Laboratory parameters in centenarians of Italian ancestry

Studies aimed at collecting reference parameters for haematochemical analysis in the elderly are scarce and for the oldest old subjects even more rare. In order to establish the reference values for the most common laboratory text in long living individuals, we measured haematochemical parameters in >100 years old subjects and in aged subjects as control. Six hundred and two centenarians accepted to be enrolled in the study. A case history containing the complete anamnesis, clinical examinations, evaluation of the clinical cognitive and functional tests, was prepared for each centenarian. Blood samples from 120>100 years old subjects free of chronic or acute Illness (i.e. Alzheimer's disease, metabolic diseases, cardiovascular disease, stroke, neoplastic and infectious diseases) were analysed. A population of 381 healthy old subjects (age range 65-85 years old), recruited in the same geographic areas and with the same clinical characteristic of the health centenarians, was utilized as control. Significant differences were observed for blood glucose, ALT, cholesterol and platelet levels, reduced in centenarians respect to the old subjects, whereas blood urea nitrogen levels were found significantly increased in centenarians. In conclusion, reference values of the healthy adults can generally been utilized also for the healthy oldest old group, with the notable exception of the above mentioned laboratory parameters that appear to be modified in long living subjects.     

Helicobacter antibodies in Finnish centenarians.

BACKGROUND: The prevalence of helicobacter antibodies increases with age and, in many developed countries, is highest in people born before 1940. Data on very old subjects are, however, limited. In this study we wanted to determine whether the age-related increase in the seroprevalence of H. pylori infection continues even in the oldest age group alive in Finland, the centenarians. METHODS: Sera from 173 subjects (93% of all centenarians alive in Finland in 1991) were available for the present study. IgG and IgA antibodies against H. pylori were determined by an in-house enzyme immunoassay. To estimate the influence of atrophic gastritis on the prevalence of helicobacter antibodies, serum pepsinogen I (PG I) concentrations and parietal cell antibodies (PCAs) were measured by an enzyme immunoassay and indirect immunofluorescence, respectively. RESULTS: The prevalence of helicobacter antibodies in Finnish centenarians was 66%. Low PG I values (<28 microg/l) were found in 36% and positive PCAs in 16% of the subjects studied. The prevalence of PCAs was especially high (50%) in H. pylori-negative subjects with low PG I values, suggesting severe gastric atrophy. CONCLUSIONS: The age-related increase in H. pylori seroprevalence did not continue in the oldest age group alive in Finland. This may be explained partly by a relatively high frequency of atrophic gastritis (as suggested by low PG I values) in H. pylori-negative centenarians, but other factors--such as selective H. pylori-related mortality--may also have contributed to the fairly low seroprevalence (66%) observed.     

Diabetes mellitus in centenarians

Objectives

To describe the prevalence of diabetes mellitus (DM) in centenarians.

Design

Cross‐sectional, population‐based.

Setting

Forty‐four counties in northern Georgia.

Participants

Two hundred forty‐four centenarians (aged 98–108, 15.8% male, 20.5% African American, 38.0% community dwelling) from the Georgia Centenarian Study (2001–2009).

Measurements

Nonfasting blood samples assessed glycosylated hemoglobin (HbA_1c) and relevant clinical parameters. Demographic, diagnosis, and DM complication covariates were assessed.

Results

12.5% of centenarians were known to have DM. DM was more prevalent in African Americans (27.7%) than whites (8.6%, P < .001). There were no differences between men (16.7%) and women (11.7%, P = .41) or between centenarians living in the community (10.2%) and in facilities (13.9%, P = .54). DM was more prevalent in overweight and obese (23.1%) than nonoverweight (7.1%, P = .002) centenarians. Anemia (78.6% vs 48.3%, P = .004) and hypertension (79.3% vs 58.6%, P = .04) were more prevalent in centenarians with DM than in those without, and centenarians with DM took more nonhypoglycemic medications (8.6 vs 7.0, P = .02). No centenarians with HbA_1c of less than 6.5% had random serum glucose levels greater than 200 mg/dL. DM was not associated with 12‐month all‐cause mortality, visual impairment, amputations, cardiovascular disease, or neuropathy. Thirty‐seven percent of centenarians reported onset before age 80 (survivors), 47% between age 80 and 97 (delayers), and 15% aged 98 and older (escapers).

