Handgrip strength and mortality in the oldest old population: the Leiden 85-plus study

Background

Poor muscular strength has been shown to be associated with increased morbidity and mortality in diverse samples of middle-aged and elderly people. However, the oldest old population (i.e., over 85 years) is underrepresented in such studies. Our objective was to assess the association between muscular strength and mortality in the oldest old population.

Methods

We included 555 participants (65% women) from the Leiden 85-plus study, a prospective population-based study of all 85-year-old inhabitants of Leiden, Netherlands. We measured the handgrip strength of participants at baseline and again at age 89 years. We collected baseline data on comorbidities, functional status, levels of physical activity, and adjusted for potential confounders. During the follow-up period, we collected data on mortality.

Results

During a follow-up period of 9.5 years (range 8.5–10.5 years), 444 (80%) participants died. Risk for all-cause mortality was elevated among participants in the lowest tertile of handgrip strength at age 85 years (hazard ratio [HR] 1.35, 95% confidence interval [CI] 1.00–1.82, p = 0.047) and the lowest two tertiles of handgrip strength at age 89 years (HR 2.04, CI 1.24–3.35, p = 0.005 and HR 1.73, CI 1.11–2.70, p = 0.016). We also observed significantly increased mortality among participants in the tertile with the highest relative loss of handgrip strength over four years (HR 1.72, CI 1.07–2.77, p = 0.026).

Interpretation

Handgrip strength, a surrogate measurement of overall muscular strength, is a predictor of all-cause mortality in the oldest old population and may serve as a convenient tool for prognostication of mortality risk among elderly people.The fastest growing segment of the elderly population is the group older than 85 years, which is classified as the oldest old age group.^1,2 The average rate of growth of this group is reported to be 3.8% annually at a global level. By 2050, the oldest old age group will account for one-fifth of all older persons.²Inactivity is a major problem in this age group, owing to an increased prevalence of medical comorbidities and physical disability with age. Age-related stereotypes and misconceptions (e.g., that older people are invariably unhealthy), coupled with a perceived lack of benefits provided by physical activity, can also represent obstacles to exercise among the oldest old population.The predisposing influence of a sedentary lifestyle on age-related cardiometabolic diseases (i.e., obesity, type 2 diabetes mellitus, hypertension and coronary artery disease) is well established. Evidence of the protective effects of physical activity against certain cancers, falls and mental health problems is accumulating.^3,4 Lack of exercise is also a significant risk factor for sarcopenia,^5,6 a progressive loss of skeletal muscle mass and strength with aging.⁷ Sarcopenia is highly prevalent among those aged 80 years and older, with reported rates exceeding 50%.⁸ Reduced muscular strength is associated in turn with outcomes such as physical disability,^9,10 cognitive decline¹¹ and mortality.^12,13Handgrip strength, a simple bedside tool, has been shown to be a valid surrogate measurement of overall muscular strength.^14,15 A recent systematic review has shown that low handgrip strength is associated consistently with premature mortality, disability and other health-related complications among various samples of middle-aged and older people.¹⁶ Despite its prognostic value, handgrip dynamometry is rarely used in routine geriatric assessment. Epidemiologic studies evaluating the relation in the population of the oldest old are also lacking. We tested the association between handgrip strength and mortality in a prospective population-based study of the oldest old age group. We obtained approval for our study from the Medical Ethical Committee of the Leiden University Medical Center, and informed consent from all participants.     

Barriers encountered during enrollment in an internet-mediated randomized controlled trial

Background

Research evidence from observational studies suggests that cognitive activity reduces the risk of cognitive impairment in later life as well as the rate of cognitive decline of people with dementia. The Promoting Healthy Ageing with Cognitive Exercise (PACE) study has been designed to determine whether a cognitive activity intervention decreases the rate of cognitive decline amongst older adults with mild cognitive impairment (MCI).

