The Journals of Gerontology Series A Biological Sciences and Medical Sciences

Published by Oxford University Press (OUP)
Online ISSN: 1758-535X
Late-life sexuality is an important quality-of-life issue that has been minimally explored. This survey seeks to extend our knowledge of the relationship of sexual attitudes and preferences to sexual functioning of a large group of older, community-dwelling men. Older men aged 58-94 (N = 1,202) were surveyed with an anonymous self-administered questionnaire including 63 items regarding present and past, actual and desired sexual practices and attitudes. Although age correlated consistently with increased erectile dysfunction and decreased sexual activity, a substantial number of older men continued active sexual behaviors supported by positive attitudes toward sexual function. It was found that both health status and perceived partner's responsiveness are prominent moderators of the age effect. In the absence of social isolation and health issues, many older men show persistently active sexual lifestyles as evidenced in their interest and participation in sexual activities. These findings negate a portion of the starkly negative imagery of sexual expression in aging males.
Distribution profile for both serum vitamin D (25-hydroxyvitamin D [25D] and 1,25-dihydroxyvitamin D [1,25D]) levels among the percentage of men aged 70 and older participating in the Concord Health and Ageing in Men Project (2005–2007), with frailty assigned to different 25D and 1,25D quartiles. A includes the percentage of frail men who have lowest levels of both 25D and 1,25D vitamin D measures. B shows the percentage of frail men with the highest levels of both vitamin D measures.  
Descriptive Characteristics of Men Aged 70 and Older Participating in the CHAMP (2005-2007), With Serum 25D and 1,25D Measures
Logistic Regression Analyses for Associations Between 1,25D Status and Frailty Among the CHAMP Men Before and After Adjustment for Covariates
Background: Poor vitamin D status and frailty are common in older people and associated with adverse health outcomes. The aim of this study was to examine the associations between serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels and frailty and components of frailty in older Australian men. Methods: Cross-sectional analysis of the Concord Health and Ageing in Men Project, a large epidemiological study conducted in Sydney, Australia, between January 2005 and May 2007. Participants included 1,659 community-dwelling men. Main outcome measurements were frailty (assessed using the Cardiovascular Health Study), frailty criteria comprising five core components: weight loss; reduced muscular strength/weakness; slow walking speed; exhaustion; and low activity level, and the separate components of frailty. Covariates included serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels measured by radioimmunoassay, age, country of birth, season of blood collection, sun exposure, body mass index, vitamin D supplement use, income, measures of health, parathyroid hormone, estimated glomerular function. Results: Frailty was present in 9.2% of the sample. Low serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels were independently associated with frailty and with four of the five components of frailty (except weight loss). Conclusions: 1,25-dihydroxyvitamin D and 25-hydroxyvitamin D levels were independently associated with frailty in older men. This suggests that there might be a number of different biological mechanisms for how low vitamin D status might contribute to the frailty syndrome. In addition, the possibility that improving vitamin D status may specifically influence the incidence and progression of frailty needs to be explored.
Distribution of subjects by mild cognitive impairment (MCI) and educational level. Age and Mini-Mental State Examination (MMSE) scores are jittered for better visualization. Open circles: no MCI; filled circles: MCI. The line denotes the cutoff scores. The occasional overflow of open circles below and of solid circles above the cutoff is due to jittering.  
Distribution of Mild Cognitive Impairment by Age and Education Among 1,435 Nondemented Subjects Aged 75 to 95 Years
Sociodemographic and Clinical Features According to Mild Cognitive Impairment (MCI)
Association of Health Indicators With Mild Cognitive Impairment (MCI)
The physical health correlates of mild cognitive impairment (MCI) in the older individual are poorly known. The aim of this study was to investigate the relationship between physical health and MCI with population data. Subjects were 1,435 nondemented 75- to 95-year-old subjects. MCI was defined as scoring one standard deviation below age- and education-specific means on the Mini-Mental State Examination. MCI was consistently associated with indicators of poorer health in logistic regression models with adjustment for potential confounders. The adjusted odds ratios for those with two, three, four, or more somatic symptoms compared with those with one or no symptoms were 1.3 (95% confidence intervals 1.0 to 1.9) and 2.1 (1.2 to 4.5; p for trend =.004); for those with poor self-rated health the odds ratio was 1.9 (1.4 to 2.6); for those with one, two, or more chronic diseases compared with those with no chronic diseases, the odds ratios were 1.3 (0.9 to 1.9) and 3.0 (1.2 to 7.6; p for trend =.02); and for those dying during the 3-year follow-up period the odds ratio was 1.5 (1.1 to 2.2). MCI is associated with poor physical health, leading to the hypothesis of a causal relationship between physical diseases and MCI in older populations.
Prevalence (% of total) of the Main Causes of Disturbed Sleep Onset and Disturbed Sleep Maintenancet 
This epidemiologic study cross-sectionally examined the effects of sex and age on subjective characteristics of sleep and the factors related to self-evaluated sleep quality in a Dutch noninstitutionalized elderly population. 1,692 sleep questionnaires were mailed to all attenders of the general practice serving Krimpen aan de Lek, The Netherlands, aged 50 or over. Both target population and responders (1,485 subjects) were virtually representative of the Dutch population regarding sex and age (50 +) characteristics. Overall, females reported significantly poorer quality of sleep, longer sleep latencies, more nighttime awakenings, less frequent napping, and more frequent use of sedative-hypnotic drugs when compared to males. Additionally, there was a female predominance in the prevalence of disturbed sleep onset and sleep maintenance, whereas a male predominance was observed in the prevalence of excessive daytime sleepiness. Across subjects, a significant age-related increment was found for sleep latency time and time spent in bed. The number of nighttime awakenings increased significantly with age only in males. No significant correlations were found between health status and sex, age, or subjective sleep quality. The most frequently reported causes of disturbed sleep onset and sleep maintenance were worries and nocturia, respectively. Subjective quality of sleep was mostly associated with self-estimated sleep latency. Our findings extend those of previous epidemiologic studies reporting that sleep disorders are common in the general elderly population. Future studies should further elucidate the nature and extent of geriatric sleep disorders to satisfy the increasing need for its accurate diagnosis and treatment.
Body weight, lean body mass (total weight less body fat), carcass protein, and serum protein were examined as potential parameters by which to assess the effect of age on protein requirements for maintenance in male rats, aged 11 months and 18 months, fed diets containing 1.53, 3.41, 4.98, 6.52, or 8.05% dietary protein, casein plus methionine, for a 5-week period. Body weight change was maintained in older animals at 6.52% dietary protein and in younger animals at 4.98% dietary protein. Older animals consuming the two diets highest in protein had a greater percent body fat and less percent body protein than younger animals. Significant effects of diet and the interaction of diet and age on serum protein were also observed. As dietary protein level increased, serum protein increased gradually in younger rats, but only between 3.41 and 4.98% dietary protein in older rats. Lean body mass and total carcass protein increased as dietary protein level increased, but there were no significant differences due to age or the interaction of diet and age. Changes in body weight indicate a greater protein requirement for 18-month-old rats compared with 11 -month-old rats, although complicated by greater food intake and fat deposits in older animals. Measures of body protein indicate that age has some influence on protein needs for maintenance purposes.
Photograph of bulb sensors and external transducer used to measure oral pressure in this study. The ruler (measuring inches) is shown for reference. Downloaded from by guest on 14 May 2020
Example waveform of swallowing pressure versus time for a single bulb, illustrating the method used to determine whether a waveform has single or multiple peaks. This swallow was considered to have two peaks if the ratios, P min /P 1 and P min /P 2 were both less than some value . As the parameter is arbitrary, values of .25, .5, and .75 were examined. Downloaded from by guest on 14 May 2020
The tongue plays a key role in bolus propulsion through the oropharyngeal chamber. In this study, possible age effects on the magnitude and timing of lingual pressure generation were analyzed. Oral pressure was measured during isometric and swallowing tasks for 10 elderly (mean age = 81 years) and 10 young (mean age = 51 years) subjects. Three trials each of the isometric task and swallows of three different boluses (3 ml semisolid, 3 ml liquid, and 10 ml liquid) were performed by each subject. The timing and magnitude of isometric and swallowing pressure generation along with the pattern of the swallowing pressure waveform were analyzed. Whereas maximum lingual isometric pressures decreased with age (p < .001). no significant age difference was found for swallowing pressure. Time taken to reach peak pressure also was reduced with age in both the isometric task and swallows of liquid boluses (p < .05), while no significant age effect was found for semisolid swallows. Finally, only elderly subjects showed a pattern of liquid swallowing pressure generation in which multiple lingual gestures were required to reach peak pressure (termed "pressure building"), a pattern demonstrated by both young and elderly groups for semisolids. Decreased lingual strength with age combined with unchanging swallowing pressure leads to a decreased "pressure reserve," perhaps leaving older individuals more at risk for dysphagia resulting from insults directly or indirectly to the swallowing system. Additionally, swallowing is generally "slowed" with age, apparently due to both central and peripheral factors, and this change may have an impact on bolus flow outcomes.
