Effects of Physical Exercise on Markers of Cellular Immunosenescence: A Systematic Review.

Aging affects negatively the immune system, defined as immunosenescence, which increases the susceptibility of elderly persons to infection, autoimmune disease, and cancer. There are strong indications that physical exercise in elderly persons may prevent the age-related decline in immune response without significant side effects. Consequently, exercise is being considered as a safe mode of intervention to reduce immunosenescence. The aim of this review was to appraise the existing evidence regarding the impact of exercise on surface markers of cellular immunosenescence in either young and old humans or animals. PubMed and Web of Science were systematically screened, and 28 relevant articles in humans or animals were retrieved. Most of the intervention studies demonstrated that an acute bout of exercise induced increases in senescent, naïve, memory CD4+ and CD8+ T-lymphocytes and significantly elevated apoptotic lymphocytes in peripheral blood. As regards long-term effects, exercise induced increased levels of T-lymphocytes expressing CD28+ in both young and elderly subjects. Few studies found an increase in natural killer cell activity following a period of training. We can conclude that exercise has considerable effects on markers of cellular aspects of the immune system. However, very few studies have been conducted so far to investigate the effects of exercise on markers of cellular immunosenescence in elderly persons. Implications for immunosenescence need further investigation.

Discriminative power of the advanced activities of daily living (a-ADL) tool in the diagnosis of mild cognitive impairment in an older population.

BACKGROUND: Mild cognitive impairment (MCI) is characterized by subjective and objective memory impairments in the absence of manifest functional decline. Mild changes in activities of daily living (ADL) can be present and probably predict conversion to dementia. A new advanced (a)-ADL tool was developed, evaluating high-level activities and, taking each participant as their own reference, distinguishing a global Disability Index (a-ADL-DI), a Cognitive Disability Index (a-ADL-CDI), and a Physical Disability Index (a-ADL-PDI), based on the number of activities performed and the severity and causes of the functional problem. This study evaluates the discriminative validity of the a-ADL in MCI. METHOD: Based upon clinical evaluation and a set of global, cognitive, mood, and functional assessments, 150 community-dwelling participants (average age 80.3 years (SD 5; 66-91)) were included and diagnosed as (1) cognitively healthy participants (n = 50); (2) patients with a-MCI (n = 48), or (3) mild to moderate AD (n = 52). The a-ADL tool was not a part of the clinical evaluation. RESULTS: The a-ADL-DI and the a-ADL-CDI showed a sensitivity and specificity ranging from 70% to 94.2%, Positive Predictive Value ranging from 70% till 93.8%, and Negative Predictive Value from 64.4% and 93.8%, an area under the curve (AUC) ranging from 0.791 to 0.960. Functional decline related to physical deficits, as assessed by the a-ADL-PDI, did not discriminate between the different groups. CONCLUSION: The a-ADL tool has a good ability to distinguish normal and pathological cognitive aging. Its discriminative power for underlying causes of limitations may be an advantage.

Shortcomings in the application of multicolour flow cytometry in lymphocyte subsets enumeration.

The lymphoid system is composed of numerous phenotypically distinct subsets of cells, each of which has a unique role in the effectiveness of an immune response. To distinguish specifically between these subsets, it is mandatory to detect simultaneously different cell surface antigens. This became feasible by the development of multicolour flow cytometric technologies. With these techniques, researchers now have the opportunity to study individual cells in far greater detail than previously possible. However, proper data analysis, interpretation and presentation of results will require a high level of understanding of the intricacies of the technology and the inherent limitations of the acquired data. The present report is intended to contribute to the better understanding of how the flow cytometer operates. This report may help new and inexperienced users to work appropriately with the flow cytometer.

Conversion of the Mini-Mental State Examination to the International Classification of Functioning, Disability and Health terminology and scoring system.

