Age-related changes in serum amino acids concentrations in healthy individuals

Abstract Background: Serum amino acids, part of a pool of free amino acids, are influenced by metabolism and disease. Few reports exist describing their function and concentrations in serum. Our study aimed to determine age- and gender-related differences in serum amino acid concentrations in healthy Japanese patients, focusing on their inclusion in body proteins. Methods: Healthy patients with normal liver and kidney function were selected based on biochemical variables. Serum amino acid concentrations in 23-88-year-old patients (312 males, 252 females; 52.1±15.0 years) were evaluated to determine the normal values and to clarify the differences in concentration. The patients were divided into 11 groups according to their gender and age (in 5-year increments), and serum amino acid concentrations were determined as the normal values for each group. Results: Some amino acids increased or decreased with age. Values of leucine, threonine, methionine, histidine, glycine, serine and taurine decreased with age in males, whereas, those of threonine and serine decreased with age in females (p<0.05). In contrast, values of phenylalanine, aspartate, asparagine, glutamate, alanine, citrulline, ornithine, arginine and tyrosine increased with age in males, whereas, values of phenylalanine, lysine, asparagine, glutamate, glutamine, alanine, citrulline, ornithine, arginine, tyrosine and proline increased with age in females (p<0.05). Conclusions: We clarified basic trends of age- and gender-related amino acid concentrations in serum. In normal healthy Japanese people who ate normally and lived an independent life, there are significant age- and gender-related differences.     

Age-related changes in the level of serum bone markers in healthy children

Age-related changes in the blood level of bone metabolic markers were compared in healthy children living in different geographical regions. The absolute value of carboxy-terminal telopeptide of type 1 collagen type 1 (beta-CrossLaps) and that of total procollagen type 1 amino-terminal propeptide (PINP) were found to depend on living conditions and the nature of changes in the serum markers of bone metabolism was related to the processes of natural growth and development in children. A child's individual growth curve can be used to identify target groups for the prevention of osteopenia.     

Dysmenorrhoea is associated with central changes in otherwise healthy women

Patients with chronic pain conditions demonstrate altered central processing of experimental noxious stimuli, dysfunction of the hypothalamic-pituitary-adrenal axis, and reduced quality of life. Dysmenorrhoea is not considered a chronic pain condition, but is associated with enhanced behavioural responses to experimental noxious stimuli. We used behavioural measures, functional magnetic resonance imaging, and serum steroid hormone levels to investigate the response to experimental thermal stimuli in otherwise healthy women, with and without dysmenorrhoea. Women with dysmenorrhoea reported increased pain to noxious stimulation of the arm and abdomen throughout the menstrual cycle; no menstrual cycle effect was observed in either group. During menstruation, deactivation of brain regions in response to noxious stimulation was observed in control women but not in women with dysmenorrhoea. Without background pain (ie, in nonmenstrual phases), activity in the entorhinal cortex appeared to mediate the increased responses in women with dysmenorrhoea. Mean cortisol was significantly lower in women with dysmenorrhoea and was negatively correlated with the duration of the symptom. Additionally, women with dysmenorrhoea reported significantly lower physical but not mental quality of life. Thus, many features of chronic pain conditions are also seen in women with dysmenorrhoea: specifically a reduction in quality of life, suppression of the hypothalamic-pituitary-adrenal axis, and alterations in the central processing of experimental noxious stimuli. These alterations persist when there is no background pain and occur in response to stimuli at a site distant from that of the clinical pain. These findings indicate the potential importance of early and adequate treatment of dysmenorrhoea.     