Methods/Design

The study will recruit 160 community-dwelling men and women aged 65 years of age or over with mild cognitive impairment (MCI). Participants will be randomly allocated to two treatment groups: non-specific education and cognitive activity. The intervention will consist of ten 90-minute sessions delivered twice per week over a period of five weeks. The primary outcome measure of the study is the change from baseline in the total score on the Cambridge Cognitive Score (CAMCOG). Secondary outcomes of interest include changes in memory, attention, executive functions, mood and quality of life. Primary endpoints will be collected 12, 52 and 104 weeks after the baseline assessment.

Discussion

The proposed project will produce the best available evidence on the merits of increased cognitive activity as a strategy to prevent cognitive decline among older adults with MCI. We anticipate that the results of this study will have implications for the development of evidence-based preventive strategies to reduce the rate of cognitive decline amongst older people at risk of dementia.

Trial registration

ACTRN12608000556347     

Sentinel lymph node biopsy for high-risk cutaneous squamous cell carcinoma: clinical experience and review of literature

Background

The elderly population has increased in many countries. Indications for cancer treatment in elderly patients have expanded, because surgical techniques and medical management have improved remarkably. Pancreaticoduodenectomy (PD) requires high-quality techniques and perioperative management methods. If it is possible for elderly patients to withstand an aggressive surgery, age should not be considered a contraindication for PD. Appropriate preoperative evaluation of elderly patients will lead to their safer management. The purpose of the present study was to evaluate the safety of PD in patients older than 75 years and to show the influence of advanced age on the morbidity and mortality associated with this operation.

Patients and methods

Subjects were 98 patients who underwent PD during the time period from April 2005 to April 2011. During this study, 31 patients were 75 years of age or older (group A), and the other 67 patients were less than 75 years old (group B). Preoperative demographic and clinical data, surgical procedure, pathologic diagnosis, postoperative course and complication details were collected prospectively and they were analyzed in two group.

Results

There was no statistical difference between patient groups in terms of gender, comorbidity, preoperative drainage, diagnosis, or laboratory data. Preoperative albumin values were lower in group A (P = 0.04). The mean surgical time in group A was 408.1 ± 73.47 min. Blood loss and blood transfusion were not significantly different between both groups. There was no statistical differences in mortality rate (P = 0.14), morbidity rate (P = 0.43), and mean length of hospital stay (P = 0.22) between both groups. Long-term survival was also no statistically significant difference between the two groups using the log-rank test (P = 0.10).

Conclusion

It cannot be ignored that the elderly population is getting larger. We must investigate the management of elderly patients after PD and prepare further for more experiences of PD. If appropriate surgical management is provided to elderly patients, we suggest that PD will lead to no adverse effects after surgery, and PD can be performed safely in elderly patients. We conclude that age should not be a contraindication to PD.     

Incidence and Predictors of Multimorbidity in the Elderly: A Population-Based Longitudinal Study

Background

We aimed to calculate 3-year incidence of multimorbidity, defined as the development of two or more chronic diseases in a population of older people free from multimorbidity at baseline. Secondly, we aimed to identify predictors of incident multimorbidity amongst life-style related indicators, medical conditions and biomarkers.

Methods

Data were gathered from 418 participants in the first follow up of the Kungsholmen Project (Stockholm, Sweden, 1991–1993, 78+ years old) who were not affected by multimorbidity (149 had none disease and 269 one disease), including a social interview, a neuropsychological battery and a medical examination.

Results

After 3 years, 33.6% of participants who were without disease and 66.4% of those with one disease at baseline, developed multimorbidity: the incidence rate was 12.6 per 100 person-years (95% CI: 9.2–16.7) and 32.9 per 100 person-years (95% CI: 28.1–38.3), respectively. After adjustments, worse cognitive function (OR, 95% CI, for 1 point lower Mini-Mental State Examination: 1.22, 1.00–1.48) was associated with increased risk of multimorbidity among subjects with no disease at baseline. Higher age was the only predictor of multimorbidity in persons with one disease at baseline.