Conclusion

Diabetes mellitus is a risk factor for cardiovascular disease and mortality but is seen in persons who live into very old age. Aside from higher rates of anemia and use of more medications, few clinical correlates of DM were observed in centenarians.     

Hemopoiesis in healthy old people and centenarians: well-maintained responsiveness of CD34+ cells to hemopoietic growth factors and remodeling of cytokine network

In vitro hemopoiesis and hemopoietic cytokines production were evaluated in 9 centenarians (median age 100.5 years, age range: 100-104 years), 10 old people (median age: 71 years, age range: 66-73 years), and 10 young people (median age: 35 years, age range: 30-45 years), all carefully selected for their healthy status. The main findings were the following: (i) a trend towards a decreased absolute number of CD34+ progenitor cells in the peripheral blood of old people and centenarians, in comparison to young subjects; (ii) a well-preserved capability of CD34+ cells from old people and centenarians to respond to hemopoietic cytokines, and to form erythroid (BFU-E), granulocyte-macrophagic (CFU-GM), and mixed colonies (CFU-GEMM) in a way (number, size, and morphology) indistinguishable from that of young subjects; (iii) an age-related decreased in vitro production of granulocyte-macrophagic colony-stimulating factor (GM-CSF) and a decreased production of interleukin-3 (IL-3) in centenarians by phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMC); (iv) a linear increase of the serum level of stem cell factor (SCF), measured in the above-mentioned subjects and in 65 additional subjects, including 4 centenarians. These data suggest that basal hematopoietic potential is well preserved in healthy centenarians, and that the hemopoietic cytokine network undergoes a complex remodeling with age.     

Thyroid function in physiological aging and in centenarians: possible relationships with some nutritional markers.

Changes in thyroid function are often described in elderly subjects; however, their pathophysiologic significance and the possible contributory role of both malnutrition and nonthyroidal illness are still debated. The aim of this cross-sectional study was to investigate thyroid function in relationship to some markers of the nutritional status in a group of healthy old subjects and in some centenarians living in nursing homes. Patients included 24 clinically healthy elderly women (age, 71 to 93 years), 24 clinically healthy centenarian women (age, 100 to 106 years), and 20 healthy young subjects (age, 22 to 33 years). Blood samples were drawn from each subject for the evaluation of thyroid-stimulating hormone (TSH), free triiodothyronine (FT(3)), free thyroxine (FT(4),) reverseT(3) (rT3), autoantibodies against thyroglobulin (AbTg) and against thyroid peroxidase (AbTPO), and for the main humoral nutritional markers. TSH and thyroid hormones were assayed by fluoroimmunometric method; rT3 and thyroid autoantibodies by radioimmunoassay (RIA) and enzyme chemiluminescent immunometric assay, respectively. The mean values of TSH, FT(3) and FT(4) fell within the normal range in both groups. However, by comparison to old controls, in centenarian subjects, TSH levels were significantly lower, whereas rT(3) concentrations were slightly, but significantly, increased. Autoantibodies positivity was found in 4.16% of centenarians and in 10.4% and 13.6% of old and young controls. Thus, the incidence of thyroid autoantibodies was lower in centenarians than in old controls. Except for transferrin, lower than the normal range in centenarians, all of the other nutritional markers evaluated fell within the laboratory range of normality. Total cholesterol levels were significantly reduced in centenarians by comparison to old controls. Our results showed an age-related decline of the TSH levels and a significant increase of the rT(3) concentrations in centenarians by comparison to old controls. These findings may be related to an age-dependent reduction of the 5'-deiodinase activity rather than to important changes of nutritional markers.     