Age-related changes in bone turnover markers and ovarian hormones in premenopausal and postmenopausal Indian women

This study characterizes age-related changes in bone turnover markers in relation to ovarian hormones. The data (N = 236) were divided into 5-year age bands and three groups: premenopausal (Group I, N = 139), perimenopausal (Group II, N = 30), and postmenopausal (Group III, N = 67). Age-related increases in mean parathyroid hormone (PTH), osteocalcin (OC), and collagen telopeptide (CTx) levels were observed. Women in Group II (N = 37) with osteopenia had lower levels of E1G (P<0.001) with normal FSH levels as compared to 50 women in the same group with normal bone mineral density (BMD). Their mean OC levels were reduced (P<0.05) and CTx levels were significantly elevated (P<0.01). The mean E1G levels were significantly lower (P<0.001) and mean CTx levels were significantly higher (P<0.001) in 30 perimenopausal women (Group II) compared to premenopausal women. In 28 postmenopausal women (group III) the mean BMD levels and E1G were significantly lower (P<0.001) with elevated FSH levels (P<0.001). Increased CTx levels (P<0.0001) reflected a higher rate of bone resorption. These observations suggest that perimenopausal women with low E1G, elevated FSH should be screened for osteoporosis, and it may be valid to combine simultaneous measurements of bone turnover markers with ovarian hormones when screening women at risk for osteoporosis.     

Age-related differences in hs-cTnI concentration in healthy adults

BackgroundBecause the 99th percentile is of such importance in defining myocardial injury and myocardial infarction, it is important to know whether there are real age-related differences in troponin 99th percentiles.MethodsWe went to our database from the Canberra Heart Study where 1062 apparently healthy subjects were extensively screened for occult cardiac disease, and looking at persons aged <65 years and >65 years, for men and women separately, we compared a variety of cutpoints from the 99th percentile down to the 50th percentile.ResultsWith our rigorous criteria for defining cardiac health, we excluded 67.2% of males aged >65 years and 53.8% of women aged 65 years and older. Even with these rigorous exclusions we found that at every cutpoint examined between the 99th percentile and the 50th percentile, persons aged <65 years had lower troponin I concentrations that persons aged 65 years and older. Similarly, at every cutpoint examined, women had lower troponin I concentrations than did men.For the 4 separate groups examined (men and women, age < 65 years and 65 years and older) after the exclusions of persons with subclinical cardiac disease, the distributions were not significantly different to a Gaussian distribution.ConclusionsWith the rigorous exclusions of persons with subclinical cardiac disease, and the fact that our populations have a Gaussian distribution, our data suggests that age-related hs-cTnI concentrations are real. This has important implications particularly when assessing older persons in the Emergency Department.     

Age-related changes in plasma coenzyme Q10 concentrations and redox state in apparently healthy children and adults

BACKGROUND: Coenzyme Q10 (CoQ) is an endogenous enzyme cofactor, which may provide protective benefits as an antioxidant. Because age-related CoQ changes and deficiency states have been described, there is a need to establish normal ranges in healthy children. The objectives of this study are to determine if age-related differences in reduced CoQ (ubiquinol), oxidized CoQ (ubiquinone), and CoQ redox state exist in childhood, and to establish reference intervals for these analytes in healthy children. METHODS: Apparently healthy children (n=68) were selected from individuals with no history of current acute illness, medically diagnosed disease, or current medication treatment. Self-reported healthy adults (n=106) were selected from the ongoing Princeton Follow-up Study in greater Cincinnati. Participants were assessed for lipid profiles, ubiquinol concentration, ubiquinone concentration, total CoQ concentration, and CoQ redox ratio. RESULTS: Mean total CoQ and ubiquinol concentrations are similar in younger children (0.2-7.6 years) and adults (29-78 years); however, lipid-adjusted total CoQ concentrations are significantly increased in younger children. Also CoQ redox ratio is significantly increased in younger and older children compared with adults. CONCLUSIONS: Elevated CoQ and redox ratios in children may be an indication of oxidative stress effects, which are associated with early development of coronary heart disease.     

Age-related changes in muscles and joints

Aging muscle and joint changes can have a tremendous impact on the functionality of elderly people with and without disabilities. Studies in animal models have shown some potentially beneficial interventions (eg, gene therapy). Further research is needed to ascertain their benefits in humans. A better understanding of mechanisms by which skeletal muscle and joint changes take place in a geriatric population will be helpful to find reasonable ways to prevent age-related change and improve disability. Although some agents have been reported to have significant positive effects, further studies are needed to determine long-term side effects. More information is needed with respect to the changes in muscles and joints in various disabilities.     

