Age-associated Health Research Articles

A NEW ROLE FOR KYNURENINE METABOLISM IN THE AGE-ASSOCIATED DECLINE OF THE BACTERIAL IMMUNE RESPONSE

Abstract Tryptophan metabolism through the kynurenine pathway becomes dysregulated during normal aging and is implicated in age-associate disease, including chronic inflammation, atherosclerosis, neurodegeneration, and cancer. Kynurenine pathway enzymes and metabolites influence a range of molecular processes critical to healthy aging, including regulation of inflammatory and immune responses. Kynurenine metabolism is active in immune cells and activated in response to proinflammatory cytokine signaling. We previously determined that elevating physiological levels of the kynurenine pathway metabolite 3-hydroxyanthranilic acid (3HAA) via either direct supplementation or inhibition of the enzyme that degrades 3HAA, 3HAA dioxygenase (HAAO), extends lifespan and delays age-associated health decline in Caenorhabditis elegans. Published work suggests that 3HAA is anti-inflammatory in mammals, for example by reducing the ratio of activated to regulatory T cells and inhibiting pathological activation of macrophages. In recent work, we find that elevating physiological 3HAA can beneficially enhance the immune response of C. elegans to bacterial pathogens during aging. 3HAA is sufficient to kill bacterial and inhibit bacterial growth in culture. When HAAO is inhibited in C. elegans, 3HAA accumulates in lysosome related organelles (LROs) in the intestinal cells, the same subcellular compartment that contains engulfed bacteria. LROs are a cellular repository for both iron and zinc, and we further find that iron chelation or zinc supplementation dramatically enhances the bactericidal properties of 3HAA. Here we present a mechanistic model in which age-dependent accumulation of 3HAA in intestinal LROs combines with zinc to enhance bacterial resistance with age in C. elegans.

On the benefits of the tryptophan metabolite 3-hydroxyanthranilic acid in Caenorhabditis elegans and mouse aging

Tryptophan metabolism through the kynurenine pathway influences molecular processes critical to healthy aging including immune signaling, redox homeostasis, and energy production. Aberrant kynurenine metabolism occurs during normal aging and is implicated in many age-associated pathologies including chronic inflammation, atherosclerosis, neurodegeneration, and cancer. We and others previously identified three kynurenine pathway genes—tdo-2, kynu-1, and acsd-1—for which decreasing expression extends lifespan in invertebrates. Here we report that knockdown of haao-1, a fourth gene encoding the enzyme 3-hydroxyanthranilic acid (3HAA) dioxygenase (HAAO), extends lifespan by ~30% and delays age-associated health decline in Caenorhabditis elegans. Lifespan extension is mediated by increased physiological levels of the HAAO substrate 3HAA. 3HAA increases oxidative stress resistance and activates the Nrf2/SKN-1 oxidative stress response. In pilot studies, female Haao knockout mice or aging wild type male mice fed 3HAA supplemented diet were also long-lived. HAAO and 3HAA represent potential therapeutic targets for aging and age-associated disease.

Frailty and overall survival in metastatic castration-resistant prostate cancer treated with abiraterone or enzalutamide.