Conclusions

Multimorbidity has a high incidence at old age. Mental health-related symptoms are likely predictors of multimorbidity, suggesting a strong impact of mental disorders on the health of older people.     

Hypertonic saline reduces inflammation and enhances the resolution of oleic acid induced acute lung injury

Background

The association between bronchial obstruction severity and mortality in Chronic Obstructive Pulmonary Disease (COPD) is well established, but it is unknown whether disease-specific health status measures and multidimensional assessment (MDA) have comparable prognostic value.

Methods

We analyzed data coming from the Salute Respiratoria nell'Anziano (Respiratory Health in the Elderly – SaRA) study, enrolling elderly people attending outpatient clinics for respiratory and non-respiratory problems. From this population we selected 449 patients with bronchial obstruction (77.3% men, mean age 73.1). We classified patients' health status using tertiles of the Saint George Respiratory Questionnaire (SGRQ) and a MDA including functional (the 6' walking test, WT), cognitive (Mini-Mental State Examination, MMSE) and affective status (Geriatric Depression Scale, GDS). The agreement of the classification methods was calculated using the kappa statistic, and survival associated with group membership was evaluated using survival analysis.

Results

Pulmonary function, expressed by the FEV1, worsened with increasing SGRQ or MDA scores. Cognitive function was not associated with the SGRQ, while physical performance and mood status were impaired only in the highest tertile of SGRQ. A poor agreement was found between the two classification systems tested (k = 0.194). Compared to people in the first tertile of SGRQ score, those in the second tertile had a sex-adjusted HR of 1.22 (0.75 – 1.98) and those in the third tertile of 2.90 (1.92 – 4.40). The corresponding figures of the MDA were 1.49 (95% CI 1.02 – 2.18) and 2.01 (95% CI: 1.31 – 3.08). After adjustment for severity of obstruction, only a SGRQ in the upper tertile was associated with mortality (HR: 1.86; 95% CI: 1.14 – 3.02).

Conclusion

In elderly outpatients with mild-moderate COPD, a disease-specific health status index seems to be a better predictor of death compared to a MDA.     

Soil drainage and phosphorus depletion contribute to retrogressive succession along a New Zealand chronosequence

Background and aims

Models of retrogressive succession have emphasised the role of phosphorus (P) depletion in driving biomass loss on surfaces of increasing geologic age, but the influence of impeded drainage on old surfaces has received much less attention. We tested whether poor drainage contributed to changes in ecosystem properties along a 291,000-year chronosequence in New Zealand (the Waitutu chronosequence).

Methods

Soil and ecosystem properties were measured at 24 evenly distributed points within each of eight 1.5 ha plots located on young, intermediate and old surfaces. Regression analyses tested whether drainage, in addition to P, affected ecosystem functioning. A complementary fertilization experiment tested whether P was indeed limiting on the most nutrient-depleted sites.

Results

Most phosphorus depletion occurred in the early stages of pedogenesis (within 24,000 years), and the older surfaces were similar in soil-P contents, whereas drainage was initially good but became increasingly impeded with surface age. In the fertilizer experiment, species showed positive responses to both nitrogen (N) and P addition on the oldest surfaces, supporting Walker and Syer’s model. However, water table depth was also found to be strongly correlated with plant species composition, forest basal area, light transmission, and litter decomposition when comparisons were made across sites, emphasising that it too has strong influences on ecosystem processes.

Conclusions

Poor drainage influences the process of retrogressive succession along the Waitutu chronosequence. We discuss the implications of our work with regard to other chronosequences, suggesting that topography is likely to have strong influences on retrogressive processes.     

Are optimal levels of testosterone associated with better cognitive function in healthy older women and men?

Background

Sex steroids can positively affect the brain and from this it would follow that high levels of sex steroids could be associated with better cognitive function in older men and women.