Values of Bone Mineral Density in the Index Case and Four Relatives 
Osteoporosis is a common disease that affects elderly people. Aging induces loss of bone density and quality resulting in a progressive incidence of fragility fractures. In this study, we report the bone density of one of the oldest men in the world and of several of his first-degree relatives, as well as a genetic screen of these cases. No fractures have been suffered by any of them, and their bone mineral density (BMD) values in terms of z score were normal or lightly decreased. Neither mutations at the longevity-related gene KLOTHO nor the Gly171Val mutation of LRP5 associated with high bone mass was detected in the two centenarian stepbrothers.
We report the prevalence and incidence of cardiovascular disease in older men and women in a long-term health care facility. The prevalence of hypertension, chronic atrial fibrillation, pacemaker rhythm, coronary artery disease (CAD), thromboembolic stroke, and symptomatic peripheral arterial disease (PAD) and the incidence of new coronary events, thromboembolic stroke, and congestive heart failure (CHF) were investigated in 1160 men, mean age 80 +/- 8 years, and in 2464 women, mean age 81 +/- 8 years, in a long-term health care facility. Mean follow-up was 46 +/- 30 months. The prevalences of hypertension, pacemaker rhythm, CAD, and thromboembolic stroke were similar in men and women. The prevalence of atrial fibrillation was higher in men (16%) than in women (13%; p =.019). The prevalence of PAD was higher in men (32%) than in women (26%; p =.0001). At the 46-month follow-up, the incidences of new coronary events, thromboembolic stroke, and CHF were similar in men and women. Older men and women in a long-term health care facility have a high prevalence and incidence of cardiovascular disease. The prevalences of hypertension, pacemaker rhythm, CAD, and thromboembolic stroke and the incidences of new coronary events, thromboembolic stroke, and CHF were similar in men and women. However, the prevalences of atrial fibrillation and of PAD were higher in men than in women.
Phorbol-12,13-dibutyrate (PDBu), an activator of protein kinase C, was used to evaluate potential age-related changes in phosphorylation-dependent facilitation of high-affinity L-glutamate uptake in the rat central nervous system (CNS). Forebrain homogenates from male Fischer-344/brown Norway F1 hybrid rats were separated into glia-enriched (glial plasmalemmal vesicles) and neuron-enriched fractions (synaptosomes) and assayed for sodium-dependent transport of L-[3H]glutamate. Glial fractions from rats aged 5, 25, 31, and 37 months exhibited similar rates of basal L-[3H]glutamate transport and demonstrated no significant age-related differences with respect to the maximal facilitatory effect of PDBu (1–100 μM). In contrast, neuronal fractions exhibited an age-related decline in both indices, with basal L-[3H]glutamate transport decreasing from 710 ± 31 to 560 ± 40 pmoL/mg protein/90 s for the 5- and 37-month groups, respectively (p < .03) and PDBu having a significantly attenuated effect in aged animals. Together, these results provide support for the hypothesis that aging is associated with a decrease in the number of neuronal L-glutamate transporters as well as a diminished capacity to up-regulate these transporters through a protein kinase C–dependent pathway.
We report the incidence of new coronary events and new atherothrombotic brain infarction (ABI) in older men and women with diabetes mellitus, prior myocardial infarction, and a serum low-density lipoprotein (LDL) cholesterol of >/=125 mg/dl treated with statins and with no lipid-lowering drug. The incidence of new coronary events and of new ABI was investigated in an observational prospective study of 529 diabetics, mean age 79 +/- 9 years, with prior myocardial infarction and a serum LDL cholesterol of >/=125 mg/dl treated with statins (279 persons or 53%) and no lipid-lowering drug (250 persons or 47%). Follow-up was 29 +/- 18 months. At follow-up, the stepwise Cox regression model showed that after controlling for other risk factors, the use of statins was associated with a 37% significant independent reduction in the incidence of new coronary events and with a 47% significant independent reduction in the incidence of new ABI. Use of statins was associated with a 37% significant, independent reduction in new coronary events and a 47% significant, independent reduction in new ABI in older men and women with diabetes mellitus, prior myocardial infarction, and a serum LDL cholesterol of >/=125 mg/dl. Elderly diabetics with prior myocardial infarction and increased serum LDL cholesterol should especially be treated with statins.
We report the incidence of new atherothrombotic brain infarction (ABI) in older men and women with prior myocardial infarction and a serum low-density lipoprotein (LDL) cholesterol of >or=125 mg/dl treated with statins and with no lipid-lowering drug. The incidence of new ABI was investigated in an observational prospective study of 1410 men and women, mean age 81 +/- 9 years, with prior myocardial infarction and a serum LDL cholesterol of >or=125 mg/dl treated with statins (679 persons or 48%) and with no lipid-lowering drug (731 persons or 52%). Follow-up was 36 +/- 21 months. At follow-up, the stepwise Cox regression model showed that significant independent predictors of new ABI were age (risk ratio = 1.04 for a 1-year increase in age), cigarette smoking (risk ratio = 3.5), hypertension (risk ratio = 3.1), diabetes mellitus (risk ratio = 2.3), initial serum LDL cholesterol (risk ratio = 1.01 for each 1 mg/dl increase), initial serum high-density lipoprotein cholesterol (risk ratio = 0.97 for each 1 mg/dl increase), prior stroke (risk ratio = 2.5), and use of statins (risk ratio = 0.40). The Cochran-Armitage test showed a trend in the reduction of new ABI in persons treated with statins as the level of serum LDL cholesterol decreased ( p <.0001). Use of statins caused a 60%, significant, independent reduction in new ABI in older men and women with prior myocardial infarction and a serum LDL cholesterol of >or=125 mg/dl.
Combined Occurrence in Percentages (and Numbers of Patients)
Previous studies have indicated that postprandial hypotension (PPH) and orthostatic hypotension (OH) occur infrequently together. As data on geriatric patients in hospitals are scarce, we investigated the prevalence of PPH and OH and their combined occurrence. Our study sample included patients admitted to two geriatric departments in Dutch hospitals. During 9 months, hemodynamic changes were measured with Spacelab 90207 after standing and after meals in all eligible patients. PPH is defined as a meal-related decline in systolic blood pressure (SBP) > or =20 mmHg, OH after standing up. Eighty-five patients (44 men), mean age 80 +/- 7 years (range 60-98 years), with 4 +/- 2 diseases and 6 +/- 3 prescriptions, were included. PPH was present in 57 patients (67%) with a significant postmeal SBP decrease of 34 +/- 4 mmHg. OH was present in 44 patients (52%) with a mean SBP decline of 44 +/- 4 mmHg after standing. Thirty-two patients (37%) had OH and PPH. Only 16 patients (19%) had neither OH nor PPH. Symptoms of PPH were present in 65% of patients, with syncope (in five patients) and sleepiness as the most common symptoms. OH was symptomatic in 61% of patients, with dizziness and risk for falls as the most common symptoms. PPH and OH are more common in geriatric patients than was previously appreciated, with a high statistical probability that OH and PPH occur simultaneously. There is little overlap in symptoms of OH (dizziness, fall risk) versus PPH (sleepiness, syncope), which can play an important role in diagnosis. Because of the high prevalence of symptomatic PPH and OH, blood pressure measurements for diagnosing hypotensive syndromes should be part of a comprehensive geriatric assessment.
