Age-associated Health Research Articles

Long-term impact of self-financed rotavirus vaccines on rotavirus-associated hospitalizations and costs in the Valencia Region, Spain

BackgroundRotavirus vaccines are available in Spain from 2007. They are recommended by the Spanish Pediatric Association, but not funded by the National Health System (NHS) and its coverage rate reached 40-50%. The hospitalization rate reduction of rotavirus caused gastroenteritis (RVAGE) directly attributable to vaccination remains unclear due to the large differences described in published studies, ranging from 14 to 44.5% in children <5 years of age, even with similar vaccination coverage. These results could be partly explained by variability in hospitalization policies, different study designs and the timeframe of observation. In addition, the direct economic impact of the reduction of hospitalizations has never been estimated. Therefore, there is a need to analyze the long-term impact of rotavirus vaccines on RVAGE and all cause gastroenteritis (AGE) hospitalizations and the national health system associated costs, minimizing potential confounders or biases.MethodsA population-based, ecological study using the hospital discharge registry’s Minimum Basic Data Set (MBDS) and the vaccine register (SIV) was performed, among Valencia Region’s children <5 years old, during 2002 - 2015. RVAGE and AGE hospitalization risk was analyzed by vaccine coverage and adjusted by the total hospitalization rate for all causes to avoid external biases. The impact of AGE-associated health care utilization in prevaccine (2003–2006) versus postvaccine (2008–2014) years was also assessed.ResultsAfter vaccines licensure, the incidence of RVAGE-associated hospitalizations decreased markedly. A general vaccine coverage-related reduction in RVAGE or AGE-hospitalizations risk was observed in all age groups. Compared with unvaccinated children, RVAGE hospitalization risk decreased by 67% (95% CI: 55-67), 71% (95% CI: 58-81) and 68% (95% CI: 18-92) in children 0, 1 and 4 years of age, respectively, with a vaccination coverage between 40 and 42%. Overall, the hospital related costs were reduced around EUR 6 Mill per 105 children in 7 years.ConclusionsDespite the low-medium vaccine coverage, the introduction of rotavirus vaccines had a specific coverage-related response impact in the hospitalizations for RVAGE and AGE in children <5 years and their use substantially reduced hospital related costs. The model used reassures that the estimated impact is due to the vaccination and not to other external factors.

Assessing Health Span in Caenorhabditis elegans: Lessons From Short-Lived Mutants.

Genetic changes resulting in increased life span are often positively associated with enhanced stress resistance and somatic maintenance. A recent study found that certain long-lived Caenorhabditis elegans mutants spent a decreased proportion of total life in a healthy state compared with controls, raising concerns about how the relationship between health and longevity is assessed. We evaluated seven markers of health and two health-span models for their suitability in assessing age-associated health in invertebrates using C elegans strains not expected to outperform wild-type animals. Additionally, we used an empirical method to determine the transition point into failing health based on the greatest rate of change with age for each marker. As expected, animals with mutations causing sickness or accelerated aging had reduced health span when compared chronologically to wild-type animals. Physiological health span, the proportion of total life spent healthy, was reduced for locomotion markers in chronically ill mutants, but, surprisingly, was extended for thermotolerance. In contrast, all short-lived mutants had reduced "quality-of-life" in another model recently employed for assessing invertebrate health. Results suggest that the interpretation of physiological health span is not straightforward, possibly because it factors out time and thus does not account for the added cost of extrinsic forces on longer-lived strains.

HIV Infection Is Associated with Shortened Telomere Length in Ugandans with Suspected Tuberculosis.