Methods

This Healthy Ageing Study sample comprised of 521 older participants (51% women) without dementia at baseline, with an age range from 64 to 94 years. Testosterone and sex hormone binding globulin were measured using the automated Immulite 2000 and analyzed in association with baseline memory, global cognitive function and decline (assessed using the Mini-Mental Status Examination or MMSE) and controlling for potential confounds such as age, education, vascular disease, smoking, diabetes, thyroid function, and body mass index.

Results

In healthy older men and women, optimal levels of testosterone were associated with better MMSE scores at baseline. Follow-up analyses indicated that in men, low testosterone levels (OR = .94, 95% CI = .88 to 1.00) were a risk factor for a sharp cognitive decline after 2 years, perhaps indicative of dementia. Associations were independent of covariates and baseline MMSE. Conversely, women at risk for a sharp drop in cognitive function showed some evidence for higher calculated free testosterone levels at baseline.

Conclusions

Results replicate earlier cross-sectional findings that high levels of sex steroids are not associated with better cognitive function in older people. In men, age accelerated endocrinological change could be associated with dementia pathology.

General significance

These data do not support increasing testosterone levels to prevent cognitive decline in men and women over 65 years of age.     

Dopaminergic and serotonergic drug use: a nationwide register-based study of over 1,300,000 older people

Objective

To investigate the use of dopaminergic and serotonergic drugs in elderly people.

Methods

We analyzed data on age, sex and dispensed drugs for individuals aged ≥65 years registered in the Swedish Prescribed Drug Register from July to September 2008 (n = 1 347 564; 81% of the total population aged ≥65 years in Sweden). Main outcome measures were dopaminergic (enhancing and/or lowering) and serotonergic (enhancing and/or lowering) drugs and combinations of these.

Results

Dopaminergic and serotonergic drugs were used by 5.6% and 13.2% the participants, respectively. Female gender was related to use of both dopaminergic and, particularly, serotonergic drugs. Higher age was associated with use of dopamine lowering drugs and serotonergic drugs, whereas the association with use of dopamine enhancing drugs declined in the oldest old. The occurrence of combinations of dopaminergic and serotonergic drugs was generally low, with dopamine lowering + serotonin lowering drug the most common combination (1.6%). Female gender was associated with all of the combinations of dopaminergic and serotonergic drugs, whereas age showed a mixed pattern.

Conclusion

Approximately one out of ten older patients uses serotonergic drugs and one out of twenty dopaminergic drugs. The frequent use of dopaminergic and serotonergic drugs in the elderly patients is a potential problem due to the fact that aging is associated with a down-regulation of both these monoaminergic systems. Future studies are needed for evaluation of the impact of these drugs on different cognitive and emotional functions in old age.     

Identification of serum biomarkers for aging and anabolic response

Objective

With the progressive aging of the human population, there is an inexorable decline in muscle mass, strength and function. Anabolic supplementation with testosterone has been shown to effectively restore muscle mass in both young and elderly men. In this study, we were interested in identifying serum factors that change with age in two distinct age groups of healthy men, and whether these factors were affected by testosterone supplementation.

Methods

We measured the protein levels of a number of serum biomarkers using a combination of banked serum samples from older men (60 to 75 years) and younger men (ages 18 to 35), as well as new serum specimens obtained through collaboration. We compared baseline levels of all biomarkers between young and older men. In addition, we evaluated potential changes in these biomarker levels in association with testosterone dose (low dose defined as 125 mg per week or below compared to high dose defined as 300 mg per week or above) in our banked specimens.

Results

We identified nine serum biomarkers that differed between the young and older subjects. These age-associated biomarkers included: insulin-like growth factor (IGF1), N-terminal propeptide of type III collagen (PIIINP), monokine induced by gamma interferon (MIG), epithelial-derived neutrophil-activating peptide 78 (ENA78), interleukin 7 (IL-7), p40 subunit of interleukin 12 (IL-12p40), macrophage inflammatory protein 1β (MIP-1β), platelet derived growth factor β (PDGFβ) and interferon-inducible protein 10 (IP-10). We further observed testosterone dose-associated changes in some but not all age related markers: IGF1, PIIINP, leptin, MIG and ENA78. Gains in lean mass were confirmed by dual energy X-ray absorptiometry (DEXA).