Age-related balance changes in hearing-impaired children

This study compared balance skills of hearing-impaired children with those of hearing children in order to determine whether a deficit in balance exists in hearing-impaired children and to ascertain whether this deficit is age-related. Twenty-eight hearing-impaired subjects were chosen as a sample of convenience from the Pennsylvania School for the Deaf and placed into one of three age groups. Ten subjects were in the 4.5 to 6.5-year-old age group, 8 in the 8- to 10-year-old age group, and 10 in the 12.5 to 14.5-year-old age group. Selection criteria included bilateral sensorineural hearing loss of greater than or equal to 65 dB and normal intelligence (IQ greater than or equal to 80). Balance was measured by the use of the Balance subtest of the Bruininks-Oseretsky Test of Motor Proficiency. For each age group, a z test was used to compare the subjects' scores with the Balance subtest standard scores. The results showed that for each age group, the mean score for the hearing-impaired children was lower than the standard score. Both older groups had significantly higher scores than the youngest group, but the mean scores of the older groups were not significantly different. No difference between the subjects' balance scores and the Balance subtest standard scores was found among the age groups, suggesting that the balance deficit was not age-related. Gender differences were not found for balance scores.     

部分慢性病症患病率与年龄的相关性

目的探讨慢性疾病年龄相关性改变的规律。方法对某大型企业在职和离退休职工进行血糖、血症、血尿酸、乙型肝炎病毒5项指标、心电图、B型超声波、X线胸片、血压和眼科检查。结果患病率占前15位的病症分别是高血压(37.7%)、脂肪肝(32.7%)、高血脂症(21.4%)、心肌缺血(16.7%)、肝囊肿(14.1%)、白内障(14.0%)、肝胆结石(7.8%)、高血糖(6.3%)、心脏传导阻滞(6.1%)、肺结核(5.9%)、胆囊炎(5.6%)、胆囊息肉(5.5%)、乙型肝炎病毒及其表面抗原携带(4.0%)、心律失常(2.6%)和高尿酸血症(0.6%)。多数疾病患病率与年龄正相关,但改变的模式差异很大。结论高血压、高血脂症、心肌缺血为部分企业人群中的主要慢性疾病,三者的患病率均呈年龄相关性增加。     

Age-related changes in the hemostatic system

Summary The increased incidence of arterial thromboembolism in the elderly has prompted investigation of age-related changes in the hemostatic system. Aging is associated with increased plasma levels of fibrinogen, factor VII and factor VIII, which have been shown to be risk factors for thrombotic disease in five large epidemiological studies. An increased responsiveness to different aggregating stimuli, elevated levels of β-thromboglobulin and an increased production of thromboxane A₂ were reported in the platelets of the elderly. These alterations are associated with modifications of platelet membrane lipid composition (namely an increase in the cholesterol/phospholipid ratio and a decrease in linoleic acid) with possible related changes in membrane fluidity. Moreover, a decrease in the number of platelet prostacyclin and thromboxane A₂ receptors was observed with aging. Fibrinolytic activity is impaired in the elderly, probably due to an increase in plasminogen activator inhibitor 1. Interestingly, hypercoagulability has been demonstrated by an increase in the activation markers of the coagulation cascade (mainly fibrinopeptide A and prothrombin activation fragment F 1+2). Finally, clinical and experimental evidence suggests that endothelium could play a central role in hemostatic alterations which determine a thrombophilic state in the elderly.     

