A third of those over 80 years of age are likely to have dementia, the lack of a cure requires efforts directed at prevention and delaying the age of onset. We argue here for the importance of understanding the cognitive ageing process, seen as the decline in various cognitive functions from adulthood to old age. The impact of age on cognitive function is heterogeneous and the identification of risk factors associated with adverse cognitive ageing profiles would allow well-targeted interventions, behavioural or pharmacological, to delay and reduce the population burden of dementia. A shift away from binary outcomes such as dementia assessed at one point in time in elderly populations to research on cognitive ageing using repeated measures of cognitive function and starting earlier in the life course would allow the sources of variability in ageing to be better understood.
Alzheimer’s disease; Dementia; Cognitive ageing
A third of those over 80 years of age are likely to have dementia, the lack of a cure requires efforts directed at prevention and delaying the age of onset. We argue here for the importance of understanding the cognitive ageing process, seen as the decline in various cognitive functions from adulthood to old age. The impact of age on cognitive function is heterogeneous and the identification of risk factors associated with adverse cognitive ageing profiles would allow well targeted interventions, behavioural or pharmacological, to delay and reduce the population burden of dementia. A shift away from binary outcomes such as dementia assessed at one point in time in elderly populations to research on cognitive ageing using repeated measures of cognitive function and staring earlier in the lifecourse would allow the sources of variability in ageing to be better understood.
Aging; Alzheimer Disease; epidemiology; physiopathology; Cognition; Dementia; diagnosis; epidemiology; physiopathology; prevention & control; therapy; France; epidemiology; Humans; Prevalence; Risk Factors; World Health Organization
Calorie restriction (CR) is the most widely studied intervention protecting from the adverse effects of aging. Almost all prior studies have examined the effects of CR initiated in young animals. Studies examining the effects of CR on development of aging cardiomyopathy found only partial prevention. The major goal of this study was to determine whether CR initiated after aging cardiomyopathy developed could reverse the cardiomyopathy. Aging cardiomyopathy in 2-year-old mice was characterized by reduced left ventricular (LV) function, cardiac hypertrophy, and increased cardiac apoptosis and fibrosis. When short-term (2 months) CR was initiated after aging cardiomyopathy developed in 20-month-old mice, the decrease in cardiac function, and increases in LV weight, myocardial fibrosis and apoptosis were reversed, such that the aging hearts in these mice were indistinguishable from those of young mice or mice where CR was initiated in young mice. If apoptosis was the mechanism for protecting against aging cardiomyopathy, then total myocyte numbers should have reverted to normal with CR, but did not. However, the alterations in cytoskeletal proteins, which contribute to aging cardiomyopathy, were no longer observed with CR. This is the first study to demonstrate complete prevention of aging cardiomyopathy by CR and, more importantly, that instituting this intervention even later in life can rapidly correct aging cardiomyopathy, which could have important therapeutic implications.
Electronic supplementary material
The online version of this article (doi:10.1007/s11357-012-9508-5) contains supplementary material, which is available to authorized users.
Calorie restriction; Aging; Cardiomyopathy; Apoptosis; Myocyte loss
Due to ameliorated surgery as well as better immunosuppression, the recipient age after liver transplantation has been extended over the past years. This study aimed to investigate the health related quality of life after liver transplantation in recipients beyond 60 years of age. The SF-36 was used to evaluate the recipients’ health-related quality of life as standardized tool. It comprises 36 items that are attributed to 8 subscales attributed to 2 components: the physical component score and the mental component score. Differences in the health-related quality of life between the included aged recipients and age-matched general population as well as among female and male recipients. Aged recipients showed significantly lower scores in physical functioning (29 vs. 76, p = 0.001), role physical (42 vs. 73, p = 0.003), bodily pain (34 vs. 71, p = 0.003), general health (28 vs. 59, p = 0.001), vitality (25 vs. 61, p = 0.001), social functioning (36 vs. 87, p = 0.001), role emotional (46 vs. 89, p = 0.001) as well as the physical component score (28 vs. 76, p = 0.001). Aged female recipients showed lower results as compared to males in social functioning, physical functioning, role physical, and social functioning (p = 0.03 respectively) but comparable results in the remaining. Quality of life seems to be an issue among aged recipients and should be assessed on a regular basis.