Conclusions

Results from this study suggest that there are potential phenotypic biomarkers in serum that can be associated with healthy aging and that some but not all of these biomarkers reflect gains in muscle mass upon testosterone administration.     

Modelling Cognitive Decline in the Hypertension in the Very Elderly Trial [HYVET] and Proposed Risk Tables for Population Use

Introduction

Although, on average, cognition declines with age, cognition in older adults is a dynamic process. Hypertension is associated with greater decline in cognition with age, but whether treatment of hypertension affects this is uncertain. Here, we modelled dynamics of cognition in relation to the treatment of hypertension, to see if treatment effects might better be discerned by a model that included baseline measures of cognition and consequent mortality

Methodology/Principal Findings

This is a secondary analysis of the Hypertension in the Very Elderly Trial (HYVET), a double blind, placebo controlled trial of indapamide, with or without perindopril, in people aged 80+ years at enrollment. Cognitive states were defined in relation to errors on the Mini-Mental State Examination, with more errors signifying worse cognition. Change in cognitive state was evaluated using a dynamic model of cognitive transition. In the model, the probabilities of transitions between cognitive states is represented by a Poisson distribution, with the Poisson mean dependent on the baseline cognitive state.The dynamic model of cognitive transition was good (R² = 0.74) both for those on placebo and (0.86) for those on active treatment. The probability of maintaining cognitive function, based on baseline function, was slightly higher in the actively treated group (e.g., for those with the fewest baseline errors, the chance of staying in that state was 63% for those on treatment, compared with 60% for those on placebo). Outcomes at two and four years could be predicted based on the initial state and treatment.

Conclusions/Significance

A dynamic model of cognition that allows all outcomes (cognitive worsening, stability improvement or death) to be categorized simultaneously detected small but consistent differences between treatment and control groups (in favour of treatment) amongst very elderly people treated for hypertension. The model showed good fit, and suggests that most change in cognition in very elderly people is small, and depends on their baseline state and on treatment. Additional work is needed to understand whether this modelling approach is well suited to the valuation of small effects, especially in the face of mortality differences between treatment groups.

Trial Registration

ClinicalTrials.gov NCT0012281     

Success of electrocardioversion on the elderly

Background

There are two treatment strategies for medication-resistant atrial fibrillation (AF): rhythm control or rate control. It has been suggested that rate control is a valid strategy in well-tolerated AF because it does not result in increased mortality. We aimed to investigate the 1-year outcome of rhythm control in an elderly population of AF patients.

Method

The study was retrospective, using the data collected from electrocardioversions (ECV) of elderly patients and the data of their follow-up visits to the outpatient clinic. We looked for recurrence of AF within the first year after ECV. Furthermore, we investigated possible predictors of recurrence.

Results

From February 2008 till November 2011, 436 consecutive elderly patients admitted for ECV were included. The 1-year recurrence rate of AF was 51.3 %. We found that being female and a large left atrial diameter were independent predictors of recurrence.

Conclusion

The AF recurrence rate in our elderly population is comparable with reported AF recurrence rates in a younger population; we conclude that rhythm control can be regarded as the viable strategy in persistent AF in elderly patients.     

Colovaginal anastomosis: an unusual complication of stapler use in restorative procedure after Hartmann operation

Background

To support decisions about surgical treatment of elderly patients with cancer, population-based estimates of postoperative mortality (POM) rates are required.

Methods

Electronic records from the Rotterdam Cancer Registry were retrieved for octogenarians and nonagenarians who underwent resection in the period 1987–2000. POM was defined as death within 30 days of resection and both elective and emergency operations were included.