71 Background: Abiraterone (ABI) and Enzalutamide (ENZ) are both treatment options for metastatic castration-resistant prostate cancer (mCRPC). However, both drugs have differing pharmacodynamics, so patient factors may selectively impact drug efficacy. Age-associated health deficits make older adults variably susceptible to disease under a syndrome termed frailty. The average age of initial prostate cancer diagnosis is age 66, and the average time to mCRPC progression is 11.7 years. Thus, frailty is an important patient factor to consider in mCRPC, and it may play a role in personalizing drug selection. Methods: Patients treated with ABI or ENZ for mCRPC from September 2014 to June 2017 were identified in the VA and followed until April 2020. Frailty was assessed using the VA frailty index, which looks at ICD-10, CPT, and HCPCS codes to assign a standardized frailty score between 0-1. Patients were categorized as frail if their VA-FI scores were > 0.2. The primary outcome was overall survival (OS) between the ABI and ENZ treatment groups. Cox regression models included age, race, body mass index, PSA, and total Charlson Comorbidity Index (CCI). For frail patients, a propensity score-matched cohort was also created by matching age, race, CCI, and total VA-FI between ABI and ENZ treatment groups. Results: Of the 5,822 patients identified, 57% were initially treated with ABI and 43% with ENZ. The ABI group had a lower mean VA-FI score of 0.192 compared to the ENZ group of 0.203 (p=0.004). Frail patients were older: mean 74.9 years vs. 76.1 years for non-frail (p<0.001). Frail patients had shorter survival than non-frail (18.5 vs. 26.6 months, p<0.001). In multivariable models, frailty was associated with increased risk of death (aHR 1.32, 95% CI 1.23-1.42). Among non-frail patients (n=3508, 60.3%), there was no significant difference in OS between ABI and ENZ treatment. Among frail patients (n=2314, 39.7%), patients treated with ENZ had a 3.5 month greater median OS than ABI (20.7 vs. 17.2 months, p = 0.0003 by log-rank). In frail patients, ENZ was associated with reduced risk of death (aHR 0.85, 95% CI 0.78-0.94). In a propensity matched cohort of 2070 patients, the enzalutamide treatment group had a 3.2 months greater median OS in the enzalutamide group than the abiraterone group (24.1 months vs. 20.9 months, p < 0.001). Conclusions: ENZ was associated with improved OS compared to ABI among frail veterans, but not among non-frail veterans. The improved survival remained significant in a propensity score-matched cohort and models including important covariates. Further assessment of the value of frailty in personalizing drug treatment is warranted to improve the care of older adults with advanced prostate cancer.

5-Year Observation Period of Quality of Life After Cochlear Implantation.

Only few studies assessed health-related quality of life (HRQoL) in cochlear implant (CI) patients for a period of more than 2 years. Some of these studies indicated that HRQoL might decrease after that period. The goal of our study was to see whether HRQoL indeed decreases or remains stable beyond 2 years after implant activation. Twenty-five adults (11 women, 14 men; mean age at implantation: 60 ± 19 yr) with a unilateral CI for profound hearing loss were administered two questionnaires: the Nimjegen Cochlear Implant Questionnaire and the Health Utility Index 3 (HUI 3). The Nimjegen Cochlear Implant Questionnaire total score and the HUI single-attribute utility score of Hearing are measures of hearing-specific HRQoL, whereas the HUI multiattribute utility score is a measure of generic HRQoL. The questionnaires were administered before cochlear implantation and 1, 2, and 5 years after implant activation. Hearing-specific HRQoL was significantly improved at 1 year after implant activation and did not significantly change thereafter. Generic HRQoL also showed significant improvement at 1 year after implant activation, but deteriorated to a clinically relevant degree thereafter. The significant improvement of hearing-specific HRQoL obtained from cochlear implantation was fully maintained for up to 5 years after implantation. Generic HRQoL of our CI patients, however, fluctuated over time. The decrease of generic HRQoL is supposed to reflect general age-associated health declines.

EXTENDING A HEALTHY LIFESPAN WITH 3-HYDROXYANTHRANILIC ACID

Abstract Metabolism of tryptophan by the kynurenine pathway is increasingly linked to aging. Kynurenine pathway enzymes and metabolites influence a range of molecular processes critical to healthy aging, including regulation of inflammatory and immune responses, cellular redox homeostasis, and energy production. Aberrant kynurenine metabolism occurs during normal aging and is implicated in many age-associated pathologies including chronic inflammation, atherosclerosis, neurodegeneration, and cancer. We and others previously identified three kynurenine pathway genes—kynu-1, tdo-2, and acsd-1—for which decreasing expression extends lifespan in invertebrates. More recently we discovered that knockdown of haao-1, a fourth kynurenine pathway gene encoding the enzyme 3-hydroxyanthranilic acid dioxygenase (HAAO), extends lifespan by ~30% and delays age-associated health decline in Caenorhabditis elegans. Lifespan extension is mediated by increased physiological levels of the HAAO substrate 3-hydroxyanthranilic acid (3HAA). Aging mice fed a diet supplemented with 3HAA are similarly long-lived. The mechanism of action liking 3HAA to aging is complex and partially overlaps with multiple pathways previously implicated in aging. We recently identified activation of the Nrf2/SKN-1 oxidative stress response and alterations to iron homeostasis as key players in the benefits 3HAA. Ongoing work explores the relationship between 3HAA, Nrf2/SKN-1, and iron in C. elegans and mammalian aging, age-associated immune decline, and cancer. This works provides a foundation for detailed examination of the molecular mechanisms underlying the benefits of 3HAA, and how these mechanisms interact with other anti-aging interventions. We anticipate that these findings will bolster growing interest in developing pharmacological strategies to target tryptophan metabolism to improve health aging.