Age-related changes in enteric neuromuscular transmission

Proximal and distal rat small intestine from 4-, 5- and 6-month-old rats were cut into strips measuring 6.0 X 10.0 mm. Longitudinal strips were cut along the oral-caudal axis of the intestine while circular strips were cut 90 degrees to that axis. The strips were stretched to their optimum lengths and subjected to electrical field stimulation (0.1-1.0 msec pulse duration, 30-270 mA, 1-26 Hz) in the presence of Krebs' solution and Krebs' solution plus 10(-6) M atropine. Field stimulation produced atropine-sensitive and atropine-resistant contractions in these tissues. Significant differences among the three groups were found in the amplitudes of atropine-sensitive contractions in strips from proximal longitudinal muscle. The 6-month-old animals showed the highest amplitude contractions and the 4-month-old the lowest, whereas the 5-month-old animals showed contractions that were intermediate in amplitude. No significant differences were noted among the atropine-resistant contractions. Field stimulation delivered at pulse durations of 5.0 and 50.0 msec in the presence of neural blockade with tetrodotoxin (5 X 10(-6) M) produced similar contraction amplitudes among the three groups. These results show that tension development produced by field stimulation of the proximal intestine increases significantly with age. The increases appear to be due to age-related differences in cholinergic neuromuscular transmission.     

Novel factor VII gene mutations in six families with hereditary coagulation factor VII deficiency

IntroductionHereditary human coagulation factor VII (FVII) deficiency is an inherited autosomal recessive hemorrhagic disease involving mutations in the F7 gene. The sites and types of F7 mutations may influence the coagulation activities of plasma FVII (FVII: C) and severity of hemorrhage symptoms. However, the specific mutations that impact FVII activity are not completely known.MethodsWe tested the coagulation functions and plasma activities of FVII in seven patients recruited from six families with hereditary FVII deficiency and sequenced the F7 gene of the patients and their families. Then, we analyzed the genetic information from the six families and predicted the structures of the mutated proteins.ResultsIn this study, we detected 11 F7 mutations, including four novel mutations, in which the mutations p.Phe84Ser and p.Gly156Cys encoded the Gla and EGF domains of FVII, respectively, while the mutation p.Ser339Leu encoded the recognition site of the enzymatic protein and maintained the conformation of the catalytic domain structure. Meanwhile, the mutation in the 5′ untranslated region (UTR) was closely associated with the mRNA regulatory sequence.ConclusionWe have identified novel genetic mutations and performed pedigree analysis that shed light on the pathogenesis of hereditary human coagulation FVII deficiency and may contribute to the development of treatments for this disease.     

Coagulation factor VII gene haplotypes, obesity-related traits, and cardiovascular risk in young women

BACKGROUND: Associations between common F7 haplotypes, plasma factor VII (FVII) levels, and cardiovascular risk have recently been reported in population studies involving predominantly European men. METHODS: We assessed associations between F7 haplotypes and cardiovascular risk in two US population-based studies: a case-control study of these alleles related to a decreased risk of arterial thrombotic outcomes such as myocardial infarction (MI) in young-to-middle-aged women (n = 671), and a cohort study of cardiovascular disease risk factors in young women (n = 1040). RESULTS: The high-expression F7 haplotype B (containing the promoter variant allele -402A) was associated with an increased FVII level among controls, but not with MI risk. Women carrying a> or =1 copy of the low FVII expression level haplotype C (containing the -401T/-323del/-122C and Gln353 alleles) had decreased FVII levels and decreased risk of MI (odds ratio 0.54, 95% CI 0.31-0.93) compared with women homozygous for the most common haplotype A. Haplotype C was also associated with a decreased body mass index (BMI) and an increased high-density lipoprotein (HDL) cholesterol level, but not with MI risk after adjustment for these metabolic risk factors. In a cohort study composed of young US women, individuals homozygous for haplotype C had a lower BMI and lower systolic blood pressure, but the association between the F7 haplotype and HDL cholesterol was not confirmed. CONCLUSION: Common FVII haplotypes may contribute to the risk of MI in women, but the mechanisms appear complex. The association between F7 haplotypes and MI susceptibility may be mediated in part through an influence on atherogenic risk factors such as BMI.