IntroductionHIV infection is a risk factor for opportunistic pneumonias such as tuberculosis (TB) and for age-associated health complications. Short telomeres, markers of biological aging, are also associated with an increased risk of age-associated diseases and mortality. Our goals were to use a single cohort of HIV-infected and HIV-uninfected individuals hospitalized with pneumonia to assess whether shortened telomere length was associated with HIV infection, TB diagnosis, and 2-month mortality.MethodsThis was a sub-study of the IHOP Study, a prospective observational study. Participants consisted of 184 adults admitted to Mulago Hospital in Kampala, Uganda who underwent evaluation for suspected TB and were followed for 2 months. Standardized questionnaires were administered to collect demographic and clinical data. PBMCs were isolated and analyzed using quantitative PCR to determine telomere length. The association between HIV infection, demographic and clinical characteristics, and telomere length was assessed, as were the associations between telomere length, TB diagnosis and 2-month mortality. Variables with a P≤0.2 in bivariate analysis were included in multivariate models.ResultsNo significant demographic or clinical differences were observed between the HIV-infected and HIV-uninfected subjects. Older age (P<0.0001), male gender (P = 0.04), total pack-years smoked (P<0.001), alcohol consumption in the past year (P = 0.12), and asthma (P = 0.08) were all associated (P≤0.2) with shorter telomere length in bivariate analysis. In multivariate analysis adjusting for these five variables, HIV-positive participants had significantly shorter telomeres than HIV-negative participants (β = -0.0621, 95% CI -0.113 to -0.011, P = 0.02). Shortened telomeres were not associated with TB or short-term mortality.ConclusionsThe association between HIV infection and shorter telomeres suggests that HIV may play a role in cellular senescence and biological aging and that shorter telomeres may be involved in age-associated health complications seen in this population. The findings indicate a need to further research the impact of HIV on aging.

Human neural progenitors differentiate into astrocytes and protect motor neurons in aging rats

Age-associated health decline presents a significant challenge to healthcare, although there are few animal models that can be used to test potential treatments. Here, we show that there is a significant reduction in both spinal cord motor neurons and motor function over time in the aging rat. One explanation for this motor neuron loss could be reduced support from surrounding aging astrocytes. Indeed, we have previously shown using in vitro models that aging rat astrocytes are less supportive to rat motor neuron function and survival over time. Here, we test whether rejuvenating the astrocyte niche can improve the survival of motor neurons in an aging spinal cord. We transplanted fetal-derived human neural progenitor cells (hNPCs) into the aging rat spinal cord and found that the cells survive and differentiate into astrocytes with a much higher efficiency than when transplanted into younger animals, suggesting that the aging environment stimulates astrocyte maturation. Importantly, the engrafted astrocytes were able to protect against motor neuron loss associated with aging, although this did not result in an increase in motor function based on behavioral assays. We also transplanted hNPCs genetically modified to secrete glial cell line-derived neurotrophic factor (GDNF) into the aging rat spinal cord, as this combination of cell and protein delivery can protect motor neurons in animal models of ALS. During aging, GDNF-expressing hNPCs protected motor neurons, though to the same extent as hNPCs alone, and again had no effect on motor function. We conclude that hNPCs can survive well in the aging spinal cord, protect motor neurons and mature faster into astrocytes when compared to transplantation into the young spinal cord. While there was no functional improvement, there were no functional deficits either, further supporting a good safety profile of hNPC transplantation even into the older patient population.

Conjugated Linoleic Acid: Potential Health Benefits as a Functional Food Ingredient.

Conjugated linoleic acid (CLA) has drawn significant attention since the 1980s for its various biological activities. CLA consists mainly of two isomers, cis-9,trans-11 and trans-10,cis-12, and the mixture of these two (CLA mix or 50:50) has been approved for food as GRAS (generally recognized as safe) in the United States since 2008. Along with its original discovery as an anticancer component, CLA has been shown to prevent the development of atherosclerosis, reduce body fat while improving lean body mass, and modulate immune and/or inflammatory responses. This review summarizes the clinical trials involving CLA since 2012; additional uses of CLA for age-associated health issues are discussed; and CLA's potential health concerns, including glucose homeostasis, oxidative stress, hepatic steatosis, and milk-fat depression, are examined. With ongoing applications to food products, CLA consumption is expected to rise and close monitoring of not only its efficacy but also its known and unknown consequences are required to ensure proper applications of CLA.

Smarter every day: The deceleration of population ageing in terms of cognition

Cognitive decline correlates with age-associated health risks and has been shown to be a good predictor of future morbidity and mortality. Cognitive functioning can therefore be considered an important measure of differential ageing across cohorts and population groups. Here, we investigate if and why individuals aged 50+ born into more recent cohorts perform better in terms of cognition than their counterparts of the same age born into earlier cohorts (Flynn effect). Based on two waves of English and German survey data, we show that cognitive test scores of participants aged 50+ in the later wave are higher compared with those of participants aged 50+ in the earlier wave. The mean scores in the later wave correspond to the mean scores in the earlier wave obtained by participants who were on average 4–8years younger. The use of a repeat cross-sectional design overcomes potential bias from retest effects. We show for the first time that although compositional changes of the older population in terms of education partly explain the Flynn effect, the increasing use of modern technology (i.e., computers and mobile phones) in the first decade of the 2000s also contributes to its explanation.