Epigenetic alterations-The silent indicator for early aging and age-associated health-risks.

Aging is the process of gradual physiological deterioration till death and this process perpetually reduce the functionality of an individual. To address the rationale and provide geriatric care, the constant target of geroscience is to identify reliable biomarkers for aging. Over the past decades, diversified advancements in epigenetic studies crescively support the fact that the accumulation of epigenetic changes accompanies the process of aging. A growing number of studies have suggested that alterations occur through three fundamental mechanisms like methylation of DNA, histone protein modification, and production of non-coding microRNAs. Each of these changes occurs silently and provokes alterations in the circumstantial expression of genetic material without altering the underlying gene sequences. The changes in gene expression due to epigenetic alterations are suggested to be the cause of early aging and the onset of age-related health risks. This review would attempt to give an integrated overview of epigenetic changes related to aging and age-associated health risks. This review also discussed epigenomes influencing early aging and factors modulating it. Since epigenetic changes are reversible, early identification of epigenetic markers can be a hope for future geriatric medicine. Finally, this review emphasizes the identification of blood-based epigenetic biomarkers in order to enlighten the future scope for therapeutic intervention to slow down the aging process.

Tetramethylpyrazine nitrone TBN extends the lifespan of C. elegans by activating the Nrf2/SKN-1 signaling pathway

SKN-1, the ortholog of mammalian Nrf2 proteins, is a transcription factor that plays an important role in oxidative stress resistance and longevity. Similar to other defense systems, the Nrf2-mediated stress response is compromised in aging and neurodegenerative diseases. Our previous studies demonstrated that tetramethylpyrazine nitrone (TBN), a derivative of tetramethylpyrazine armed with a potent free radical-scavenging nitrone moiety, exerted multifunctional neuroprotection in neurological and other diseases. However, the ability of TBN to extend a healthy lifespan and its underlying mechanisms of action are not yet clear. C. elegans have become a popular animal model in aging research. Herein, we demonstrate that TBN can extend the lifespan, promote age-associated health indicators, and restore mitochondrial function in C. elegans. TBN also significantly reduced ROS levels and superoxide accumulation in C. elegans. We show that TBN-mediated lifespan extension is SKN-1dependent. The present study provides valuable insights into the mechanisms by which TBN inhibits aging via the Nrf2/SKN-1 pathway in C. elegans.

Health situation of adults in Germany - Results for selected indicators from GEDA 2019/2020-EHIS.

In this article, we examine selected health indicators for the adult population aged 18 years and older in Germany (n=22,708) from the German Health Update (GEDA 2019/2020-EHIS) conducted between April 2019 and September 2020. These indicators include those of self-assessed health and depressive symptoms as well as chronic physical diseases and conditions. In young adulthood (18 to 44 years), over 80% of participants report good or very good subjective health. During this phase of life, most chronic diseases and conditions are rare, although allergies are frequent, and bronchial asthma and depressive symptoms are not uncommon. From mid adulthood (45 years and older), there is a gradual increase in the prevalence of chronic diseases such as cardiovascular disease, diabetes, chronic obstructive pulmonary disease and osteoarthritis. Over 60% of older adults (65 years and older) report a chronic disease or long-term health problem, while only half continue to report good or very good subjective health. During this stage of life, allergies and depressive symptoms become less prevalent. For some diseases, there are also differences according to gender and level of education. This article demonstrates the high public health relevance of age-associated chronic physical diseases and health related limitations in everyday life in an ageing society as well as the need to provide care for certain health conditions already in young adulthood.