Lipoprotein metabolism in Japanese centenarians: effects of apolipoprotein E polymorphism and nutritional status

OBJECTIVES: To assess the complex interaction of apolipoprotein (apo) E polymorphisms and environmental factors on lipoprotein profile in centenarians. DESIGN: Cross-sectional analysis. SETTING: Tokyo metropolitan area. PARTICIPANTS: Seventy-five centenarians and 73 healthy older volunteers (mean age 63.1 +/- 10.0) living in the Tokyo metropolitan area. MEASUREMENTS: Plasma lipids and lipoproteins, cholesteryl ester transfer protein mass, apo E phenotype, body mass index, nutritional indices (serum albumin, prealbumin, transferrin), dietary intake, inflammation markers (C-reactive protein (CRP), interleukin-6 (IL-6)), activities of daily living, and cognitive function. RESULTS: In comparison with older people, the centenarians had low concentrations of total and low-density lipoprotein cholesterol (LDL-C) and a relative predominance of high-density lipoprotein 2 cholesterol. No environmental factor, except the number of apo E epsilon2 alleles, was a significant determinant of LDL-C and apo B, suggesting that the low apo B-containing lipoprotein in centenarians may be attributable to a genetic cause. Centenarians had elevated levels of lipoprotein (a) and decreased high-density lipoprotein cholesterol (HDL-C), which seem to be an unfavorable lipoprotein profile. Lower levels of HDL-C in the centenarians were associated with decreased serum albumin, elevated CRP and IL-6 levels, and cognitive impairment, suggesting that HDL-C could be a sensitive marker for frailty and comorbidity in the oldest old. CONCLUSIONS: Low levels of apo B-containing lipoproteins attributable to a genetic cause may be advantageous for longevity. Lipoprotein profiles in centenarians were consistently related to the subjects' nutritional status, inflammation markers, and apo E polymorphisms. The results provide evidence for the importance of maintaining nutritional status in the very old.     

Hemostasis factors and aging

With advancing age, an increasing number of healthy individuals have laboratory signs of heightened coagulation enzyme activity. Such biochemical hypercoagulability might be the basis of either the increased thrombotic tendency occurring with age or a harmless manifestation of this process. Centenarians had striking signs of heightened coagulation enzyme activity, accompanied by signs of enhanced formation of fibrin and secondary hyperfibrinolysis. Plasma concentrations of fibrinogen and factor VIII were higher than in controls, whereas other coagulation factors were not elevated. It is of interest that centenarians have a significantly higher frequency than young individuals of the high risk 4G allele of the PAI-1-675 (4G/5G) polymorphism, mutant factor V (Arg506Gln) and prothrombin gene G20210A mutation. Von Willebrand factor (VWF), a well-known independent predictor of atherothrombotic disease, was increased in centenarians, independently of the blood group, confirming the previous results of a state of hypercoagulability. The finding that the VWF cleaving proteases levels are low when VWF levels are high in centenarians could be a corollary of the previous described paradox of successful aging, adding another marker of increased risk of atherothrombosis to the scenario. Alike, high prevalence of anti-phospholipids antibodies, not associated with an anti-phospholipid syndrome has been described in centenarians. In conclusion, the data show the oldest old do not escape the state of hypercoagulability associated with aging, but that this phenomenon is compatible with health and longevity. Hence, high plasma levels of the coagulation activation markers in older populations do not necessarily mirror a high risk of arterial or venous thrombosis.     

Hypertension in a group of centenarians

The aim of the present study was to evaluate the frequency of hypertension in a group of extremely old persons: 73 centenarians resident in Calabria were studied, aged 100-110 years, (mean age 102.95 +/- 2.0), 54 women (73.9%) and 19 men (26.1%), in the period January 1st and April 30th, 1994. All the centenarians were visited at their homes. Hypertensive centenarians were 14 (19.1%), women 12 (85.7%) and men 2 (14.3%). Even if blood pressure progressively increases with age, we have not found it in centenarians. The lesser frequency of hypertension in centenarians certainly depends on genetic and constitutional factors, but also their way of life and alimentary habits (decreased sodium intake, increase of calcium and potassium intake), as we have proven in a recent work, could be determinant. Moreover, the presence of hypertensive centenarians might mean that hypertension does not prevent to reach an age by far above the average, if it is the only risk factor.     