Distribution (%) of Other Health and Social Indicators in Men and Women According to Continence Status at Baseline 
Baseline Distribution (%) of Urge Incontinence and Other Health and Social Indicators in Men and Women According to Institutionalization During the 13-Year Follow-Up 
Age-Adjusted and Multivariate Associations of Urge Incontinence and Other Health and Social Indicators with Institutionalization During the 13-Year Follow-Up in Men and Women 
Longitudinal data on predictors of institutionalization in random older populations are limited. The aim here was to identify predictors of institutionalization in an unselected older population during a period of 13 years with a special focus on the prognostic value of urge incontinence. A population-based prospective survey was conducted involving 366 men and 409 women aged 60 years and older. Age-adjusted and multivariate Cox proportional hazards models were used to examine the predictive association of urge incontinence, living arrangements, neurological, cardiovascular, musculoskeletal, and other chronic diseases, activities of daily living (ADL) disability, and depressive symptoms with institutionalization separately in men and women. Adjusted for age, ADL disability and other chronic diseases predicted institutionalization in both men and women. Urge incontinence and depressive symptoms in men and living alone and cardiovascular diseases in women were also significant predictors. In multivariate analyses where all potential predictors were included simultaneously, age (RR [relative risk] 1.15; 95% CI [confidence interval] 1.10-1.19), urge incontinence (RR 3.07; 95% CI 1.24-7.59), and depressive symptoms (RR 1.22; 95% CI 1.00-1.48) remained significant predictors of institutionalization in men. In women, age (RR 1.15; 95% CI 1.12-1.19) and living alone (RR 2.02; 95% CI 1.27-3.21) were independent predictors. In addition to age, urge incontinence and depressive symptoms in men and living alone in women are significant prognostic indicators of institutionalization. The greater prognostic value of urge incontinence in men compared with women emphasizes the importance of interventions aimed at promoting continence and coping with the problem both at the individual and caregiver levels especially among older men.
Standardized health over time. 
Fifty percent confidence intervals for slopes of standardized health. 
Mean Standardized Health Over Time for 13 Measures of Health
Background: The health of older adults declines over time, but there are many ways of measuring health. It is unclear whether all health measures decline at the same rate or whether some aspects of health are less sensitive to aging than others. Methods: We compared the decline in 13 measures of physical, mental, and functional health from the Cardiovascular Health Study: hospitalization, bed days, cognition, extremity strength, feelings about life as a whole, satisfaction with the purpose of life, self-rated health, depression, digit symbol substitution test, grip strength, activities of daily living, instrumental activities of daily living, and gait speed. Each measure was standardized against self-rated health. We compared the 5-year change to see which of the 13 measures declined the fastest and the slowest. Results: The 5-year change in standardized health varied from a decline of 12 points (out of 100) for hospitalization to a decline of 17 points for gait speed. In most comparisons, standardized health from hospitalization and bed days declined the least, whereas health measured by activities of daily living, instrumental activities of daily living, and gait speed declined the most. These rankings were independent of age, sex, mortality patterns, and the method of standardization. Conclusions: All of the health variables declined, on average, with advancing age, but at significantly different rates. Standardized measures of mental health, cognition, quality of life, and hospital utilization did not decline as fast as gait speed, activities of daily living, and instrumental activities of daily living. Public health interventions to address problems with gait speed, activities of daily living, and instrumental activities of daily living may help older adults to remain healthier in all dimensions.
Chondrocyte anabolic activity has been shown to decline with aging, but catabolic activity has received little attention. In this study, the effect of aging on the chondrocyte catabolic response was determined by stimulating isolated human chondrocytes with fibronectin fragments (FN-f) or interleukin-1β and measuring matrix metalloproteinase-13 (MMP-13) production as a catabolic response. A significant age-related increase in chondrocyte MMP-13 production was noted. FN-f stimulation of MMP-13 expression was blocked using a nuclear factor kappa-B (NFκB) inhibitor suggesting a role for NFκB in this chondrocyte catabolic response. Chondrocyte production of the NFκB-regulated cytokine interleukin-1β was also found to increase with donor age in unstimulated cells. These results demonstrate a significant age-related increase in chondrocyte catabolic responsiveness which could contribute to the development of osteoarthritis in older adults.
We have previously reported that men who look older than their contemporaries have a significantly higher risk for myocardial infarction. The purpose of this study was to investigate whether persons with pronounced aging signs such as graying of hair, baldness, or facial wrinkles are prone to a shorter life span compared to their contemporaries. In the Copenhagen City Heart Study comprising a random sample of 20,000 men and women, we also recorded, in addition to cardiovascular risk factors, data on signs of aging: extent of gray hair, baldness, facial wrinkles, and arcus senilis (corneal arcus). During 16 years of follow-up, 3,939 persons (1,656 women and 2,283 men) had died. The Cox regression model for proportional hazards, which included age as an explanatory variable, was used for descriptive analysis of the correlation between these aging signs and all-cause mortality. We found no correlation between the mortality and the extent of graying of the hair, or baldness or facial wrinkles in either of the sexes, irrespective of age. A single exception was observed in a small subgroup of men with no gray hair. They had a slightly, but significantly, lower mortality than the rest [relative risk (RR) = .81, 95% confidence interval (CI) .67-.98; p < .05]. The presence of arcus senilis was significantly correlated with a shorter life span in women (RR = 1.25, 95% CI 1.08-1.46; p < .01). For men the same tendency was found, but the correlation was not statistically significant. We conclude that the degrees of graying of the hair, baldness, and facial wrinkles are not predictive of a shorter life span in men and women in the Copenhagen City Heart Study.
The potential influence of cognitive status, physical activities, comorbidity and cotreatments on the feasibility and diagnostic accuracy of two noninvasive diagnostic tests for Helicobacter pylori (Hp) infection, i.e., the 13C-urea breath test (13C-UBT) and serology (immunoglobulin G [IgG] anti-Hp antibodies), in older subjects is not known. The study involved 100 consecutive symptomatic elderly subjects (mean age, 78.3 years; range, 65-96 years), who had undergone an upper gastrointestinal endoscopy. Patients were considered Hp positive if at least two of the three invasive methods, i.e. histology, culture, and/or the rapid urease test were positive for Hp infection. Patients were considered Hp negative if all three invasive methods were negative. The 13C-UBT was performed according to the European standard method and the assaying of IgG anti-Hp antibodies by enzyme-linked immunosorbent assay. Cognitive status and functional activities were determined by the Mini-Mental State Examination (MMSE), the activities of daily living (ADLs) and instrumental ADLs (IADLs). According to invasive methods, 49 patients were Hp positive and 47 were Hp negative (4 subjects were excluded from the study). Hp-positive patients demonstrated a significantly higher prevalence of peptic ulcers (p =.02) and activity of chronic gastritis (p<.0001) than Hp-negative subjects. The 13C-UBT demonstrated a sensitivity of 100%, a specificity of 95.7%, and a diagnostic accuracy of 97.9%. Serology had significantly lower sensitivity (74.4%), specificity (59%), and diagnostic accuracy (67%, p<.001) than the 13C-UBT. The feasibility and the diagnostic accuracy of the 13C-UBT were not altered by the cognitive status (MMSE) and functional activities (ADL, IADL) of the patients, their drug consumption, or the prevalence of concomitant diseases. In older subjects, the 13C-UBT had a significantly higher diagnostic accuracy than serology without influence of cognitive function, disability, comorbidity and cotreatments. This method may be considered an excellent, clinically useful, noninvasive test for the diagnosis of Hp infection in older subjects.
Trajectories of BMI by s moking s tatus, 1992 – 2006. Based on M3 with statistically signifi cant time interactions ( Table 4 ) .  
Trajectories of BMI by a lcohol u se s tatus, 1992 – 2006. Based on M3, nonsignifi cant time interactions for alcohol use and physical activity excluded ( Table 4 ).  
Trajectories of BMI by p hysical a ctivity s tatus, 1992 – 2006. Based on M3, nonsignifi cant time interactions for alcohol use and physical activity excluded ( Table 4 ).  
Sample Baseline Characteristics and Attrition Status Indicators * ( N = 10,314 respondents)
Trajectories of BMI by c hange in s moking and by PA s tatus, 1992 – 2006. Based on M3 with statistically signifi cant time interactions ( Table 4 ).  
Obesity is increasingly prevalent among older adults, yet little is known about the impact of health behaviors on the trajectories of body weight in this age group. We examined the effect of time-varying smoking, physical activity (PA), alcohol use, and changes thereof, on the 14-year (1992-2006) trajectory of body- mass index (BMI) in a cohort of 10,314 older adults from the Health and Retirements Study, aged 51-61 years at baseline. Hierarchical linear modeling (HLM) quantifies the effect of smoking, PA, and alcohol use (user status, initiation and cessation) on intercept and rate-of-change in BMI trajectory, and tests for variations in the strength of association between each behavior and BMI. Over 14 years (82,512 observations), BMI increased approximated by a quadratic function. Smoking and PA (user status and initiation) were associated with significantly lower BMI trajectories over time. Cessation of smoking and PA resulted in higher BMI trajectories over time. The weight-gaining effect of smoking cessation increased, while the strength of association between BMI trajectories and PA or alcohol use were constant over time. Socio-economic and health status differences explained the effects of alcohol use on BMI trajectory. In older adults, smoking and PA, and changes thereof, vary in their long-term effect on trajectories of BMI. Barring increases in PA levels, older smokers who quit today are expected to gain significantly more weight than two decades ago. This knowledge is essential for the design of smoking cessation, physical activityPA, and weight-control interventions in older adults.