Liver transplantation; Immunosuppression; Quality of life; SF-36
Strength training seems to be an interesting approach to counteract decreases that affect knee extensor strength, muscle mass and muscle quality (force per unit of muscle mass) associated with ageing. However, there is no consensus regarding the changes in muscle mass and their contribution to strength during periods of training and detraining in the elderly. Therefore, this study aimed at verifying the behaviour of knee extensor muscle strength, muscle volume and muscle quality in elderly women in response to a 12-week strength training programme followed by a similar period of detraining. Statistical analysis showed no effect of time on muscle quality. However, strength and muscle volume increased from baseline to post-training (33 and 26 %, respectively). After detraining, the knee extensor strength remained 12 % superior to the baseline values, while the gains in muscle mass were almost completely lost. In conclusion, strength gains and losses due to strength training and detraining, respectively, could not be exclusively associated with muscle mass increases. Training-induced strength gains were partially maintained after 3 months of detraining in elderly subjects.
Strength training; Knee extensor muscle; Muscular adaptations
Mice deficient in Cu,Zn superoxide dismutase (Sod1−/− mice) demonstrate elevated oxidative stress associated with rapid age-related declines in muscle mass and force. The decline in mass for muscles of Sod1−/− mice is explained by a loss of muscle fibers, but the mechanism underlying the weakness is not clear. We hypothesized that the reduced maximum isometric force (Fo) normalized by cross-sectional area (specific Fo) for whole muscles of Sod1−/− compared with wild-type (WT) mice is due to decreased specific Fo of individual fibers. Force generation was measured for permeabilized fibers from muscles of Sod1−/− and WT mice at 8 and 20 months of age. WT mice were also studied at 28 months to determine whether any deficits observed for fibers from Sod1−/− mice were similar to those observed in old WT mice. No effects of genotype were observed for Fo or specific Fo at either 8 or 20 months, and no age-associated decrease in specific Fo was observed for fibers from Sod1−/− mice, whereas specific Fo for fibers of WT mice decreased by 20 % by 28 months. Oxidative stress has also been associated with decreased maximum velocity of shortening (Vmax), and we found a 10 % lower Vmax for fibers from Sod1−/−compared with WT mice at 20 months. We conclude that the low specific Fo of muscles of Sod1−/− mice is not explained by damage to contractile proteins. Moreover, the properties of fibers of Sod1−/− mice do not recapitulate those observed with aging in WT animals.
Contractility; Oxidative stress; Permeabilized fiber; Skeletal muscle; Specific force
We aimed to assess the association between red blood cell distribution width (RDW) and mortality in patients enrolled by a Geriatric Department. One hundred twenty-two patients were followed up during 5 years. The primary end point was all-cause mortality, and hazard ratios were estimated using a Cox proportional hazard model. Higher RDW values were strongly associated with an increased risk of death. Survival curves across RDW quartiles were statistically different according to the log-rank test (p = 0.017). The first quartile presented higher probability of survival compared to the last one. The gradient from lower to higher risk across quartiles was clear both in the 5-year mortality risk and in the mortality rate per 100 person-years, which ranged from 18.9 to 42.6. However, in the Cox regression model after adjusting for age, severity, and other factors, excess risk was only observed in the highest RDW quartile, with a hazard ratio of 2.24 (CI95% 1.13–4.42) vs the first quartile. RDW is a good predictor of mortality in hospitalized older adults beyond those with cardiovascular risk factors, and it could serve as an integrative measure of multiple clinical and subclinical processes simultaneously occurring in complex patients.