Results

In a series of 5.390 operated patients aged 80 years and older, POM rates were 0.5% for breast cancer, 1.7% for endometrial cancer and 4.2% for renal cancer. For patients with colorectal cancer, POM increased from 8% for the age group 80–84 to 13% for those 85–89 to 20% in nonagenarians. For stomach cancer, the respective figures were 11%, 20% and 44%.

Conclusion

These results show that resections can be performed at acceptable risk in selected elderly patients with cancer.     

Biogeographical and evolutionary importance of the European high mountain systems

Background

Menopause is a seemingly maladaptive life-history trait that is found in many long-lived mammals. There are two competing evolutionary hypotheses for this phenomenon; in the adaptive view of menopause, the cessation of reproduction may increase the fitness of older females; in the non-adaptive view, menopause may be explained by physiological deterioration with age. The decline and eventual cessation of reproduction has been documented in a number of mammalian species, however the evolutionary cause of this trait is unknown.

Results

We examined a unique 30-year time series of killer whales, tracking the reproductive performance of individuals through time. Killer whales are extremely long-lived, and may have the longest documented post-reproductive lifespan of any mammal, including humans. We found no strong support for either of the adaptive hypotheses of menopause; there was little support for the presence of post-reproductive females benefitting their daughter's reproductive performance (interbirth interval and reproductive lifespan of daughters), or the number of mature recruits to the population. Oldest mothers (> 35) did appear to have a small positive impact on calf survival, suggesting that females may gain experience with age. There was mixed support for the grandmother hypothesis – grandoffspring survival probabilities were not influenced by living grandmothers, but grandmothers may positively influence survival of juveniles at a critical life stage.

Conclusion

Although existing data do not allow us to examine evolutionary tradeoffs between survival and reproduction for this species, we were able to examine the effect of maternal age on offspring survival. Our results are consistent with similar studies of other mammals – oldest mothers appear to be better mothers, producing calves with higher survival rates. Studies of juvenile survival in humans have reported positive benefits of grandmothers on newly weaned infants; our results indicate that 3-year old killer whales may experience a positive benefit from helpful grandmothers. While our research provides little support for menopause evolving to provide fitness benefits to mothers or grandmothers, our work supports previous research showing that menopause and long post-reproductive lifespans are not a human phenomenon.     

Variation of carbon age of fine roots in boreal forests determined from 14C measurements

Background and aims

The main objectives of this study were to determine how the carbon age of fine root cellulose varies between stands, tree species, root diameter and soil depth. In addition, we also compared the carbon age of fine roots from soil cores of this study with reported values from the roots of the same diameter classes of ingrowth cores on the same sites.

Methods

We used natural abundance of ¹⁴C to estimate root carbon age in four boreal Norway spruce and Scots pine stands in Finland and Estonia.

Results

Age of fine root carbon was older in 1.5–2 mm diameter fine roots than in fine roots with <0.5 mm diameter, and tended to be older in mineral soil than in organic soil. Fine root carbon was older in the less fertile Finnish spruce stands (11–12 years) than in the more fertile Estonian stand (3 and 8 years), implying that roots may live longer in less fertile soil. We further observed that on one of our sites carbon in live fine roots with the 1.5–2 mm diameter was of similar C age (7–12 years) than in the ingrowth core roots despite the reported root age in the ingrowth cores – being not older than 2 years.

Conclusions

From this result, we conclude that new live roots may in some cases use old carbon reserves for their cellulose formation. Future research should be oriented towards improving our understanding of possible internal redistribution and uptake of C in trees.     

Risk Factors for Late-Life Cognitive Decline and Variation with Age and Sex in the Sydney Memory and Ageing Study

Introduction

An aging population brings increasing burdens and costs to individuals and society arising from late-life cognitive decline, the causes of which are unclear. We aimed to identify factors predicting late-life cognitive decline.

Methods

Participants were 889 community-dwelling 70–90-year-olds from the Sydney Memory and Ageing Study with comprehensive neuropsychological assessments at baseline and a 2-year follow-up and initially without dementia. Cognitive decline was considered as incident mild cognitive impairment (MCI) or dementia, as well as decreases in attention/processing speed, executive function, memory, and global cognition. Associations with baseline demographic, lifestyle, health and medical factors were determined.