The dependence of 15 N AIR (d15N ordinate) upon the reported frequency of eating beans (abscissa) in the controls () and Alzheimer's disease (AD) patients (*). Frequency of eating defined as 0 never; 1 rarely; 2 once a week; 3 two or three times per week; 4 every day. As expected, 15 N AIR related inversely to frequency of eating beans in both groups. Unexpectedly, the inverse relation was steeper in AD patients than controls.  
The relations between homocysteine (ordinate) and 15 N AIR (d15N abscissa) in the controls () and Alzheimer's disease (AD) patients (*). Homocysteine levels related inversely to 15 N AIR in controls, but not in patients.  
The relation between CAMCOG scores (ordinate) and 15 N AIR in hair (abscissa) in the controls () and Alzheimer's disease (AD) patients (*). AD patients with higher 15 N AIR (reflecting greater consumption of fish and/or lower consumption of beans) had higher CAMCOG scores.  
Previous researchers have suggested that a vegetarian diet or one rich in fish may protect against Alzheimer's disease (AD). However, assessing diet is difficult in AD patients. (15)N:(14)N isotopic ratios (delta(15)N) of body proteins can estimate long-term dietary habits in a way that does not depend on memory. delta(15)N is high in people who eat a lot of fish and low in vegetarians. To choose between the vegetarian and fish hypotheses of AD, we compared dietary questionnaire reports and delta(15)N of hair samples from AD patients and controls. Patients' cognitive scores related directly to reported frequency of eating fish and to hair delta(15)N(AIR), but inversely to reported frequency of eating beans. Homocysteine levels related inversely to hair delta(15)N(AIR) in controls, but not in patients. Dietary questionnaire reports accounted for slightly more variance in delta(15)N(AIR) in patients than controls. Therefore, our questionnaire assessed dietary habits as reliably for individuals with AD as for cognitively unimpaired controls. A diet rich in fish may ameliorate AD, possibly by lowering homocysteine, but more vegetarian diets do not. In fact, eating beans correlated with worse cognition in AD patients. Further studies should test if restricting the intake of beans slows the progression of AD.
Mean exercise over time. Exercisers maintained high levels of exercise throughout the 16 years, whereas Sedentary remained relatively inactive. On average, Increasers achieved greater than a 6-fold increase in exercise min/ wk, whereas Decreasers experienced a greater than 8-fold decrease. 
Participant Characteristics at Baseline and End of Study 
Mean disability over time. At baseline, all groups had very low levels of disability. The Sedentary group experienced the poorest end-of-study Health Assessment Questionnaire Disability Index (HAQ-DI) score, increasing 0.37 to 0.42. Exercisers achieved the best end-of-study HAQ-DI score, increasing only 0.11 to 0.14. Increasers achieved good end-of-study HAQ-DI score, increasing 0.17 to 0.20. Decreasers experienced poor end-of-study HAQ-DI score, increasing 0.28 to 0.36. 
Changes in Participant Characteristics From Baseline 
HAQ-DI Score (Standard Error) at Baseline, End of Study, and Change Over Time 
The effect of changes in physical exercise on progression of musculoskeletal disability in seniors has rarely been studied. We studied a prospective cohort annually from 1984 to 2000 using the Health Assessment Questionnaire Disability Index (HAQ-DI). The cohort included 549 participants, 73% men, with average end-of-study age of 74 years. At baseline and at the end of the study, participants were classified as "High" or "Low" vigorous exercisers using a cut-point of 60 min/wk. Four groups were formed: "Sedentary" (Low-->Low; N = 71), "Exercise Increasers" (Low-->High; N = 27), "Exercise Decreasers" (High-->Low; N = 73), and "Exercisers" (High-->High; N = 378). The primary dependent variable was change in HAQ-DI score (scored 0-3) from 1984 to 2000. Multivariate statistical adjustments using analysis of covariance included age, gender, and changes in three risk factors, body mass index, smoking status, and number of comorbid conditions. Participants also prospectively provided reasons for exercise changes. At baseline, Sedentary and Increasers averaged little exercise (16 and 22 exercise min/wk), whereas Exercisers and Decreasers averaged over 10 times more (285 and 212 exercise min/wk; p <.001). All groups had low initial HAQ-DI scores, ranging from 0.03 to 0.08. Increasers and Exercisers achieved the smallest increments in HAQ-DI score (0.17 and 0.11) over 16 years, whereas Decreasers and Sedentary fared more poorly (increments 0.27 and 0.37). Changes in HAQ-DI score for Increasers compared to Sedentary were significantly more favorable (p <.05) even after multivariate statistical adjustment. Inactive participants who increased exercise achieved excellent end-of-study values with increments in disability similar to those participants who were more active throughout. These results suggest a beneficial effect of exercise, even when begun later in life, on postponement of disability.
Stabilization of the hypoxia-inducible factor (HIF-1) protein extends longevity in Caenorhabditis elegans. However, stabilization of mammalian HIF-1α has been implicated in tumor growth and cancer development. Consequently, for the hypoxic response to benefit mammalian health, we must determine the components of the response that contribute to longevity, and separate them from those that cause harm in mammals. Here, we subject adult worms to low oxygen environments. We find that growth in hypoxia increases longevity in wild-type worms but not in animals lacking HIF-1 or DAF-16. Conversely, hypoxia shortens life span in combination with overexpression of the antioxidant stress response protein SKN-1. When combined with mutations in other longevity pathways or dietary restriction, hypoxia extends life span but to varying extents. Collectively, our results show that hypoxia modulates longevity in a complex manner, likely involving components in addition to HIF-1.
Inhibition of either the insulin-like or target of rapamycin (TOR) pathways in the nematode Caenorhabditis elegans extends life span. Here, we demonstrate that starvation and inhibition of the C. elegans insulin receptor homolog (daf-2) elicits a daf-16-dependent up-regulation of a mitochondrial superoxide dismutase (sod-3). We also find that although heat and oxidative stress result in nuclear localization of the DAF-16 protein, these stressors do not activate a SOD-3 reporter, suggesting that nuclear localization alone may not be sufficient for transcriptional activation of DAF-16. We show that inhibition of either TOR activity or key components of the cognate translational machinery (eIF-4G and EIF-2B homologs) increases life span by both daf-16-dependent and -independent mechanisms. Finally, we demonstrate that at least one nematode hexokinase is localized to the mitochondria. We propose that the increased life spans conferred by alterations in both the TOR and insulin-like pathways function by inappropriately activating food-deprivation pathways.
The level of green fluorescent protein expression from an hsp-16.2-based transcriptional reporter predicts life span and thermotolerance in Caenorhabditis elegans. The initial report used a high-copy number reporter integrated into chromosome IV. There was concern that the life-span prediction power of this reporter was not attributable solely to hsp-16.2 output. Specifically, prediction power could stem from disruption of some critical piece of chromatin on chromosome IV by the gpIs1 insertion, a linked mutation from the process used to create the reporter, or from an artifact of transgene regulation (multicopy transgenes are subject to regulation by C elegans chromatin surveillance machinery). Here we determine if the ability to predict life span and thermotolerance is specific to the gpIs1 insertion or a general property of hsp-16.2-based reporters. New single-copy hsp-16.2-based reporters predict life span and thermotolerance. We conclude that prediction power of hsp-16.2-based transcriptional reporters is not an artifact of any specific transgene configuration or chromatin surveillance mechanism.
One of the most pervasive ideas regarding the causes of aging is that longevity is constrained in large measure by damage to macromolecules. An increasing body of cellular and molecular data, generated over the past decade or so, has generally supported this “damage accumulation” hypothesis of aging. There remain unanswered questions regarding which types of damage are most important for driving aging. In addition, there have been recent challenges to the damage accumulation hypothesis and a new emphasis on the importance of cellular responses and the sequelae to damage, rather damage per se. New tools and approaches are on the horizon and will need to be developed and implemented before we can fully understand whether and to what extent macromolecular damage drives aging phenotypes.
Levels of 17b-estradiol of vehicle (V ¼ n)-treated and estradiol (E ¼ h)-treated rats at 0, 6, 12, 18, and 24 months of age. Mean 6 standard error of the mean for 7 animals. Significant differences are shown. * ¼ V versus E; § ¼ month versus next month. 
Comparison of body weight of vehicle (V ¼ n)-treated and estradiol (E ¼ h)-treated rats. Mean 6 standard error of the mean for 7 animals. Significant differences are shown. * ¼ V versus E; § ¼ month versus next month. 