Aging; Red cell distribution width; Mortality; Risk factors; Life Sciences; Molecular Medicine; Geriatrics/Gerontology; Cell Biology
Verbal comprehension is critical to the success of medical counseling. Here, we tested how age and vascular risk factors affect the ability to understand complex instructions. Verbal comprehension, cognitive functions, and vascular risk factors were assessed in 39 mid- and 38 late-life community-dwelling individuals (48 to 59 years and >59 years of age, respectively). To test for verbal comprehension, we used a modified version of the Token Test (TT). In midlife individuals, education (β = 0.572, p < 0.05) was the only predictor for extended-TT performance. In late-life individuals, age (β = −1.015, p < 0.001) and body mass index (β = −0.651, p = 0.003) were significantly correlated with extended-TT performance and explained 50% of the variance in extended-TT performance (adjusted R2 = 0.503). This relation is only partly explained by conventional neuropsychological measures as the ones used in our test battery. These results indicate that aging and overweight impair comprehension of complex instructions. Therefore, medical counseling appropriate for midlife individuals may be less successful in elderly people and particularly in those with metabolic disturbances.
Token test; Language comprehension; Age; Vascular risk factor; Medical counseling
We studied the A55T, E164K, I225T, K153R and P198A variants in the myostatin (GDF8) gene, muscle strength and mass, and physical function during daily living in 41 nonagenarians [33 women, age range, 90, 97]. No participant carried a mutant allele of the aforementioned variants, except three participants (all women), who carried the R allele of the K153R polymorphism, with one of them (woman aged 96 years) being homozygous. Overall, in KR women muscle phenotype values (1RM leg press and estimated muscle mass) were low-to-normal compared to the whole group (∼25th–50th percentile), and their functional capacity (Barthel and Tinetti tests) was normal. In the woman bearing the RR genotype, values of muscle mass and functional capacity were below the 25th percentile. She is the first RR Caucasian whose phenotype has been characterised specifically. In summary, heterozygosity for the GDF8 K153R polymorphism does not seem to exert a negative influence on the muscle phenotypes of women who are at the end of the human lifespan, yet homozygosity might do so. More research on larger cohorts of nonagenarians is needed to corroborate the present findings.
Activities of daily living; GDF-8; Muscle strength; Nonagenarians
Patients with diabetes mellitus show increased risk of infectious disease as well as disturbances in innate immunity. In critical care settings, hyperglycemia is associated with increased risk of sepsis. It is unclear whether elevated glucose concentrations and innate immunity are associated in a non-clinical setting. We aimed to assess the association between glucose concentrations and innate immune response in the oldest old, who are at increased risk of both disturbed glucose metabolism as well as infectious disease. This study was part of the Leiden 85-plus Study. In 562 subjects aged 85 years old of the general population, venous blood samples were taken for measurement of morning glucose, C-reactive protein (CRP) and glycated hemoglobin (HbA1c). The innate immune response was assessed by performing ex vivo whole blood lipopolysaccharide (LPS) stimulation for production capacity of tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), interleukin 1-beta (IL1-β), interleukin 10 (IL-10) and interleukin 1 receptor antagonist (IL-1Ra). Using linear regression analysis, cross-sectional analysis between glucose and cytokine production capacity was performed. We found a significant negative association between glucose concentrations, but not HbA1c, and cytokine response capacity in four out of five measured cytokines (all p < 0.05). Both glucose and HbA1c were positively associated with circulating levels of CRP. Higher glucose concentrations in non-diabetic elderly are associated with lower innate immune response. As elderly show increased vulnerability for disturbances in glucose metabolism as well as infectious disease, this relation could be of clinical significance.
Aging; Glucose; Cytokine response; Innate immunity
The average human lifespan has increased throughout the last century due to the mitigation of many infectious diseases. More people now die of age-related diseases than ever before, but these diseases have been resistant to elimination. Progress has been made in treatments and preventative measures to delay the onsets of these diseases, but most cancers and vascular diseases are still with us and they kill about the same fraction of the population year after year. For example, US Caucasian female deaths from breast plus genital cancers have remained a fairly constant ~7% of the age-related disease deaths from 1938 to 1998 and have been consistently ~2-fold greater than female colon plus rectal cancer deaths over that span. This type of stability pattern pervades the age-related diseases and suggests that intrinsic properties within populations determine these fractions. Recognizing this pattern and deciphering its origin will be necessary for the complete understanding of these major causes of death. It would appear that more than the random processes of aging drive this effect. The question is how to meaningfully approach this problem. This commentary discusses the epidemiological and aging perspectives and their current limitations in providing an explanation. The age of bioinformatics offers hope, but only if creative systems approaches are forthcoming.