Physical activity and the risk of dementia in oldest old

OBJECTIVE: This study evaluated the protective role of physical activity (PA) against cognitive impairment (CI) in the oldest old (age >/= 85). METHOD: Prospective data on 66 optimally healthy, oldest old adults (mean age 88.5) were analyzed using survival analysis. RESULTS: In all, 12 men and 11 women reported exercising > 4 hours per week, and 38 participants developed CI (mean onset age 93; mean follow-up 4.7 years). The effect of exercise was modified by gender. In more active women (> 4 hours/week), the risk of CI was reduced by 88% (95% confidence interval 0.03, 0.41) compared to those less active. Less active women had 2 times the incidence rate of CI compared to less active men and almost 5 times the rate compared to active women. DISCUSSION: This study demonstrates the beneficial effects of exercise on healthy brain aging even in the oldest old and emphasizes the importance of increasing PA in older women.     

2型糖尿病合并衰弱和肌少症的机制与治疗

中国人群2型糖尿病总体患病率约9.1%。与正常人相比,60岁时确诊2型糖尿病的患者,其预期寿命减少7.3～9.5年,维持良好生命质量的时间减少11.1～13.8年。对于老年糖尿病患者,保持良好的功能状态至关重要。衰弱是一种常见的老年综合征,是影响老年人功能状态的重要因素,是老年人残疾、死亡和住院等不良健康结局的强预测因...     

Regional aging and longevity characteristics in China

The factors that influence the length of human life are complex and longevity remains a controversial topic, particularly in China. This paper demonstrates the spatial patterns and changes of the elderly group (65 years old and over), the oldest old (80 years old and over) and the centenarians in China in the last decade, analyzes the influence of economic development on aging, and in the end, using a case study, explores the characteristics of the centenarians’ behavior. The results indicate that high elderly and the oldest old proportions are more common in regions with higher socio-economic development and that have a favorable climate. Centenarian distribution pattern is less influenced by economic but only for few regions. Lifestyle factors, such as sufficient sleep, positive mental state and a light diet are also largely found among the centenarian group.     

Suggestions from a centenarian study--aging and inflammation

With the numbers of elderly increasing rapidly, it is important for both individuals and society that the oldest old maintains autonomy. To know how to attain successful aging, we investigate the status of centenarians. The characteristics of centenarians in Tokyo is 1) low level of nutritional parameters, 2) low level of cholesterol and HDL-cholesterol, 3) low level of red blood cells and hemoglobin, 4) high level of CRP, 5) high level of homocysteine, 6) high level of von Willbrand factor. The incidence of dementia is 59.3%. Are these characteristics due to aging itself or other factors? We examined the effect of nutritional status, inflammation and level of homocysteine on the characteristics. The level of albumin is associated with serum level of lipid, RBC, ADL and cognitive function. The level of CRP is related to the level of albumin, suggesting that inflammation is related to nutritional status. The level of homocysteine is associated with the level of von Willbrand factor, suggesting that homocysteine is related to endothelial injury. From these data, we propose the hypothesis that proinflammatory status is associated with aging, resulting in a part of characteristics of centenarians. Homocysteine is partly responsible for endothelial injury. Intervention to suppress proinflammatory status and homocysteine level may promote QOL in the oldest old.     