Mean latencies (6 standard error of the mean) to locate the platform across training days in the water maze for the experimental groups. Comparisons between vehicle (V ¼ n)-treated and estradiol (E ¼ h)-treated rats were not significant in any of the four treatment groups analyzed (A, 0 months; B, 6 months; C, 12 months; D, 18 months; n ¼ 7 per group). Only V and E groups at 0 months showed a significant decrease in escape latencies with training days ( p , .01). 
Probe trial performance as assessed by the percent time spent in the quadrant that previously contained the escape platform. *p , .05 versus groups treated at 6, 12, and 18 months of age with vehicle (V ¼ n) or estradiol (E ¼ h). 
Blood glucose concentrations (A-E) and glucose infusion rate (F-J) during euglycemic clamp experiments. Data shown for experimental months 0 (A and F), 6 (B and G), 12 (C and H), 18 (D and I), and 24 (E and J). Values shown for vehicle (V ¼ n)-treated and estradiol (E ¼ h)-treated rats. Significant differences are shown. Comparisons between mean values from 40 to 60 minutes during euglycemic-hyperinsulinemic clamp experiments were evaluated. Mean 6 standard error of the mean for 7 animals. * ¼ V versus E. 
Aging is associated with insulin resistance, which represents a common factor in age-related diseases. We aimed to determine the role of 17beta-estradiol on insulin sensitivity and memory during aging using ovariectomized rats (2-26 months of age) treated with physiological doses of 17beta-estradiol. Our results indicate a lack of effect of 17beta-estradiol replacement on spatial memory assessed in a water maze. Conversely, estradiol treatment improved insulin sensitivity in aging rats. These data imply that relatively low doses of 17beta-estradiol may have beneficial effects on glucose homeostasis due to the protective effects of estrogen. However, estradiol treatment used in the present study did not prevent memory impairment associated with aging.
Baseline Characteristics* 
Baseline Values for Markers on Inflammation and Vascular Reactivity in Older Women 
Baseline Lipoprotein Lipid Values for Older Women on Estrogen 
Point Estimates of the Difference in Percent Change in Selected Cardiovascular Risk Factors With Micronized Estradiol Treatment Compared with Placebo at 12 Weeks on Treatment and 12 weeks Post-Treatment in Older Women 
The authors evaluated the effect of 3 doses (0.25 mg/day, 0.5 mg/day, and 1 mg/day) of micronized 17beta-estradiol (E2) on C-reactive protein (CRP), interleukin-6 (IL-6), and lipids, compared with placebo, in healthy older women participating in an osteoporosis study. This randomized, double-blind, placebo-controlled study was conducted in a University clinical research center. Participants were healthy, community-living women older than 65 years. The primary outcome measure of the study was bone metabolism as estimated by serum and urine markers of bone turnover. For this analysis, the authors measured serum markers of CRP, IL-6, lipids, intracellular adhesion molecule-1, and E-selectin at baseline, after 12 weeks of treatment, and after 12 weeks with no treatment. A significant dose-response effect of estrogen occurred on CRP levels. After 12 weeks of treatment, CRP decreased 59% in the 0.25 mg/day E2 group and increased 65% in the 1 mg/day E2 group, compared with placebo. The CRP level continued to be elevated (92%), compared with placebo, 12 weeks after treatment was discontinued in the 1 mg/day E2 group. High-density lipoprotein (HDL) and HDL2 cholesterol increased and low-density lipoprotein (LDL) cholesterol decreased at 12 weeks in the 1 mg/day E2 group, with a significant dose-response effect. E-selectin decreased significantly in the 1 mg/day E2 group 12 weeks after discontinuation of treatment (-7%), and there was a significant dose-response effect at this time. The 2 lower doses did not affect any of these parameters. Total and HDL3 cholesterol, triglycerides, lipoprotein(a), intracellular adhesion molecule-1, and IL-6 did not change with any dose of E2. C-reactive protein, an inflammation marker associated with increased risk for cardiovascular disease, decreased in women taking the lowest estrogen dose but increased in women assigned to the highest estrogen dose, suggesting decreased inflammation with lower dose E2. However, with 3 months of treatment, 0.25 or 0.5 mg/day E2 did not have the same beneficial effects on HDL or LDL cholesterol as did 1 mg/day E2. These data suggest that estradiol doses have differential short-term effects on markers of cardiovascular disease. Low-dose E2 decreased CRP, an important marker of inflammation, but did not affect lipid parameters, whereas the highest dose increased CRP and had a beneficial effect on lipid parameters. The long-term consequences of these effects are unknown, but it is possible that estradiol dose should be considered when risk:benefit ratios are evaluated for individual women before estrogen replacement therapy is initiated.
Interleukin-15 (IL-15) and interleukin-18 (IL-18) are potential regulators of body composition in humans. The authors previously reported that megestrol acetate ingestion causes a large accumulation of adipose tissue and reduces muscle mass. Therefore, the purpose of this investigation was to evaluate the effects of megestrol acetate ingestion on circulating IL-15 and IL-18 concentrations in healthy elderly men. All participants received 800 mg of megestrol acetate per day during this 12-week study. Megestrol acetate was combined with testosterone injections (100 mg/week), placebo injections, resistance training, or resistance training and testosterone. Resting IL-15 and IL-18 concentrations were measured by enzyme-linked immunosorbent assay at week 0 (pre), week 6 (mid), and week 12 (post). The time effect for IL-15 was significant (p = .0008), with the mid and post values being significantly greater than the pre value. The change in IL-15 concentration was not significantly related to the change in muscle mass (r = -.31; p > .05), nor was it related to the change in fat mass (r =.17; p > .05). Differences among groups or over time were not significant for IL-18, nor were correlations between pre body weight and pre IL-18 (r = -.03), pre fat mass and pre IL-18 (r = .14), or the change in fat mass and the change in IL-18 (r = -.07). IL-15 was increased as a result of megestrol acetate ingestion; however, megestrol acetate did not affect circulating IL-18 concentrations, and the change in IL-18 did not correlate with any body composition variables.
Racial and gender differences in mortality rates have been reported for patients with systolic heart failure. Relatively little is known regarding diastolic heart failure prognosis. Our sample consisted of 1058 patients 65 years of age or older who were admitted to 30 hospitals in Northeastern Ohio with a principal diagnosis of heart failure and a left ventricular ejection fraction of >/=50% by echocardiogram. Of the 1058 patients with diastolic heart failure (13% African American and 87% white), African Americans and whites were comparable with respect to history of angina, stroke, being on dialysis, and alcohol use; the proportion of male patients was also comparable. The African American to white adjusted odds ratio for 18-month mortality (all cause) was 1.03 (0.66-1.59). For men versus women (30% vs 70%), the above-mentioned comorbidities were comparable, except women were more likely to have a do not resuscitate status (16% vs 7.3%; p =.000) and to be older (79.5 +/- 8 vs 77 +/- 7; p =.000). Men were more likely to have a history of tobacco use (30% vs 14%; p =.000) and alcohol use (36% vs 15%; p =.000), and a higher serum creatinine level (1.7 +/- 1.2 vs 1.4 +/- 1.1; p =.001). The men to women adjusted odds ratio for 18-month mortality (all cause) was 1.06 (0.76-1.46). In this cohort of elderly patients admitted with diastolic heart failure, there were no ethnic or gender differences in 18-month mortality rates.
Forest plot for the association of the IL-18 rs5744256 single nucleotide polymorphism and physical function, meta-analysis of new and previously published data. Notes: Effect estimates are based on the inverse transformed standardized times and provide the regression coeffi cient per C allele. ELSA = English Longitudinal Study of Ageing; Iowa-EPESE = Iowa-Established Populations for Epidemiological Study of the Elderly. 
Association of the IL-18 rs5744256 Single Nucleotide Polymorphism With Walking Times, Results from Replication Analysis 
Levels of the proinflammatory cytokine interleukin-18 (IL-18) are raised in old age and are associated with reduced physical functioning. Previous studies have indicated that the C allele of the rs5744256 polymorphism in the IL-18 gene is strongly associated with reduced circulating IL-18 levels. This variant has previously been associated with improved locomotor performance in old age, but the finding requires independent replication. We examined the association between the IL-18 polymorphism rs5744256 and physical functioning in three cohorts with a total of 4,107 participants aged 60-85 years: the English Longitudinal Study of Ageing, Caerphilly, and Boyd Orr. We meta-analyzed (N = 6,141) the results with data from the original paper reporting this association: Iowa-Established Populations for Epidemiological Study of the Elderly and InCHIANTI cohorts. Physical functioning was assessed by timed walks or the get up and go test. As locomotor performance tests differed between the cohorts and the distributions of times to complete the test (in seconds) were positively skewed, we used the reciprocal transformation and computed study-specific z scores. Based on the three new studies, the estimated linear regression coefficient per C allele was 0.011 (95% confidence interval [95% CI]: -0.04 to 0.06). A meta-analysis that pooled the data from all studies showed weak evidence of an effect, with a regression coefficient of 0.047 (95% CI: 0.010 to 0.083). We did not replicate an association between the IL-18 rs5744256 polymorphism and the physical function in people aged 60-85 years. However, pooling data from all studies suggested a weak association of the C allele of the rs5744256 single nucleotide polymorphism on improving walking times in old age.