Results

All cognitive measures showed decline and 14% of participants developed incident MCI or dementia. Across all participants, risk factors for decline included older age and poorer smelling ability most prominently, but also more education, history of depression, being male, higher homocysteine, coronary artery disease, arthritis, low health status, and stroke. Protective factors included marriage, kidney disease, and antidepressant use. For some of these factors the association varied with age or differed between men and women. Additional risk and protective factors that were strictly age- and/or sex-dependent were also identified. We found salient population attributable risks (8.7–49.5%) for older age, being male or unmarried, poor smelling ability, coronary artery disease, arthritis, stroke, and high homocysteine.

Discussion

Preventing or treating conditions typically associated with aging might reduce population-wide late-life cognitive decline. Interventions tailored to particular age and sex groups may offer further benefits.     

Multi factorial interactions in the pathogenesis pathway of Alzheimer’s disease: a new risk charts for prevention of dementia

Background

The population longitudinal study named “The Conselice Study” has been the focus of the present investigation. 65 years old or older participants of this population study on brain aging were followed up for 5 years: 937 subjects completed the follow-up. Relationships of 46 genetic, phenotypic, clinical and nutritional factors on incident cognitive decline and incident dementia cases were investigated.

Results

A new statistical approach, called the Auto Contractive Map (AutoCM) was applied to find relationship between variables and a possible hierarchy in the relevance of each variable with incident dementia. This method, based on an artificial adaptive system, was able to define the association strength of each variable with all the others. Moreover, few variables resulted to be aggregation points in the variable connectivity map related to cognitive decline and dementia. Gene variants and cognate phenotypic variables showed differential degrees of relevance to brain aging and dementia. A risk map for age associated cognitive decline and dementia has been constructed and will be presented and discussed.

Conclusion

This map of variables may be use to identify subjects with increased risk of developing cognitive decline end/or dementia and provide pivotal information for early intervention protocols for prevention of dementia.

     

CD56bright cells respond to stimulation until very advanced age revealing increased expression of cellular protective proteins SIRT1, HSP70 and SOD2

Background

NK cells are cytotoxic lymphocytes of innate immunity composed of: cytotoxic CD56dim and immunoregulatory CD56bright cells. The study aimed to analyze the expression of cellular protective proteins: sirtuin 1 (SIRT1), heat shock protein 70 (HSP70) and manganese superoxide dismutase (SOD2) in CD56dim and CD56bright NK cells of the young, seniors aged under 85 (‘the old’) and seniors aged over 85 (‘the oldest’). We studied both non-stimulated NK cells and cells stimulated by IL-2, LPS or PMA with ionomycin. The expression level of proinflammatory cytokines TNF and IFN-γ was also assessed in NK cell subsets and some relationships between the studied parameters were analyzed.

Results

CD56bright cells showed sensitivity to most of the applied stimulatory agents until very advanced age in regards to the expression of SIRT1 and intracellular HSP70. On the contrary, CD56dim cells, sensitive to stimulation by most of the stimulatory agents in the young and the old, in the oldest lost this sensitivity and presented rather high, constant expression of SIRT1 and HSP70, resistant to further stimulation. With reference to SOD2 expression, CD56dim cells were insensitive to stimulation in the young, but their sensitivity increased with ageing. CD56bright cells were sensitive to most of the applied agents in the young and the old but in the oldest they responded to all of the stimulatory agents used in the study. Similarly, both NK cell subsets were sensitive to stimulation until very advanced age in regards to the expression of TNF and IFN-γ.