Promoting neuroplasticity and neuropsychological functioning in frailty through an app-based sensorimotor training: study protocol for a randomized trial

BackgroundFrailty is characterized by an age-related decline in multiple physiological systems, leading to a high vulnerability to stressors, adverse health outcomes, and low quality of life. Neuroscientific models of pathological aging emphasize the loss of sensorimotor stimulation and reduced neuromodulatory capacities as core processes in age-related cognitive and bodily decline, which may be associated with maladaptive plastic changes in the brain. We plan to increase sensorimotor stimulation in frail persons through a newly developed app-based training program and link the training trials to biological and psychological correlates of age-associated vulnerability and health indices.MethodsWe will conduct a randomized trial, applying an app-based sensorimotor home training (N = 30) in people suffering from frailty. An app-based relaxation training will serve as an active control condition (N = 30). Both interventions will last for 90 days each. The sensorimotor training includes unimodal and multimodal sensory discrimination tasks in the visual, auditory, and tactile domain, as well as sensorimotor precision tasks. The tasks will be implemented using an adaptive training algorithm and enriched with motivational components embedded in a virtual training environment. We expect a pre-post reduction of frailty status and associated functional decline related to refinement of representational maps within the sensorimotor system and improved sensorimotor function such as extremity function. Secondary analyses will study the influence of BDNF genotype as moderating variable. Additional outcomes will include measures of perceptual and cognitive functioning, quality of life as well as BDNF serum levels. Measurements will take place before training (baseline), after 60 days (assessment 1), and at the end of the training after 90 days (assessment 2).DiscussionIn our randomized trial, we aim to characterize a multidimensional concept of frailty and to target maladaptive behaviors and neuroplasticity using an app-based sensorimotor training. This type of intervention might provide further knowledge and new possibilities for preventing decline and preserving function in older adults.Trial registrationClinicalTrials.gov NCT03666039. Registered 11 September 2018 – Retrospectively registered.Protocol version: Version 4 revised (issue date: 19 May 2021).

Cocoa improves age-associated health and extends lifespan in C. elegans

BACKGROUND: Cocoa, one of the richest dietary sources of polyphenols has been studied for its health promoting effects, but how long-term consumption of cocoa affects age-associated health and lifespan is not well defined. OBJECTIVE: The objective of this study was to determine the effects of long-term cocoa consumption on age-associated health and lifespan in C. elegans METHODS: The standard E. coli OP50 diet of wild type C. elegans was supplemented with cocoa powder starting from L1 stage until they die. Body length and area were measured as indicators of worm nutrition. Age associated health was determined at different stages of life as day 4, day 8 and day 12 using worm locomotion, thermotolerance, cognition and mitochondrial function. In addition, lifespan was evaluated. RESULTS: Cocoa improved age-associated decline in neuromuscular function. Both mean and median lifespan were extended by cocoa supplementation. However, maximum lifespan was not affected. Cocoa showed beneficial effects on thermotolerance at all ages (more prominent effects at young (day 4) and middle (day 8) age). Further, consumption of cocoa improved age-related learning deficits, short-term memory loss and mitochondrial dysfunction. CONCLUSIONS: Long-term cocoa consumption seemed to improve age-associated health and extends lifespan in C. elegans

Advancing health literacy measurement in old age.

Health literacy is described as a domain of competence across the life-span, gaining particular prominence in light of age-associated health restrictions. However, no specific measurement approach has been proposed for old age. The aim of this study is to augment the existing HLS-EU-Q16 scale (16 items) by items sensitive to age-specific aspects of health literacy to ensure validity and reliability for use in old age. In a first step, the HLS-EU-Q16 was administered in a sample of 463 individuals aged 72 - 92 years. Psychometric properties were evaluated using confirmatory factor analysis and item-response-theory item fit statistics. Scale reliability was found to be poor in this population segment. In a second step, age-specific items were developed based on qualitative in-depth interviews with older persons. In a third step, we tested if the additional set of age-specific items was able to enhance a valid and reliable measurement of health literacy in a second sample of older adults (N = 107, 49 - 91 years). With the inclusion of an eight-item add-on, it was possible to measure health literacy in old and very old age with both high validity and satisfying precision (reliability = 0.80). The study contributes to a population-specific measurement of health literacy.