BACKGROUND: In older patients, evaluation of the cognitive status is crucial. The Mini-Mental State Examination (MMSE) is widely used for screening of cognition, providing fairly high sensitivity, specificity and reproducibility. Recently, a consensus emerged on the necessity of an international and transparent language, as provided by the WHO's International Classification of Functioning, Disability and Health (ICF). Most assessment tools however are not in accordance with the ICF. OBJECTIVE: To reformulate the MMSE according to the ICF, both for the individual items and for the scoring system. METHOD: MMSE data (scores varying from 3 to 30/30) of (1) 217 cognitively healthy elderly, (2) 60 persons with mild cognitive impairment, (3) 60 patients with mild Alzheimer's disease (AD), and (4) 60 patients with moderate/severe AD were obtained from studies at a university hospital setting. Subjects were aged 65 years or more and recruited either through advertisement (group 1), from the geriatric day hospital (groups 2 and 3), or the geriatric ward (group 4). The allocation to the groups was done after multidisciplinary evaluation. The conversion of the MMSE to ICF-MMSE was done by content comparison and by subsequent translation of the scoring system using automatic algorithms. RESULTS: All MMSE items were converted to the corresponding ICF categories. Three ICF domains were addressed: global and specific mental functions, general tasks and demands, divided over 6 ICF categories (orientation time/place, sustaining attention, memory functions, mental functions of language, undertaking a simple task). Scores on individual items were transformed according to their relative weight on the original MMSE scale, and a total ICF-MMSE score from 0 (no problem) to 100 (complete problem) was generated. Translation was satisfying, as illustrated by a good correlation between MMSE and ICF-MMSE. The diagnostic groups were distributed over the ICF-MMSE scores as expected. For each ICF domain, ICF-MMSE subscores were higher with increasing severity in cognitive decline. There was a higher dispersion, in accordance with the more detailed scoring possibilities of the ICF-MMSE. CONCLUSIONS: It is possible to adapt the MMSE to the ICF concept. This adaptation enhances interdisciplinary communication since it provides more clarity in assessment, with better visibility of the areas covered by the instrument.

Integrating the International Classification of Functioning, Disability and Health (ICF) in the Geriatric Minimum Data Set-25 (GMDS-25) for intervention studies in older people.

OBJECTIVE: Since the number of older people is rising worldwide, there is an increasing need for a structured and integrated approach for the participation of the older person in clinical research. The introduction of a 'Geriatric Minimum Data Set' (GMDS) will allow a standardized description of the older person participating in clinical research. ICF, a universal tool for the comprehensive description of human functioning, developed by the World Health Organisation, can make a substantial contribution to the development of a GMDS. It can serve as a 'framework', including all the functional characteristics needed in research in Gerontology and Geriatrics. The objective was to integrate ICF terminology in a recently proposed GMDS-25. DESIGN: ICF is explored to determine the most relevant ICF-categories for GMDS-25. RESULTS AND CONCLUSION: Several items of the GMDS-25 can be described in terms of ICF. This description contributes to the optimal standardization of the GMDS-25.

Relating the MNA Mobility Single Item to Usual Walking Speed in Hospitalized and Community-Dwelling Geriatric Patients.

Usual walking speed (WS) is a relatively easy and reproducible tool for detecting mobility impairment. For some reasons, however, geriatric patients might not be able to perform walking tests. Therefore, a subjective assessment could be an alternative method to screen for mobility impairment. In the present paper, we explore the use of the mobility item from the Mini Nutritional Assessment-short form (MNA-sf) to assess mobility and its congruence with walking speed in hospitalized and ambulatory patients. We analyzed retrospective data from 357 patients and found a highly significant correlation between WS and the MNA-sf mobility item. After dichotomization of the MNA-sf mobility score (mobility impairment ≤1 and no impairment >1), AUC for ROC curves showed that the mobility item derived from the MNA-sf reflects fairly well the mobility of geriatric hospitalized patients (AUC = 0.773), while it performs better in ambulatory patients (AUC = 0.838).

Force-time characteristics during sustained maximal handgrip effort according to age and clinical condition.