Older nursesʼ experiences of providing direct care in hospital nursing units: a qualitative evidence systematic review protocol

Older nursesʼ experiences of providing direct care in hospital nursing units: a qualitative evidence systematic review protocol

Dementia and mild cognitive impairment in adults with intellectual disability: Issues of diagnosis

Individuals with intellectual disability (ID) are now living longer with the majority of individuals reaching middle and even "old age." As a consequence of this extended longevity they are vulnerable to the same age-associated health problems as elderly adults in the general population without ID. This includes dementia, a general term referring to a variety of diseases and conditions causing substantial loss of cognitive ability and functional declines; adults with Down syndrome are at especially high risk. A great deal of recent effort has focused on the very earliest detectable indicators of decline (and even prodromal stages of dementia-causing diseases). A condition called mild cognitive impairment (MCI) has been conceptually defined as a decline in functioning that is more severe than expected with typical brain aging but not severe enough to meet criteria for a diagnosis of dementia. Consensus criteria for both dementia and MCI have been developed for typically developing adults but are of limited applicability for adults with ID, given their pre-existing cognitive impairments. Early diagnosis will continue to be of growing importance, both to support symptomatic treatment and to prevent irreversible neuropathology when interventions are developed to slow or halt the progression of underlying disease. While the intellectual and developmental disabilities field has for some time recognized the need to develop best-practices for the diagnosis of MCI and dementia, there remains a pressing need for empirically based assessment methods and classification criteria.

Vascular Health Modifies Theory of Mind Performance in Older Adults

Age reductions in theory of mind (ToM) are well documented, though underlying mechanisms are poorly understood. Research suggests that traditional cognitive abilities underlie ToM in part; however, whether age-associated health modifiers also predict ToM remains unknown. We investigated the role of pulse pressure (PP), an age-related marker of vascular risk, in modifying ToM performance. Sixty-six community-dwelling older adults (65-92 years) completed a short story paradigm assessing ToM. Participants also completed measures assessing blood pressure and cognitive abilities empirically linked to ToM. We used hierarchical regression to test our prediction that high PP would adversely influence associations between ToM and cognition. Reduced ToM was associated with older age and decreased verbal memory, processing speed, and working memory; however, associations between ToM and working memory were attenuated when PP was included in the regression model. Importantly, associations between ToM, memory, and processing speed were qualified by vascular health, in that participants with elevated PP showed stronger associations between reduced ToM and lower memory/speed. This is the first study to demonstrate that vascular risk modifies the strength of associations between ToM and age-sensitive cognitive resources. Results add to current perspectives on mechanisms influencing reduced ToM in older age.

Inflammation, Aging, and Cancer: Tumoricidal Versus Tumorigenesis of Immunity

Acute inflammation is a highly regulated defense mechanism of immune system possessing two well-balanced and biologically opposing arms termed apoptosis ('Yin') and wound healing ('Yang') processes. Unresolved or chronic inflammation (oxidative stress) is perhaps the loss of balance between 'Yin' and 'Yang' that would induce co-expression of exaggerated or 'mismatched' apoptotic and wound healing factors in the microenvironment of tissues ('immune meltdown'). Unresolved inflammation could initiate the genesis of many age-associated chronic illnesses such as autoimmune and neurodegenerative diseases or tumors/cancers. In this perspective 'birds' eye' view of major interrelated co-morbidity risk factors that participate in biological shifts of growth-arresting ('tumoricidal') or growth-promoting ('tumorigenic') properties of immune cells and the genesis of chronic inflammatory diseases and cancer will be discussed. Persistent inflammation is perhaps a common denominator in the genesis of nearly all age-associated health problems or cancer. Future challenging opportunities for diagnosis, prevention, and/or therapy of chronic illnesses will require an integrated understanding and identification of developmental phases of inflammation-induced immune dysfunction and age-associated hormonal and physiological readjustments of organ systems. Designing suitable cohort studies to establish the oxido-redox status of adults may prove to be an effective strategy in assessing individual's health toward developing personal medicine for healthy aging.