Associations of IL-18 Serum Levels (Log Transformed) With Measures of Function in the InCHIANTI Study (Ages 65-80 Years)
The proinflammatory cytokine interleukin-18 (IL-18) is associated with major disabling conditions, although whether as byproduct or driver is unclear. The role of common variation in the IL-18 gene on serum concentrations and functioning in old age is unknown. We used 1671 participants aged 65-80 years from two studies: the InCHIANTI study and wave 6 of the Iowa-Established Populations for Epidemiological Study of the Elderly (EPESE). We tested three common polymorphisms against IL-18 concentration and measures of functioning. In the InCHIANTI study, a 1 standard deviation increase in serum IL-18 concentrations was associated with an increased chance of being in the 20% of slowest walkers (odds ratio 1.45; 95% confidence interval, 1.17-1.80; p =.0007) and 20% of those with poorest function based on the Short Physical Performance Battery Score (odds ratio 1.52; 95% confidence interval, 1.22-1.89; p =.00016) in age sex adjusted logistic regression models. There was no association with Activities of Daily Living (p =.26) or Mini-Mental State Examination score (p =.66). The C allele of the IL-18 polymorphism rs5744256 reduced serum concentrations of IL-18 by 39 pmol/mL per allele (p =.00001). The rs5744256 single nucleotide polymorphism was also associated with shorter walk times in InCHIANTI (n = 662, p =.016) and Iowa-EPESE (n = 995, p =.026). In pooled ranked models rs5744256 was also associated with higher SPPB scores (n = 1671, p =.019). Instead of adjusting for confounders in the IL-18 walk time association, we used rs5744256 in a Mendelian randomization analysis: The association remained in instrumental variable models (p =.021). IL-18 concentrations are associated with physical function in 65- to 80-year-olds. A polymorphism in the IL-18 gene alters IL-18 concentrations and is associated with an improvement in walk speed. IL-18 may play an active role in age-related functional impairment, but these findings need independent replication.
In animal studies, caloric restriction resulting in increased longevity is associated with a reduction in body temperature, which is strain specific and likely under genetic control. Small studies in humans have suggested that temperatures may be lower among elderly populations, usually attributed to loss of thermoregulation. We analyzed cross-sectional data from 18,630 white adults aged 20-98 years (mean 58.3 years) who underwent oral temperature measurement as part of a standardized health appraisal at a large U.S. health maintenance organization. Overall, women had higher mean temperatures (97.5 ± 1.2°F) than men (97.2 ± 1.1°F; p < .0001). Mean temperature decreased with age, with a difference of 0.3°F between oldest and youngest groups after controlling for sex, body mass index, and white blood cell count. The results are consistent with low body temperature as a biomarker for longevity. Prospective studies are needed to confirm whether this represents a survival advantage associated with lifetime low steady state temperature.
Oral anticoagulant (OA) therapy is widely used in elderly patients because of the increase of indications with age (venous thromboembolism and atrial fibrillation). A particularity of France is to administer three different OAs (warfarin and more often fluindione or acenocoumarol). In an attempt to assess the particularities of managing all three OAs in elderly patients in clinical practice, we studied the modalities of anticoagulation of 187 consecutive OA therapy patients (mean age = 74.4 years) hospitalized in an Internal Medicine department (95 patients on OA at admission and 92 patients initiated on OA during hospitalization). Patients aged 75 years or older more often required a low dosage of OA than those aged younger than 75, irrespective of the OA (warfarin and more often fluindione or acenocoumarol). Ambulatory patients aged 75 years or older were more susceptible to receive acenocoumarol than were ambulatory patients younger than 75 years (respectively 30/67 vs 8/28, respectively), whereas fluindione was prescribed at the same frequency in ambulatory patients and hospitalized patients, regardless of age group (> or =75: 32/67; <75: 19/28). In hospitalized patients with OA induction, fluindione was prescribed as often in patients younger than 75 than in patients aged 75 years or older (40/47 vs 35/45, respectively). On admission, international normalized ratio was in the target range in 26 of the 95 patients (27.4%) and was >3 in 51 of the 95 patients (51.6%). OA therapy was stopped during hospitalization in 35 patients (36.8%). In conclusion, we have a picture of the practice of anticoagulation with three different OA therapies. Although it is usually recommended to prescribe long half-time OA therapy (2), it appears that short half-time therapy such as acenocoumarol still represents an important number of OA prescriptions in France, especially in ambulatory and elderly patients. International normalized ratio is not in the target range as often as expected in clinical practice, and elderly patients require specific modalities of OA therapy management, such as half dose initiation, use of long-half-life OA, and close monitoring.
Cross-sectional association of body weight in the 5 years prior to death according to age at measurement and birth cohort. 
Estimated body weight in the 5 years prior to death according to age at measurement and birth cohort.
Association Between Birth Cohort and Body Weight at Last Visit Among Men Aged 60 -90 Years
The prevalence of overweight and obesity has increased in all age groups, including older adults. However, it is not known whether higher body weight is maintained in the very old and in the years prior to death. The present study examines whether there are secular trends in body weight in old age among three birth cohorts. The study population includes 1,364 Caucasian men born between 1877 and 1941 from the Baltimore Longitudinal Study of Aging who were followed until death. Four hundred and seventy-seven men had body weight measured during the last 5 years prior to death. Body weight was measured biannually with the last visit occurring between 1959 and 2008. Differences in body weight at the last visit and body weight trajectories across birth cohorts were examined with linear regression and linear mixed-effect regression models. Men born between 1920 and 1941 had significantly higher body weight over the entire follow-up time compared with men born between 1900 and 1919 (p < .001) and 1877 and 1899 (p = .001), and the difference was also significant between the two earlier birth cohorts (p < .001). A significant increasing trend in body weight across birth cohorts was also observed in the few years prior to death. In generally healthy men, there is a significant secular increase in body weight over the adult life span and in the few years prior to death. This study confirms that the obesity epidemic also extends into late life in the current elderly population.
The number of centenarians has increased rapidly since the 1950s. In Denmark, 42% more of the 1905 birth cohort made it to 100 years of age compared to the 1895 cohort. We tested whether this increased survival proportion has resulted in an increased disability level in the more recent cohort of centenarians. The Longitudinal Study of Danish Centenarians (LSDC) included all persons who reached the age of 100 years in the period from April 1, 1995 through May 31, 1996 (a total of 276 persons). In total, 207 persons participated in the survey (75%). The Danish 1905 Cohort Survey included all individuals born in Denmark in 1905. At baseline in 1998, a total of 2262 persons participated in the intake survey (63%). In total, 225 of 364 persons (62%) who reached their 100th birthday in the cohort participated in the most recent 2005 wave. Basic Activities of Daily Living (BADLs) and Physical Activities of Daily Living (PADLs) were assessed in both cohorts. The 1905 cohort displayed better self-reported ADLs than the 1895 cohort did. Stratified by gender, this apparent cohort advantage was due to women in the 1905 cohort performing significantly better than their female counterparts in the 1895 cohort. The increasing number of female centenarians does not entail increasing proportions of disabled individuals. In contrast, there is a lack of improvement in ADLs among male centenarians even though the number of male centenarians is stagnating.
Thirty cross-trained, female subjects (19-69 years) completed an endurance exercise session (ES), a resistance exercise session (RS), and a control session (CS) in a randomized, balanced design. The ES consisted of 40 minutes of cycling at 75% maximum heart rate, and the RS consisted of 3 sets of 10 repetitions of eight exercises. During the CS, subjects performed no exercise. Before and after exercise, and after 30 minutes of recovery, blood samples were analyzed for plasma lactate and serum growth hormone, insulin-like growth factor 1, testosterone, estradiol, dehydroepiandrosterone, and cortisol. Samples were taken during the CS at the same intervals as during the exercise sessions. There were no age-related differences in intensity measures during exercise. Absolute change from baseline in testosterone (p <.001), estradiol (p <.05), and growth hormone (p <.01) was significantly greater in the ES and RS compared with that in the CS. Absolute change in dehydroepiandrosterone was significantly greater in the RS only (p <.05). Results indicate that an acute bout of exercise can increase concentrations of anabolic hormones in females across a wide age range.