Conclusions

CD56bright cells maintained sensitivity to stimulation until very advanced age presenting also an increased expression of SIRT1 and HSP70. CD56dim cells showed a constantly increased expression of these cellular protective proteins in the oldest, insensitive for further stimulation. The oldest, however, did not reveal an increased level of SOD2 expression, but it was significantly elevated in both NK cell subsets after stimulation.The pattern of expression of the studied cellular protective proteins in ageing process revealed the adaptation of NK cells to stress response in the oldest seniors which might accompany the immunosenescence and contribute to the long lifespan of this group of the elderly.

     

ICDs at higher age and clinical risk factors

Background

The implantable cardioverter defibrillator (ICD) is effective in preventing sudden cardiac death. However, in elderly patients (aged 75 years or older) the role of ICDs is still not well-defined and controversial.

Methods

We retrospectively analysed all clinical and survival data of all ICD patients who were ≥75 years at the date of implantation in the Erasmus MC, Rotterdam, the Netherlands and the University Hospital, Basel, Switzerland. Kaplan-Meier survival analysis was performed, and mortality predictors were identified. Mortality of the cohort was compared with a random sample of patients aged 60–70 years originating from the same database and to an age- and sex-matched cohort of Dutch persons.

Results

The study cohort consisted of 179 patients aged 75 years or older who were implanted between February 1999 and July 2008. The median follow-up time was 2.0 (IQR 2.8) years. Survival rates after 1, 2 and 3 years were 87, 82, 75 %, respectively. Survival was similar for primary and secondary prevention. Mortality in this study population could be predicted by combining four clinical risk factors: QRS duration >120 ms, NYHA class > II, renal failure and atrial fibrillation (AF). Survival was worse compared with the group of ICD patients aged 60–70 years and to the age- and sex-matched group of elderly persons. However, survival was not significantly worse when comparing elderly ICD patients without additional risk factors to the general population.

Conclusions

Elderly patients still have an acceptable survival probability independent of prevention indication, certainly if there are no additional clinical risk factors. The presence or absence of additional clinical risk factors should be taken into account when making the decision for implantation, since they strongly correlate with survival.     

Diabetes: cost of illness in Norway

Background

Hypovitaminosis D is a common condition among elderly individuals in temperate-climate countries, with a clear seasonal variation on 25 hydroxyvitamin D levels, increasing after summer and decreasing after winter, but there are few data from sunny countries such as Brazil. Many factors can interfere on vitamin D cutaneous synthesis. We aimed at studying the 25OHD variations during winter and summer in an outdoor physically active elderly population living in São Paulo city, and analysed their determining factors.

Methods

Ninety-nine individuals (52 women and 47 men, from 55 to 83 years old) from different ethnic groups were selected from an outdoor physical activity group. Data are reported as Mean ± SD, and we used Pearson Linear Correlation, Student's t-test for non-related samples, Chi-square (χ²) test and One-way ANOVA for analysis.

Results

Mean 25OHD value for the whole group was 78.9 ± 30.9 nmol/L in the winter and 91.6 ± 31.7 nmol/L in the summer (p = 0.005). Mean winter serum 25OHD concentrations were not different between men and women (81.2 ± 30.1 nmol/L vs. 76.7 ± 31.8 nmol/L, respectively), and 19.2% of the individuals showed values < 50 nmol/L. In the summer, we noticed an increase only for men (107.6 ± 31.4 nmol/L) compared to women (76.7 ± 24.0 nmol/L), and 6.5% showed values < 50 nmol/L. A decrease in the mean PTH in the summer compared to the winter was noticed, with PTH levels showing a relationship with 25OHD concentrations only in the winter (r = -0.208, p = 0.041). White individuals showed an increase in mean serum 25OHD in the summer (p = 0.016) which was not noticed for other ethnic groups (Asians, native Brazilians and blacks). An increase in 25OHD values in the summer was observed in the age groups ranging from 51-60 and 61-70 years old (p < 0.05), but not in the age group from 71 years old on.

Conclusions

25OHD values increased during the summer in elderly residents of São Paulo, but to different extents depending on ethnicity, gender and age. This season-dependent increase was noticed only among men, white and who were in the youngest group of individuals.