Lower platelet count in healthy centenarians correlates with dispersion of the QT interval

BACKGROUND AND AIMS: Centenarians display a lower incidence of vascular ischemic events. A high platelet count and increased QT dispersion (QTd) represents a risk factor for cardiovascular events. The aim of this study was to evaluate platelet count and QTd in healthy centenarians and to establish correlations between these two indices. METHODS: 16 healthy centenarians (4 males, 12 females, range 100-105 years) living in a municipality of Eastern Sicily, and 40 healthy control subjects, divided into two groups: group A (N=20), age range 45-65 years, 7 males, 13 females; and group B (N=20), range 65-85 years, 6 males, 14 females, were examined. Platelets were counted using a blood analyzer and QTd was measured in standard 12-lead electrocardiograms. Differences in platelet count were assessed by one-way analysis of variance (ANOVA) and the Bonferroni test. Correlation coefficients between platelet count and QTd were calculated with the Spearman rank test. RESULTS: Centenarians showed a lower platelet count compared with controls, which was significant with respect to older controls, group B (p<0.05). QTd values did not significantly differ between centenarians and controls. A significant correlation between QTd and platelet count was evident in centenarians but not in controls. This correlation became evident in control subjects with a platelet count < or = 240,000/mm3. CONCLUSIONS: We hypothesize that a reduced number of platelets and the maintenance of normal QTd may contribute to extreme longevity and protect centenarians from cardiovascular events.     

Metabolic syndrome in aboriginal Canadians: prevalence and genetic associations

OBJECTIVES: The prevalence rates of type 2 diabetes (T2DM) and coronary heart disease (CHD) in Ontario Oji-Cree are among the world's highest. Since metabolic syndrome (MetS) increases risk of T2DM and CHD, we characterized prevalence and putative genetic determinants of MetS in Oji-Cree. METHODS AND RESULTS: In 515 adult (> or = 18 years old) and 115 adolescent (< 18 years old) Oji-Cree subjects, using the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria, we determined that 29.9% of Oji-Cree adults, and 43.4% of adults > or = 35 years of age, had MetS. Furthermore, 33.9 and 8.7% of female Oji-Cree adults and adolescents, respectively, had MetS. Increased waist girth and depressed HDL cholesterol were the most prevalent individual MetS components, while increased blood pressure was least prevalent. AGT T174M, GNB3 825C>T, and APOC3 -455T>C genotypes were significantly associated with MetS (P = 0.018, 0.0056, and 0.029, respectively) for female adults, whereas FABP2 A54T genotype was associated with MetS (P = 0.040) for female adolescents. CONCLUSIONS: The high MetS prevalence in Oji-Cree adults, especially women, is consistent with their high risk of T2DM and CHD. Functional polymorphisms in three candidate genes for plasma lipoproteins and blood pressure were associated with MetS in adult Oji-Cree. Furthermore, several female adolescents met the adult MetS criteria, suggesting that the genesis of MetS begins in youth, especially among aboriginal females.     

Diet quality in association to lipidaemic profile in adults of families at high-risk for type 2 diabetes in Europe: The Feel4Diabetes study

Background and aimsThe role of diet in blood lipids is scarcely investigated in adults at risk of Type 2 Diabetes Mellitus (T2DM) and even less studied regarding their socioeconomic status (SES). This study aimed to investigate the associations of diet quality with blood lipids in adults from families at high-risk for developing T2DM from six European countries, considering their SES.Methods and resultsIn total 2049 adults (67% women) from relatively low-SES regions and high T2DM risk families were enrolled. Dietary habits, sedentary behaviour and sociodemographic characteristics were assessed using standardised questionnaires. The associations of tertiles of healthy diet score (HDS) with blood lipids were tested by univariate analysis of variance (UNIANOVA). HDL-Cholesterol (HDL-C) was positively (B 1.54 95%CI 0.08 to 2.99) and LDL-Cholesterol (LDL-C) (B ?4.15 95%CI ?7.82 to ?0.48), ratio of total cholesterol to HDL-C (B ?0.24 95%CI ?0.37 to ?0.10), ratio of LDL-C to HDL-C (B ?0.18 95%CI ?0.28 to ?0.08) and Atherogenic Index of Plasma (B ?0.03 95%CI ?0.06 to 0.00) inversely associated with the highest tertile of diet score compared to the lowest tertile independently of age, sex, Body Mass Index, total screen time and smoking. In sub-analysis of education (<14 and ≥ 14 years of education), these findings were only significant in the high-SES group.ConclusionWhile diet quality was poorer in the low-SES group, an association between diet quality and lipidemic profile was not found, as increased central obesity and smoking prevalence might have confounded this association. These findings indicate the need for tailor-made interventions, guided by the specific risk factors identified per population sub groups.     