We previously demonstrated a significant association of the interleukin-10 (IL-10) −819 T/C polymorphism with age. IL-19 stimulates the production of IL-10, and the IL-19 gene is located adjacent to the telomere side of the IL-10 gene. To explore the relationship between IL-19 single nucleotide polymorphisms (SNPs) and age, we genotyped 500 Japanese individuals (mean age: 56.7 years, range 19–100) for IL-19 Ser175Phe (T/C), −513 T/C, 1098 G/T (intron 1) and 5420 G/C (5′-untranslated region). Three of four SNPs (Ser175Phe, −513 T/C and 1098 G/T) exhibited a weak but significant association with age by chi-square test and logistic regression analysis (p <.05). IL-19 Ser175Phe was in linkage disequilibrium with −513 T/C and 1098 G/T, but not with IL-10 −819 T/C. These data suggest that IL-19 polymorphisms may be associated with age in a Japanese population.
Cancer Incidence in Danish Same-Sex Twins Born in 1900-1918 and Stratified for Age at Death of Cotwin; Analyses of Subpopulations of One Randomly Selected Twin From Each Twin Pair 
Cancer Incidence in Danish Same-Sex Twins With Known Zygosity Born 1900-1918 Stratified for Age at Death of Cotwin 
Animal models and a few human studies have suggested a complex interaction between cancer risk and longevity indicating a trade-off where low cancer risk is associated with accelerating aging phenotypes and, vice versa, that longevity potential comes with the cost of increased cancer risk. This hypothesis predicts that longevity in one twin is associated with increased cancer risk in the cotwin. A total of 4,354 twin pairs born 1900-1918 in Denmark were followed for mortality in the Danish Civil Registration System through 2008 and for cancer incidence in the period 1943-2008 through the Danish Cancer Registry. The 8,139 twins who provided risk time for cancer occurrence entered the study between ages 24 and 43 (mean 33 years), and each participant was followed up to death, emigration, or at least 90 years of age. The total follow-up time was 353,410 person-years and, 2,524 cancers were diagnosed. A negative association between age at death of a twin and cancer incidence in the cotwin was found in the overall analyses as well as in the subanalysis stratified on sex, zygosity, and random selection of one twin from each twin pair. This study did not find evidence of a cancer-longevity trade-off in humans. On the contrary, it suggested that longevity in one twin is associated with lower cancer incidence in the cotwin, indicating familial factors associated with both low cancer occurrence and longevity.
Number (%) of Reported Physical Limitations, Socioeconomic Position (SEP; childhood and adult), and Educational Achievement at Ages 43 and 53 Years, by Gender 
Prevalence (95% confidence interval) of upper and lower body functional limitations at ages 43 and 53 years by gender (men = 1,530, women = 1,518). 
Prevalence (95% confidence interval) of lower body functional limitations at ages 43 and 53 years for combinations of manual (M) compared with non-manual (NM) occupational social class during childhood (CSEP) and adulthood (ASEP) by gender (men = 1,530, women = 1,518). Calculated from model that included CSEP, ASEP, age, CSEP × Age interaction (Table 2, Model 2). 
Prevalence (95% confidence interval) of upper body functional limitations at ages 43 and 53 years for combinations of manual (M) compared with non-manual (NM) occupational social class during childhood (CSEP) and adulthood (ASEP) by gender (men = 1,530, women = 1,518). Calculated from model that included CSEP, ASEP, age, CSEP × Age interaction (Table 2, Model 2). 
Older women and those of lower socioeconomic position (SEP) consistently constitute a larger portion of the disabled population than older men or those of higher SEP, yet no studies have examined when in the life course these differences emerge. Prevalence of self-reported limitations in the upper body (gripping or reaching) and lower body (walking or stair climbing) at 43 and 53 years were utilized from 1,530 men and 1,518 women from the British 1946 birth cohort. Generalized linear models with a binomial distribution were used to examine the effects of gender, childhood and adult SEP, and the differences in the SEP effects by gender on the prevalence of limitations at age 43 years and changes in prevalence from 43 to 53 years. For both genders, the prevalence of upper and lower body limitations were reported at 3%-5% at age 43 years. However, by age 53 years, women's upper body limitations had increased to 28% and lower body limitations to 21%, whereas men's limitations had only increased to 12% and 11%, respectively. Men and women whose father's occupation was manual or whose adult head of household occupation was manual had higher prevalence of both limitations compared with those with non-manual backgrounds. These differences widened with age, especially in women. The effect of adult SEP on the prevalence of limitations was stronger than that of childhood SEP and was partly mediated by educational attainment. Our findings provide the first evidence that prevention of disability in old age should begin early in midlife, especially for women from manual occupation households.
Cigarette pack-years among smokers (upper x-axis shows percentiles) and frequency. 
The adverse effects of smoking on individual medical conditions are well known; however, the cumulative effect of smoking on physical performance is not well characterized, particularly in midlife. In the British 1946 Birth Cohort Study, cigarette pack-years were examined with standing balance, chair rising, grip strength, and an overall composite index. Pack-years were calculated from data collected at ages 20, 25, 31, 36, 43, and 53 years, whereas physical performance, cognitive function, anthropometry, and spirometry were assessed at age 53 years in 2,394 men and women. Regression and cubic splines were used to assess the relationship between pack-years and physical performance. Greater pack-years smoked were associated with lower overall physical performance and lower performance in standing balance and chair rising; however, there was no association with grip strength. For every 10 pack-years smoked, the overall physical performance index decreased by 0.11 SD (95% confidence interval: 0.07-0.15, p < .001), standing balance time decreased by 0.09 SD (0.05-0.13), and the reciprocal of chair rise time decreased by 0.11 SD (0.07-0.16). Adjustment for education, social class, lung function, cognitive function, and medical conditions attenuated the effect, but pack-years remained significantly associated with standing balance and chair rising time. Lifetime cigarette pack-years are strongly related to physical performance in the fifth decade of life, suggesting that smokers will enter older adulthood with decreased physiological reserve. As smoking prevalence remains high in many developed countries and is rapidly growing in developing countries, these findings underscore the need for effective smoking cessation and prevention programs.
Natural logarithm of age-specific death rate (number of deaths per person-year at a given age): an artificial example, in which the loganth­ mic mortality is a quadratic function of age. 
It has been widely supposed that human mortality from all causes increases with age nearly exponentially (at a constant rate) through adult ages except for very old ages, and that this exponential increase also holds fairly well for most major causes of death (CODs). However, the present analysis of death registration data for Japan, 1951–1990, reveals that the rate of age-related relative increase in mortality (the life table aging rate) changes with age significantly and systematically for many CODs. Above age 75, the mortality increase decelerates for most CODs; under age 75, it remains at a relatively stable pace for ischemic heart disease, decelerates for most major cancers, and accelerates for diseases related to a declining ability to maintain homeostasis (pneumonia, bronchitis, influenza, gastroenteritis, and heart failure). These results seem to suggest that significantly different types of senescent processes may underlie atherogenesis, oncogenesis, and immunosenescence.
Determining the biological limits to human longevity is more difficult than for most other species because humans are long-lived. Consequently, mortality data, such as from the U.S. vital statistics system, which have been available for a long time (relative to most epidemiological studies) and have large numbers of cases, including deaths reported to advanced ages, are important in studying human longevity-though care must be exercised in dealing with error in age reporting. Furthermore, it is unlikely that free-living humans can realize as much of their biological endowment for longevity as animals living in a highly controlled experimental environment. We examined changes, 1960 to 1990, in U.S. White male and female extinct cohort life tables and age at death distributions to (a) examine evidence for the effects of a biological life span limit in current U.S. mortality patterns and (b) produce lower bound estimates of that limit.
Cerebrovascular diseases are a common cause of mortality, morbidity, and hospitalization among older adults. However, the long-term national trends in cerebrovascular disease-related hospitalizations in this age group are not well known. We used the National Center for Health Statistics trend data from the National Hospital Discharge Surveys (1970-2000) to determine incidence of cerebrovascular disease-related hospitalizations among persons 65 years and older in the United States. Only patients discharged with a primary discharge diagnosis of cerebrovascular disease were included. We estimated rates of hospitalization per 1000 civilian residents 65 years and older, for all patients and stratified by age, sex, and race. Among persons 65 years of age and older, the total number of cerebrovascular disease-related hospitalizations increased from 372,000 in 1970 to 711,000 in 2000. However, the rates of hospitalization due to cerebrovascular disease remained unchanged at 20.7/1000 in 1970 and 20.4/1000 in 2000. The rates for persons 75-84 years and >85 years were, respectively, 2 and 3 times higher than that for persons 65-74 years throughout the study period. Rates for men and women were comparable and stable during the study period. Rates for African Americans, in contrast, increased from 14/1000 in 1970 to 20.6/1000 in 2000, peaking in 1985 (27.4/1000). The overall rates of hospitalization due to cerebrovascular disease remained high yet stable. However, the absolute number of hospitalizations due to cerebrovascular disease increased considerably, with potential for serious social, financial, and public health implications for the coming decades.
