47 (insulin) to H² = 0.78 (BMI)]. The broad-sense heritability (H²) showed little variation between age groups in women; it differed somewhat more in men (e.g., for glucose, H² = 0.61 in young females, H² = 0.56 in older females, H² = 0.64 in young males, and H²= 0.27 in older males). While nonadditive genetic effects explained little variation in the younger subjects, nonadditive genetic effects became more important at a greater age. Our findings show that in an unselected sample (age range, ∼18–98 years), the genetic contribution to individual differences in metabolic syndrome traits is moderate to large in both sexes and across age. Although the prevalence of the metabolic syndrome has greatly increased in the past decades due to lifestyle changes, our study indicates that most of the variation in metabolic syndrome traits between individuals is due to genetic differences.     

Composition and structure of a chronosequence of young, mixed-species forests in southeastern Ohio, USA

Clearcutting, a commonly used silvicultural practice in southeastern Ohio, often results in a forest stand with a different species composition than the parent stand. The time frames during which shifts in species composition occur on different sites are unclear. While some studies have documented species composition at specific points in time, none have attempted to examine differences throughout the first decades of stand development. This study focused on the early successional dynamics of young, mixed-species forests of southeastern Ohio. Species compositions were examined across a chronosequence of sixteen stands that developed following clearcutting. Stand ages ranged from six to 26 years. The sample was limited to dry-mesic hardwood forests on southerly aspects and on soils derived from residuum or colluvium. Across the chronosequence, stand density ranged from 17 636 stems ha^-1 at age 6 to 2759 stems ha^-1 at age 26, and basal area ranged from 8.2 m² ha^-1 to 22.1 m² ha^-1. Clumps comprised a substantial portion of the total stand density and basal area. At age 6–8 years after clearcutting, clumped stems accounted for 35.1% of the density and 48.2% of the basal area. At age 26 years, these proportions were 25.7% and 29.4%, respectively. Clumped stems were significantly larger (p<0.05) than non-clumped stems at each age group except 26 years. Total Quercus spp. density was greatest at age 6–8 years (3386 stems ha^-1), and least at age 26 years (581 stems ha^-1). When considered as a proportion of the total stand, however, the proportion was relatively stable, averaging 21.3%. However, importance value (IV=[relative density + relative basal area]/2) of Quercus in the upper canopy (dominant and codominant crown classes) was twice as much (72%) at age 26 years compared to age 6–8 years (35%). Quercus prinus L. was the major species across the chronosequence. For all age groups except 18–20 years. Q. prinus IV was the highest of any individual species in the upper canopy, and it ranged from 27 in the youngest stands (6–8 years) to 69 in the oldest stand (26 years). Within the intermediate crown class, the IV of Q. prinus equaled or exceeded those of all other species, except for the 18–20 year age group where it was second to A. rubrum. Quercus alba L. and Quercus velutina Lam. were minor components at age 26 years, although they dominated a comparison sample of six mature stands of the same ecosystem type. Liriodendron tulipifera L. was abundant 6–8 years after clearcutting, but nearly absent at age 26 years. Acer rubrum L. was the major species in both the intermediate and overtopped crown classes throughout the chronosequence. As gaps in the canopy occur. A. rubrum may become a more common species within the dominant-codominant crown class.     

NAD+ controls neural stem cell fate in the aging brain

Loss of the coenzyme NAD⁺, which is required for many energy‐dependent cellular processes, has emerged as a potentially unifying mechanism for age‐related conditions. A study in this issue of The EMBO Journal identifies a novel link between depletion of NAD⁺ and age‐associated loss of proliferating adult neural stem/progenitor cells in the murine brain (Stein & Imai, 2014 ). These data have important implications for how brain function might decline with age.