BACKGROUND: Muscle fatigue, a prominent symptom in older patients, can be assessed by sustained maximal handgrip testing. The force decline during sustained maximal contraction is described for young adults, but data for elderly persons are scarce. The aim of this study was to investigate force-time characteristics during a sustained maximal handgrip effort according to age and clinical condition. METHODS AND MATERIALS: Force-time data were continuously recorded during sustained maximal grip effort in 91 elderly patients (aged 83±5years), 100 elderly controls (aged 74±5years) and 100 young controls (aged 23±3years). The force-time curve was divided in 4 parts per 25% strength drop observed. Time (representing fatigue resistance (FR)) was measured during which grip strength (GS) dropped to 75% (FR75), 50% (FR50), 25% (FR25) of its maximum and to exhaustion (FRexhaustion). Grip work ((GW), the area under the force-time curve) was measured for the 4 parts as well as for the first 20 and 30s of the fatigue protocol test. Strength decay (GWdecay), defined as the difference between the area under the curve (% GW) and a theoretical maximal area under the curve (assuming there's no strength drop), was also studied. In the elderly participants, relationships (controlling for age and sex) of GS, FR and GW with circulating IL-6 and TNF-α were analyzed. RESULTS: FRexhaustion was similar for all groups, whereas the duration of each of the 4 parts was significantly different between the 3 groups. FR75 was shortest in old patients (p=0.004), FR75-50 was almost twice as long in old community-dwelling compared to old patients and young controls (p<0.001). This contrast was inverted for FR50-25 which was significantly shorter in old community-dwelling compared to the other groups (p=0.013). FR25-exhaustionwas significantly longer in young controls compared to the groups of older participants (p=0.017). Old patients showed lower GW for the first 2 parts compared to old community-dwelling and young controls. Also, GWdecay values during the first 20 and 30s were significantly higher in old patients compared to old community-dwelling and young controls (both p<0.001). IL-6 was significantly related to lower GSmax, FR75, FR50, FR25, FRexhaustion, GW75, GW50 and GW75-50. CONCLUSION: This is the first study reporting differences in strength decay during a sustained maximal handgrip effort according to age and clinical condition. Old patients showed a particularly rapid decline in GW during the first part of sustained handgrip. GW was also significantly related to circulating IL-6. Future studies should confirm whether a shorter FR test protocol (i.e. until FR75) but using a continuous registration of the strength decay could be more informative in a clinical setting compared to the classical FR test (measuring only FR50).

The effect of aging and inflammation on heat shock protein 27 in human monocytes and lymphocytes.

Heat shock proteins (Hsp) are highly conserved proteins and their synthesis is ubiquitous in virtually every species in which they have been sought. In the present study we have investigated the effect of age and inflammation on the induction of Hsp27 in human peripheral blood mononuclear cells, using flow cytometry. Sixty-six healthy control subjects or patients suffering from inflammation participated in the study. In both heat shocked (HS) and non-HS conditions, the percentage of Hsp27 producing lymphocytes as well as the intensity of Hsp27 in lymphocytes and monocytes were negatively influenced by age. The basal levels and also the levels of Hsp27 production after HS were higher for monocytes compared to lymphocytes. In addition, we found that HS resulted in a small but significant increase in the levels of Hsp27 in lymphocytes whereas a significant decrease in Hsp27 was noticed for monocytes. In conclusion, results presented herein provide evidence in support of an age-related decrease in the level of Hsp27, which disappeared in the presence of inflammation. Several relationships between the circulating levels of CRP, IL-6 and TNF-alpha with the various Hsp27 determinations were observed, indicating that cytokines are able to influence the production of Hsp27.

Variations in the stromal cell population of human bone marrow during aging.

Age-related variations in the stromal cell population of human bone marrow were studied by means of a cloning assay. It was found that these cells are heterogeneous both in division capacity and in morphology. Fibroblast-like progenitor cells could be distinguished from epithelial-like cells, having only a very limited division potential. A significant inverse correlation between the donor age and the number of progenitor cells could be demonstrated. This loss of progenitor cells during aging was compensated by an increase in the number of epithelial-like cells.

In vitro aging of human bone marrow derived stromal cells.

We have studied the in vitro cellular aging process in human bone marrow derived stromal cells. Two cell types, here called type I and type II, can be distinguished in the primary cell population. During subcultivation, resulting in aging in vitro, the type I cells gradually disappear, whereas the type II cells form an increasing fraction of the population. This observation is confirmed by cloning experiments, revealing that type I cells act as progenitor cells, giving rise to non-dividing type II cells. These results are best explained by the terminal differentiation theory as proposed by Martin et al.

Similarity between in vitro and in vivo cellular aging.

In vivo and in vitro cellular aging were compared by determining the division capacity of individual, cloned cells of (1) the primary stromal population of human bone marrow, obtained from donors of various ages, and (2) the population at various passage levels of an in vitro subcultivated culture of the same origin. We find a strong similarity between the two series of data. This observation provides a further argument that cellular aging in vitro represents a biologically relevant phenomenon.

Pseudomyxoma peritonei. Report of a case with extraperitoneal metastasis and invasion of the spleen.

The findings in a patient with pseudomyxoma peritonei, probably of appendicular origin, are reported. As a rule, pseudomyxoma peritonei remains limited to the peritoneal cavity, but in this case, dissemination occurred to the right pleural cavity and to the pericardium. In addition, invasion of the spleen (to our knowledge, nor previously described) was noted.

The association of bronchiolitis obliterans organizing pneumonia, systemic lupus erythematosus, and Hunner's cystitis.