CD28 Expression in T Cell Aging and Human Longevity

Functional decrements of the immune system have a major contribution to aging and age-related diseases. Here, we further characterize the decline in proportion of CD28-positive T cells previously identified in centenarians. Cohorts of 97 centenarians, 40 subjects aged 70–90 (ELD group), and 40 young adults (under age 40) were phenotyped for T cell surface expression of CD28, CD4, and CD8 antigens. The significant decline in T cells expressing CD28 (p < 10⁻⁴ for comparisons between adults and either ELD or centenarians) affects preferentially the CD8⁺ subset of T cells. This decline accounts largely for the age-related diminution of T cell responsiveness to mitogenic signals. CD28 expression is modulated in T cell cultures in a growth-related fashion and this modulation is dampened in cultures from centenarians. We propose that the decrease in CD28 expression reflects a compensatory adaptation of the immune system during aging in the face of chronic stimulation.     

Coronary artery calcification,carotid intima-media thickness and cardiac dysfunction in young adults with type 2 diabetes mellitus

AimsCardiovascular diseases (CVD) are the major causes of mortality in patients with type 2 diabetes mellitus (T2DM). There is paucity of information on prevalence of subclinical atherosclerosis and cardiac dysfunction in young adults with T2DM. This study aimed to assess the prevalence of subclinical atherosclerosis and cardiac dysfunction in young adults with T2DM, asymptomatic for CVD.MethodsSixty-two patients with T2DM, age between 30 and 50 years were evaluated for coronary artery calcium (CAC) score, carotid intima-media thickness (CIMT) and flow-mediated dilatation (FMD) at the brachial artery. All were subjected to 2D-color Doppler echocardiography, electrocardiography and testing for serum N-terminal pro-brain natriuretic peptide (NT-proBNP) and high-sensitivity C-reactive protein (hsCRP). The results were compared with those in 60 age, sex and BMI-matched healthy controls.ResultsPrevalence of a positive CAC score was comparable among subjects with and without T2DM (14.5% vs 11.7%). Patients with T2DM had a significantly higher CIMT (0.54 ± 0.15 vs 0.49 ± 0.10 mm, p = 0.01), left ventricular (LV) mass (170 ± 36 vs 147 ± 23 g, p < 0.001), heart rate (83 ± 13 vs 74 ± 11, p < 0.001) and QTc interval (402 ± 20 vs 382 ± 21 ms, p < 0.001) compared to controls. FMD was lower in patients with T2DM compared to controls (9.1 ± 4.4% vs 10.7 ± 3.9%, p = 0.04). There was a higher prevalence of LV hypertrophy (37% vs 7%, p < 0.001) and diastolic dysfunction (7% vs 0) in patients with T2DM compared to controls. None of the participants had systolic dysfunction. Hypertension (42 vs 7%, p < 0.001) and metabolic syndrome (76 vs 35%, p < 0.001) were more prevalent in the patient group. In the multivariate analysis, age was the lone predictor of CIMT and FMD; while T2DM and male gender were the independent predictors of LV mass.ConclusionsYoung adults with T2DM, asymptomatic for CVD had a higher prevalence of CVD risk factors, LV hypertrophy and diastolic dysfunction. A higher CIMT and LV mass, and a lower FMD were noted in patients with T2DM. CAC score was comparable between the groups and thus may not be a useful tool for assessment of subclinical atherosclerosis in this cohort, where CIMT and FMD may be more appropriate.     