Absence of the proapoptotic Bax protein extends fertility and alleviates age-related health complications in female mice

The menopausal transition in human females, which is driven by a loss of cyclic ovarian function, occurs around age 50 and is thought to underlie the emergence of an array of health problems in aging women. Although mice do not undergo a true menopause, female mice exhibit ovarian failure long before death because of chronological age and subsequently develop many of the same age-associated health complications observed in postmenopausal women. Here we show in mice that inactivation of the proapoptotic Bax gene, which sustains ovarian lifespan into advanced age, extends fertile potential and minimizes many age-related health problems, including bone and muscle loss, excess fat deposition, alopecia, cataracts, deafness, increased anxiety, and selective attention deficit. Further, ovariectomy studies show that the health benefits gained by aged females from Bax deficiency reflect a complex interplay between ovary-dependent and -independent pathways. Importantly, and contrary to popular belief, prolongation of ovarian function into advanced age by Bax deficiency did not lead to an increase in tumor incidence. Thus, the development of methods for postponing ovarian failure at menopause may represent an attractive option for improving the quality of life in aging females.

Perspectives on reproductive senescence and biological aging: studies in genetically altered follitropin receptor knockout [FORKO] mice

Increased life expectancy leads to increased age-associated health issues in both sexes. For menopausal women the most important of these appear to result from the severe estrogen deficiency caused by ovarian dysfunction. The consequences among others include hot flashes, osteoporosis, obesity, impaired memory, higher incidence of Alzheimer's disease and cardiovascular disease. Ovarian function and steroidogenesis are influenced by pituitary gonadotropins, including follicle-stimulating hormone (FSH), whose actions are mediated through ovarian receptors. This article highlights our recent data pertinent to aging as derived from a novel genetically modified animal model [the FORKO mouse ( FOllitropin Receptor Knock Out) lacking the FSH receptor. FORKO female mice experience a chronic depletion of estrogen (E2) from early development, and have phenotypes similar to aging women, with ovarian failure, obesity, skeletal changes, and ovarian tumors. A variety of findings support the conclusion that E2 deficiency in FORKO mice is responsible for their neural impairments associated with glial cell hypertrophy, region-specific brain cells loss, and abnormal behavior. Findings from mice with FSH receptor haploinsufficiency mice (‘menopausal mice’) are also shedding light on the molecular basis of menopausal conditions that include degeneration of the hippocampus. Many phenotypes noted in the null condition also occur in +/− females but in an age related manner. Thus, the FORKO mouse becomes an excellent model to investigate mechanisms underlying age-related changes especially when these events are accelerated, as in menopausal women. Opportunities abound to assess the potential benefits/adverse effects of hormone replacement regimen on various targets.

Molecular wear and tear leads to terminal marking and the unstable isoforms of aging

Our studies focus on the mechanisms of molecular wear and tear, terminal marking, protein degradation, and how these processes are altered with age. Molecular wear and tear directly links catalysis with postsynthetic terminal marking. For example, the binding of ligands and catalysis cause conformational changes that are transmitted from the catalytic center to the site of terminal marking and enhance the rates of specific covalent modifications, such as deamidation or oxidation. These oxidations or deamidations can introduce "KFERQ motifs" into proteins, which may permit them to be recognized and transported to the site(s) of complete degradation. Terminally marked proteins accumulate in aging cells and tissues and account for many of the health problems of the elderly. Two-dimensional protein fingerprinting coupled with immunostaining permits identification and characterization of these proteins. Free-radical traps or caloric restriction, which may prevent the formation or enhance the degradation of terminally marked proteins, may be useful in the prevention or treatment of age-associated health problems, including dementia.

Laboratory Medicine and the Aging Process. Joseph A. Knight. Chicago: ASCP Press, 1996, 420 pp., $45.00, ISBN 0–89189-397–0.

The lack of a clear understanding of the aging process poses a dilemma for health professionals. In the past, many chronic diseases of the elderly were simply attributed to aging per se, and little treatment was offered to correct the condition. However, new research studies have shown that, for the most part, chronic diseases of the elderly are simply age-associated (increasing with age) and therefore can be successfully treated. At issue also is a satisfactory definition of aging. Clearly, physiological age is not the same as chronological age, and many attempts to find a simple and accurate indicator of physiological age have not yielded a satisfactory result because of the tremendous heterogeneity within the elderly population. This particular book recognizes all of these factors and the focus is on age-associated diseases that result in many abnormal laboratory tests. As clearly pointed out in this book, many chronic age-associated health problems …