An 83-year-old woman with histologically confirmed Hunner's cystitis presented with persistent fever, progressive dyspnea, and pulmonary patchy infiltrates. A transbronchial biopsy specimen revealed bronchiolitis obliterans organizing pneumonia. She progressively had development of renal insufficiency, due to systemic lupus erythematosus, proved by renal biopsy specimen. She recovered under corticosteroid treatment, but irreversible renal failure made long-term hemodialysis necessary.

The 6-minute walk as an appropriate exercise test in elderly patients with chronic heart failure.

BACKGROUND: The value of the 6-minute walk in a population of elderly patients with chronic heart failure (CHF) has not yet been established, as it has been in a younger population. METHODS: In a prospective trial, 2 exercise tests were compared: the 6-minute walk (6 MW) and a treadmill test with progressive increments in workload. 37 patients (mean age 81.3, SD 5.6 years): 11 untrained controls, 16 patients with New York Heart Association (NYHA) class II and 10 patients with NYHA class III participated. The main outcome measures were the distance walked in 6 minutes, the symptomatic VO2max in the progressive treadmill test and the degree of CHF as scored by the NYHA classification and the Boston Study Group (BSG) score. RESULTS: For both the 6 MW and the treadmill test there was a significant difference in distance between NYHA class II and III patients (p < .001), between the controls and NYHA class III patients (p < .001), but not between the controls and NYHA class II patients. The distance walked in the 6 MW was well correlated with the distance walked in the treadmill test (p < .001). Eight participants (22%), however, were unable to perform this treadmill test and 6 participants (17%) covered very low distances compared to the 6 MW. The VO2max was lower in NYHA class III than in class II patients (p = .032). NYHA classification and BSG score correlated reasonably well. CONCLUSION: A treadmill exercise test with VO2max measurement in elderly patients with CHF is difficult to accomplish. On the contrary, the 6 MW gives a good impression of the remaining exercise capacity. It is well correlated with the treadmill test. The 6 MW is well tolerated by elderly patients and differentiates between NYHA classes II and III. Untrained controls could not be differentiated from NYHA class II patients.

Risk of malnutrition in retirement homes elderly persons measured by the "mini-nutritional assessment".

BACKGROUND: The combined influence of age-associated factors such as general health, degree of dependency, diminished odor perception, and poor oral health on the risk for malnutrition was explored. METHODS: A total of 81 persons living in retirement homes took part in the study (mean age 83.4 years, SD = 6.6, range 61-98). The Mini-Nutritional Assessment (MNA) was used to evaluate the risk of malnutrition. Odor perception was measured by the detection threshold for isoamylacetate. The number of drugs taken by each person was counted. General health status was determined by the Medical Outcome Study (MOS) scores. Oral examinations were carried out to count the number of natural teeth and type of dentures. RESULTS: On average, women had slightly, but significantly, lower MNA scores than men (respectively, 23.4, SD = 2.8; and 24.6, SD = 2.6; p = .048). The correlations between age and MNA score and between odor perception and MNA score were not significant. Significant correlations were found between age and number of natural teeth (r = -.26, p = .001) and between MNA score and number of natural teeth (r = .27, p = .001). The mean MNA score of complete denture wearers (22.8, SD = 2.9) was significantly lower than that of partial denture wearers (25.8, SD = 2.9; p = .0005). The total MOS and MNA scores were not correlated, but a significant correlation was found with the subscales mental functioning (r = .29, p = .003), social functioning (r = . 19, p = .045), and perceived health (r = .19, p = .047). No relation was found between the activities of daily living (ADL) and MNA scores. A significant negative correlation was observed between number of drugs taken and the MNA score (r = -.34, p = .001). When participants without risk of malnutrition (MNA > or = 24) were compared with those at risk (MNA = 17-23.5), again, the number of drugs taken was significantly different (on average, respectively, 4.5, SD = 2.9; and 7.0, SD = 2.6; p < .0005). Using multiple regression to test the separate effects of the different independent variables, the number of drugs taken showed a significant negative regression coefficient (beta = -.31, p = .008), as did the mental health score (beta = .27, p =.02), giving a total R2 = .32. The other parameters did not contribute significantly. CONCLUSION: Among the elderly in retirement homes, the health state (as measured by the MOS subscale mental health and by the medication use) appears to be the most clinically relevant parameter to explain the risk for malnutrition. Loss of natural teeth and perceived health are less independently contributing, whereas no contribution derives from decline of odor perception, degree of dependency, and age itself.

Food odor thresholds in relation to age, nutritional, and health status.