Early Exposure is Necessary for the Lifespan Extension Effects of Cocoa in C. elegans.

Background:We previously showed that cocoa, a rich source of polyphenols improved the age-associated health and extended the lifespan in C. elegans when supplemented starting from L1 stage.Aim:In this study, we aimed to find out the effects of timing of cocoa exposure on longevity improving effects and the mechanisms and pathways involved in lifespan extension in C. elegans.Methods:The standard E. coli OP50 diet of wild type C. elegans was supplemented with cocoa powder starting from different larval stages (L1, L2, L3, and L4) till the death, from L1 to adult day 1 and from adult day 1 till the death. For mechanistic studies, different mutant strains of C. elegans were supplemented with cocoa starting from L1 stage till the death. Survival curves were plotted, and mean lifespan was reported.Results:Cocoa exposure starting from L1 stage till the death and till adult day 1 significantly extended the lifespan of worms. However, cocoa supplementation at other larval stages as well as at adulthood could not extend the lifespan, instead the lifespan was significantly reduced. Cocoa could not extend the lifespan of daf-16, daf-2, sir-2.1, and clk-1 mutants.Conclusion:Early-start supplementation is essential for cocoa-mediated lifespan extension which is dependent on insulin/IGF-1 signaling pathway and mitochondrial respiration.

A CLINICAL STUDY TO EVALUATE THE RASAYANA EFFECT OF ASTHISHRINKHALAGHRITA IN JARA

Modern medicine has made a great deal of progress in understanding the aging process and in controlling age-associated health issues. The problems of Aged were neglected by Ayurvedic science and recently there started new advancements in this branch of Ayurveda which is insufficient for the current needs. This had led to lack of active longevity with more disability and dependency. Thus, this study was taken up to evaluate the Rasayana (Anti- ageing) effect of Asthishrinkhalaghrita in Jara janya vyadhi (Diseases due to senility). Methods: In present study, 30 subjects were diagnosed with the Jara janya vyadhi, selected randomly and were given with 15 ml of Asthishrinkhalaghrita in the morning for 30 days. The data obtained were recorded, tabulated and statistically analyzed using appropriate statistical methods. Results: Study showed mild improvement in overall treatment. Though no statistically significant results were obtained, there was a good improvement for the patient in Climbing stairs, Sleep disturbance, Shwasa vridhi (Dyspnoea), Malabadhata (Constipation), Agni mandya (loss of appetite)and weight gain with p value<0.05 and Slatha sandhi (laxity of joints)and walking with p value > 0.05. Conclusion: Thus Rasayana chikitsa can improve the longevity, positive health; provide the resistance to fight against the diseases, keeping the excellence in the tissues including mental faculties.

“Undetectable, Now What?” HIV Provider Opinions on Barriers to Healthy Aging for Older People Living with HIV in North America

Background: People living with HIV (PLWH) experience age-associated health conditions earlier than their HIV-uninfected peers and have higher rates of co-occurring conditions that impact aging. Thus, HIV providers frequently confront issues related to HIV and aging. Objective: The objective of this project was to understand provider opinions about the care of older PLWH better. Design: This was accomplished using a quantitative survey. Participants: This study involved 681 physicians treating PLWH in North America. MAIN MEASURES: We collaborated with the Emerging Infections Network (EIN) to administer a ninequestion survey covering practice characteristics, attitudes, and perceived barriers in caring for older PLWH. Key Results: Two hundred and ninety-four (43.2%) responses were collected. Providers estimate that 35% (IQR: 25-50) of their HIV-infected patients were >50 years. The majority (72%) agreed it is difficult to care for older PLWH but had confidence in their ability to do so (85%). Most list a lack of time (55.4%) and insufficient multidisciplinary support (58.5%) as limitations to the effective management of older PLWH. Multi-morbidity was overwhelmingly perceived as the most important barrier to healthy aging (62.2%) followed by tobacco/alcohol use (10%), low income/savings (8.2%), polypharmacy (4.8%) and mental illness (4.4%). Loneliness, frailty, and cognitive difficulties were judged to be less important. In conclusion, HIV providers recognized the complexity of caring for older PLWH, and yet were confident they could care for this population. Conclusion: Multi-morbidity was identified as a major barrier to healthy aging, while syndromes such as frailty and cognitive difficulties were deemed less important despite a growing body of evidence that these geriatric syndromes are common in older PLWH.