Disease; Aging; Epidemiology; Bioinformatics; Genetics; Failure mechanisms
The high-growth (HG) phenotype in mice is characterized by a 30–50% postweaning overgrowth with a substantial increase in plasma insulin-like growth factor I (IGF1) levels, which is directly related to a deletion (hg) on chromosome 10 that includes the suppressor of cytokine signaling 2 (Socs2) gene. Reduced plasma IGF1 levels have been associated with extended lifespan in mice, although the aging-related effects of abnormally high IGF1 levels without elevated growth hormone levels have never been assessed in mammals. Within this context, the hg deletion was introgressed into C57BL/6J (B6) and FVB backgrounds, and a survival analysis was performed on the longevity records of 200 B6 (91 wild-type and 109 homozygous hg mutants) and 69 FVB (32 wild-type and 37 hg mutants) mice. Longevity was examined using a piecewise Weibull proportional hazards model solved through a Bayesian perspective and Markov chain Monte Carlo sampling. Lifespan was significantly reduced in both strains in homozygous hg mice, with a death risk between 3.689 (B6) and 4.347 (FVB) times higher than in wild-type mice (non-overlapped highest posterior density regions at 95%). These results highlight the effects of the Socs2 gene on aging regulation, likely related with variations described in plasma IGF1 levels. This result is consistent with previous research in dwarf mutant mice and other species, and characterizes the HG mutant mice as a unique and interesting animal model for accelerated aging research.
Cytokine signaling 2; Growth hormone; Insulin-like growth factor I; Lifespan; Mice; Survival analysis
Receptor-interacting protein (RIP) is a well-characterized coregulator for nuclear receptors. Here, we report the expression of RIP as two isoforms with molecular weights of 140 kDa and 137 kDa in liver and kidney, but only as one isoform of 140 kDa in lung, adipose tissue, prostate and testis of mice. The levels of both the isoforms decreased in liver and kidney of old mice compared with adult mice. The expression of RIP140 in kidney was relatively lower in old males than females. In contrast, adipose tissue showed remarkably higher levels of RIP140 in old than adult mice of both sexes. Thus, the expression of RIP varied with the type of tissue, sex and age of mice, suggesting differences in its function as a coregulator.
Receptor-interacting protein; Coregulator; Expression; Aging; Sex; Mouse
Microarray-based comparisons of long-lived and normal mouse strains represent a promising approach for dissecting the basis of lifespan extension in higher organisms. Recently, Boylston et al. (2006) generated a genome-wide data set that allowed expression levels of Snell (Pit1dw/dw) and Ames (Prop1df/df) long-lived mice to be compared with age-matched control mice across different ages (6–24 months). Longevity-associated genes were identified as those genes exhibiting differential expression between long-lived and normal mice at every age examined. In this communication, an alternative approach to identifying longevity-associated genes is suggested and applied to the data sets considered by Boylston et al. (2006). Longevity-associated genes are defined as those exhibiting significant genotype-by-age interaction with respect to expression levels of long-lived and normal mice, and a total of 63 longevity-associated genes are identified. This approach may lend greater confidence to the inference that expression of identified genes specifically underlies aging differences between long-lived and normal genotypes.
Aging; Ames; Dwarf; Lifespan; Microarray; Pit1dw; Prop1df; Snell
We considered a Gompertzian model for the population dynamics of Eisenia andrei case-cohorts in artificial OECD soil under strictly controlled conditions. The earthworm culture was kept between 18 and 22°C at a constant pH of 5.0. In all, 77 lumbricids were carefully followed for almost 9 years, until the oldest died. The Eisenia median longevity is 4.25 years and the oldest specimen was 8.73 years. Eisenia cocoons were hand-sorted every 3 weeks, washed in distilled water, placed in Petri dishes, and counted. Regular removal did not reduce breeding. Each fertile cocoon contained on average two or three embryos. The failure rates (mortality and infertility percentages) are smooth power functions where the rate at time (n + 1) captured most of the phenomenology of the previous rate at time n, as expected by the considered law, but not at both the beginning and the end of this long-term laboratory study.
Allometric scaling; Body-mass values; Cocoon fertility; Eisenia; Failure rates; Gompertz