羧基肽酶-H抗体对成人隐匿性自身免疫糖尿病的诊断意义

目的 探讨羧基肽酶—H自身抗体(CPH—Ab)阳性的2型糖尿病(T2DM)患者的临床特征及该抗体对成人隐匿性自身免疫糖尿病(LADA)的诊断价值。方法 选择临床初诊为T2DM患者545例，1型糖尿病(T1DM)患者85例，健康对照123例进行CPH—Ab测定，同时检测T2DM患者谷氨酸脱羧酶抗体(GAD—Ab)。比较各组CPH—Ab的阳性率以及T2DM中依据CPH—Ab、GAD—Ab划分的3组患者的临床特点。采用放射免疫沉淀法检测CPH—Ab和GAD—Ab。结果 CPH—Ab阳性率在T2DM患者(5．5％，30／545)高于T1DM患者(0％，0／85)和正常对照(0．8％，1／123)(P＜0．05)，30例CPH—Ab阳性的T2DM患者只有1例同时GAD—Ab阳性。CPH—Ab在低体重(BMI＜21kg／m^2)者中的阳性率较高，且该抗体阳性的患者具有起病年龄跨度大、病程较长、低体重、易发生酮症等特点，其空腹C肽介于GAD—Ab阳性与两种抗体(GAD—Ab和CPH—Ab)均阴性的T2DM患者之间，反映代谢综合征的指标水平较低(包括较低的BMI、血压和甘油三酯)，而周围神经病变的比例较高。结论 CPH—Ab阳性糖尿病患者的临床特点介于经典的LADA(GAD—Ab阳性)与T2DM患者间。CPH抗体检测是LADA诊断的一项新指标。     

Neuroendocrine features in extreme longevity

In order to evaluate the effects of some neuro-endocrine changes during aging we have studied adrenal, thyroid and pineal secretion in young, healthy old and centenarians. The number of subjects in each hormone group varied. The following parameters were evaluated: serum levels of cortisol, dehydroepiandrosterone-sulfate (DHEAS), free triiodothyronine (FT3), thyroxine (FT4), reverse triiodothyronine (rT3) and thyroid-stimulating hormone (TSH). Urinary 6-hydroxymelatonin sulfate (aMT6s) and free cortisol were measured twice daily. Centenarians exhibited significantly lower TSH levels together with slightly higher rT3 levels than old controls. These changes could be due to reduced 5'-deiodinase activity occurring also in absence of substantial changes of the nutritional pattern. Morning serum cortisol levels were found to be similar in the 3 age groups, whereas the decline of serum DHEAS levels was well evident also after the ninth decade of life. The cortisol/DHEAS molar ratio, which usually increases with age and considered to be an expression of a neurotoxic pattern of the steroidal milieu in the central nervous system, did not shown any further increase in centenarians. The urinary free cortisol and aMT6s excretion declined with age; however only in centenarians and in young controls aMT6s excretion was significantly higher at night than during the day. These findings suggest that the circadian rhythm of melatonin secretion is maintained in centenarians and, based on the limitations of this study, could be considered one factor in successful aging.     

Genetic contribution to circulating levels of hemostatic factors in healthy families with effects of known genetic polymorphisms on heritability

Levels of fibrinogen, factor VII (FVII), factor XIII (FXIII), plasminogen activator inhibitor (PAI)-1, and tissue plasminogen activator have been associated with coronary artery disease as have genetic polymorphisms. Quantitative genetic analyses allow determination of the genetic contribution to phenotypic variation. We investigated familial influences on these hemostatic factors in 537 adults from 89 randomly ascertained healthy families of white North European origin. We used maximum likelihood analysis to estimate the heritabilities of these factors and effects of covariates on the factors in these families. After adjustment for age and sex, the factors showed considerable heritability, varying from 26% (PAI-1) to 47% (FXIII complex). The influence of known polymorphisms was negligible for fibrinogen and contributed 2% to the variance of the FXIII complex and PAI-1 and 11% to the variance of FVII coagulant activity. Age, sex, body mass index, lifestyle, and metabolic covariates explained between 10% (FXIII) and 44% (PAI-1) of phenotypic variance. Childhood household influences significantly affected FVII (11%) and FXIII (18%). A significant degree of phenotypic variance of several hemostatic factors can be explained by additive genes and known covariates. The impact of certain well-characterized polymorphisms to the heritability is small in this population of healthy families, indicating the need to localize new genes influencing hemostatic factor levels.