Declines in chronic disability were observed in the National Long Term Care Survey (NLTCS) 1982 to 1994. We analyzed the 1982, 1984, 1989, and 1994 NLTCS to identify the dimensions of chronic disability from multivariate analyses of a rich battery of measures of the ability (or inability) to perform specific activities. Changes over time in the prevalence of individual disability dimensions can be tracked to evaluate the rate of age-related losses of specific functions, 1982-1994. Seven dimensions described changes in the age dependence of 27 activities of daily living, instrumental activities of daily living, and physical performance measures in community and institutional resident elderly individuals over the 12 year period. Adjusted for age, the healthiest dimension with the best physical function experienced the largest increase in prevalence (3.3%) implying a decline in age-related disability. Disability declines were correlated with reductions in select health conditions (e.g., dementia and circulatory disease) over the study period.
Authorities recommend radiation therapy after breast-conserving surgery for breast cancer. Numerous studies have reported that older women diagnosed with breast cancer are less likely to receive radiation after breast-conserving surgery. It is unclear how care of older women with breast cancer has changed over time. Women with local or regional stage breast cancer diagnosed between 1983-1995 were identified from the Surveillance, Epidemiology, and End Results (SEER) Cancer Registries. The treatment information in SEER includes type of surgical procedures and receipt of radiation therapy. There were small increases in the percentage of women receiving breast-conserving surgery during the 1980s followed by substantial increases in the 1990s. Age was a major factor in determining receipt of radiation therapy after breast-conserving surgery. A large increase in use of radiotherapy after surgery was observed in women aged > or = 75, from below 30% in 1983 to over 50% in 1995. Women aged > or = 75 diagnosed in 1992-1995 were 1.76 and 2.34 times more likely to receive radiation for local and regional stage respectively, as compared to those in 1983-1987. There was no increase in use of radiation for women aged < 65. There has been a substantial increase in use of breast-conserving surgery and in receipt of radiation therapy after breast-conserving surgery in older women. However, there was a net increase in the percentage of all women with breast cancer who received this surgery without radiotherapy, due to the large increase in the overall percentage of women receiving this surgery.
Factors associated with being hospitalized with indications of prostate cancer were examined. A secondary analysis of the older men in the Longitudinal Study on Aging (LSOA) used baseline (1984) interview data and Medicare hospital claims for 1984 through 1991. The analytic sample consisted of 2254 men who were 70 to 95 years old (mean 75.8 years) at baseline and who were self-respondents to the LSOA. Case-identification involved primary prostate cancer (ICD9-CM code 185) and personal history of prostate cancer (ICD9-CM code V10.46) hospital discharge diagnoses. Multivariable logistic regression techniques were used. There were 154 cases (6.8%) of prostate cancer, including 109 identified by active diagnostic codes only, 15 identified by personal history codes only, and 30 identified by both. No associations with age, race, or ethnicity were observed. Being hospitalized with indications of prostate cancer was more likely in the presence of a history of cancer at any site, urinary control problems, greater body mass, maximum social interaction, or living in core Standard Metropolitan Statistical Area counties. Men who regularly attended religious services, had not seen a physician for 2 years, and did not feel in control of their health were less likely to have been hospitalized with indications of prostate cancer. These data suggest that the traditional associations between prostate cancer and age, race, and ethnicity do not apply to being hospitalized with indications of the disease among older men. However, body mass, history and symptoms, personal beliefs, access, and geographic practice patterns are associated with being hospitalized with indications of prostate cancer.
United States trends in the prevalence of hearing impairment have not been reported. These trends could be rising due to changes in environmental noise exposure; alternatively, rates could be declining via a compression of morbidity hypothesis that has been postulated to be occurring in older adults residing in developed nations. The National Health Interview Survey is a continuous multistage area probability survey of the U.S. civilian noninstitutionalized population living at addressed dwellings. Adults within randomly selected households were administered a chronic conditions list that included questions about hearing impairment. Complete data were available on 107,100 white and 17,904 African-American adults aged 18 years and older in survey years 1986-1995. Race-specific rates of hearing impairment were adjusted for age and sample survey design. Annual age-adjusted rates of some hearing impairment ranged from 11.0% to 12.7% in whites and 5.9% to 8.5% in African Americans. Rates of severe bilateral hearing impairment in these race groups were 0.7% to 1.1% and 0.1% to 0.5%, respectively. There was no evidence of change in rates of hearing impairment among participants stratified by race and 10-year age groups. Reported rates of hearing impairment remained relatively stable in the U.S. noninstitutionalized population from 1986 to 1995. There was no evidence of change in rates in adults grouped into 10-year age groups. Population-based studies designed to include clinical and self-reported measures of hearing impairment are needed to further examine trends in hearing impairment.
Disability-free life expectancy and life expectancy with disability, in participants aged 65 years and over. Spain, 1986 and 1999. a ) men; b ) women. 
Number and Percentage of Population With Disability in Participants Aged 65 Years and Older, by Educational Level: Spain 1986 and 1999
Percentage of Life Expectancy With Disability in Participants Aged 65 Years and Older: Spain 1986 and 1999 Participants % Life Expectancy With Disability 1986 1999
This paper examines recent trends in the prevalence of disability and disability-free life expectancy in the population aged 65 years and older in Spain. Data were drawn from two National Disability, Impairment and Handicap Surveys conducted in 1986 and 1999. Only severe disability was studied, and disabilities overcome through use of external technical aids were included. In the period 1986--1999, a relative annual decline of 3.7% in overall disability was observed for men. The decline was somewhat less marked in women, participants aged 75 years and older, and those with the lowest educational level. In men, there was a relative annual decline of just over 3% in walking and hearing disabilities, of under 1% in seeing and cognitive disabilities, and a slight rise in self-care disability. Trends among women were similar, though self-care disability rose by 1.78%. In the period 1986--1999, total and disability-free life expectancy rose across all age groups in both sexes. Among men aged 65 years, the proportion of life expectancy with disability fell from 42.1% in 1986 to 21.6% in 1999; the comparable figures for women were 49.8% in 1986 and 30.6% in 1999. Indeed, a reduction in life expectancy with disability was observed even among persons aged 80 years and older. From 1986 through 1999, prevalence of severe disability among Spanish elderly persons decreased substantially, and the duration of life with disability was compressed between a later onset and the time of death. Among women, however, self-care disability--the type of disability requiring most social resources for its attention--underwent a sharp rise.
Background: Older adults frequently have several chronic health conditions which require multiple medications. We illustrated trends in prescription medication use over 20 years in the United States, and described characteristics of older adults using multiple medications in 2009-2010. Methods: Participants included 13,869 adults aged 65 years and older in the National Health & Nutrition Examination Survey (1988-2010). Prescription medication use was verified by medication containers. Potentially inappropriate medications were defined by the 2003 Beers Criteria. Results: Between 1988 and 2010 the median number of prescription medications used among adults aged 65 and older doubled from 2 to 4, and the proportion taking ≥5 medications tripled from 12.8% (95% confidence interval: 11.1, 14.8) to 39.0% (35.8, 42.3).These increases were driven, in part, by rising use of cardioprotective and antidepressant medications. Use of potentially inappropriate medications decreased from 28.2% (25.5, 31.0) to 15.1% (13.2, 17.3) between 1988 and 2010. Higher medication use was associated with higher prevalence of functional limitation, activities of daily living limitation, and confusion/memory problems in 2009-2010, although these associations did not remain after adjustment for covariates. In multivariable models, older age, number of chronic conditions, and annual health care visits were associated with increased odds of using both 1-4 and ≥5 medications. Additionally, body mass index, higher income-poverty ratio, former smoking, and non-black non-white race were associated with use of ≥5 medications. Conclusions: Prescription medication use increased dramatically among older adults between 1988 and 2010. Contemporary older adults on multiple medications have worse health status compared with those on less medications, and appear to be a vulnerable population.
Top-cited authors
Stephen Kritchevsky
  • Wake Forest School of Medicine
Linda P Fried
  • Columbia University
Eleanor M Simonsick
  • National Institute on Aging
Peggy Mannen Cawthon
  • California Pacific Medical Center Research Institute
Robert R Mclean
  • Hebrew SeniorLife