Odor perception plays an important role in nutrition. In the present study, the effect of aging and health status on detection of food odors is shown and interrelations with nutritional status are explored. We have tested 26 healthy young (20-25 yrs) and 23 elderly (61-74 yrs) subjects who were screened according to the SENIEUR protocol. Anthropometric measures and blood samples provided 20 parameters of nutritional status. A validated measurement procedure under forced choice conditions was used to quantify the detection thresholds of two food odors of which one had a trigeminal effect and the other mainly had an olfactory effect. There is a significant declining sensitivity for both odors. Our observations indicate that a relation between nutrition and odor perception in the elderly population exists. Whether olfactory deficits cause or are caused by increased nutritional risk deserves further study.

Drug-induced orthostatic hypotension in the elderly: avoiding its onset.

The prevalence of orthostatic hypotension in the elderly is reported to be 5 to 33%. This high prevalence contributes to the risk of syncope and falls in old age. Drugs are a major cause of postural hypotension. Changes in pharmacokinetics and pharmacodynamics occur with aging in relation to many drugs, resulting in delayed elimination and increased bioavailability. Therefore, drugs with an antihypertensive action (diuretics, calcium antagonists, beta-blockers, ACE inhibitors, alpha 1-blockers, and centrally acting antihypertensives) have a more pronounced effect in the elderly. Nitrates, antiparkinsonian drugs, antidepressants and antipsychotics all cause hypotension as a known adverse effect. When assessing orthostatic hypotension in the elderly, drug treatment should always be reviewed. Whenever possible, antihypertensive drugs should be discontinued, and the dosages of essential drugs should be reduced.

Drug-induced orthostatic hypotension in older patients.

Orthostatic hypotension occurs in 10 to 30% of the elderly. In several studies it has been linked to recurrent falls and syncope. Generally, it has multiple causes, of which autonomic dysfunction plays an important role in elderly people. Very often orthostatic hypotension is induced by the use of drugs. In other cases, it is already present subclinically, and is worsened by the use of drugs to become symptomatic. For most drugs, changing pharmacokinetics result in a delayed elimination and/or in a greater bioavailability in the elderly. This results in a more pronounced effect for drugs with a desired hypotensive action [e.g. diuretics, calcium channel blockers, beta-blockers, angiotensin converting enzyme (ACE) inhibitors]. For those drugs in which hypotension is a known but unwanted adverse effect (e.g. nitrates, anti-Parkinsonian drugs, antidepressants, antipsychotics), responses will be greater in the elderly and orthostatic hypotension will occur more frequently. For elderly people, doses have to be reduced and/or the dose intervals prolonged in order to avoid such adverse reactions.

Variation in nutrient intake with dental status, age and odour perception.

OBJECTIVES: Since the proportion of elderly people with an insufficient intake of nutrients is high and many of the elderly have poor odour perception or poor dental state, in this study, the relation between age, odour perception, dental state and nutrient intake is explored. DESIGN: Single centre cross sectional study. SETTING: Independently living elderly were tested at their homes in 4 locations in Belgium, ranging in ages 60-90 y. SUBJECTS: 200 elderly participated in a 7 d food record study, resulting in 119 complete records. INTERVENTIONS: Food quantities were converted to nutrient intake levels. For all people, odour detection threshold was determined of isoamylacetate and dental status was noted. Path analysis was used and the separate effects of age, dental state, odour perception and gender were tested on macronutrient intake and micronutrient intake respectively. MAIN OUTCOME MEASURES: For all nutrients, no significant correlation was observed between nutrient intake and odour perception, except for energy, water, Fe and niacin (P < 0.05). A significant separate effect of odour perception was observed for water intake (CR = 2.09). Significant separate effects of dental state were observed for animal protein (CR = 2.29), niacine (CR = 2.04) and mono-unsaturated fats (CR = 2.32). CONCLUSIONS: Although odour perception and dental state can not fully explain variability in nutrient intake, our results show that people with poor odour perception have lower nutrient intake levels than people with good odour perception. Dental state may not be a direct cause of poor nutrition but a contribution factor in those elderly who have other risk factors.

Benzodiazepine use among elderly patients presenting at the emergency room.

This study evaluated the prevalence of benzodiazepine intake by elderly patients presenting at the emergency room of a university hospital. Of 388 patients, 42.5% used one or more benzodiazepine (BZD) drugs in the week prior to admission. There were significantly more women among the BZD users (P < 0.05). Mean duration of intake was long (62 months), but daily dosage was adjusted to age. Of the BZD using patients, 27% took a BZD with long elimination half life. No relationship was found between the BZD intake and the occurrence of falls. Fallers were significantly older (P = 0.019) and were more often women (P = 0.046).