Chemotherapy-induced cellular senescence suppresses progression of Notch-driven T-ALL.

T cell acute lymphoblastic leukemia (T-ALL) is a serious hematologic malignancy that occurs in children and young adults. Current therapies include intensive chemotherapy and ionizing radiation that preferentially kill malignant cells. Unfortunately, they are frequently accompanied by unintended negative impacts, including the induction of cellular senescence and long-term toxicities in normal host tissues. Whether these senescent cells resulting from therapy increase the susceptibility to relapse or secondary cancers is unknown. Using transgenic and pharmacological approaches to eliminate doxorubicin-induced senescent cells in a Notch-driven T-ALL relapse mouse model, we find that these cells inhibit tumor recurrence, suggesting that senescence in response to treatment suppresses tumorigenesis. This finding, together with extensive evidence from others demonstrating that age-associated health problems develop dramatically earlier among childhood cancer survivors compared to age-matched counterparts, suggests a relationship between therapy-induced senescence and tumorigenesis. Although cancer risk is increased through accelerated premature-aging in the long run, therapy-induced senescence appears to protect survivors from recurrence, at least in the short run.

Association of Obesity with DNA Methylation Age Acceleration in African American Mothers from the InterGEN Study.

African American women are affected by earlier onset of age-associated health deteriorations and obesity disproportionally, but little is known about the mechanism linking body mass index (BMI) and biological aging among this population. DNA methylation age acceleration (DNAm AA), measuring the difference between DNA methylation age and chronological age, is a novel biomarker of the biological aging process, and predicts aging-related disease outcomes. The present study estimated cross-tissue DNA methylation age acceleration using saliva samples from 232 African American mothers. Cross-sectional regression analyses were performed to assess the association of BMI with DNAm AA. The average chronological age and DNA methylation age were 31.67 years, and 28.79 years, respectively. After adjusting for smoking, hypertension diagnosis history, and socioeconomic factors (education, marital status, household income), a 1 kg/m2 increase in BMI is associated with 0.14 years increment of DNAm AA (95% CI: (0.08, 0.21)). The conclusion: in African American women, high BMI is independently associated with saliva-based DNA methylation age acceleration, after adjusting for smoking, hypertension, and socioeconomic status. This finding supports that high BMI accelerates biological aging, and plays a key role in age-related disease outcomes among African American women.

Novel age-associated DNA methylation changes and epigenetic age acceleration in middle-aged African Americans and whites

BackgroundAfrican Americans (AAs) experience premature chronic health outcomes and longevity disparities consistent with an accelerated aging phenotype. DNA methylation (DNAm) levels at specific CpG positions are hallmarks of aging evidenced by the presence of age-associated differentially methylated CpG positions (aDMPs) that are the basis for the epigenetic clock for measuring biological age acceleration. Since DNAm has not been widely studied among non-European populations, we examined the association between DNAm and chronological age in AAs and whites, and the association between race, poverty, sex, and epigenetic age acceleration.ResultsWe measured genome-wide DNA methylation (866,836 CpGs) using the Illumina MethylationEPIC BeadChip in blood DNA extracted from 487 middle-aged AA (N = 244) and white (N = 243), men (N = 248), and women (N = 239). The mean (sd) age was 48.4 (8.8) in AA and 49.0 (8.7) in whites (p = 0.48). We identified 4930 significantly associated aDMPs in AAs and 469 in whites. Of these, 75.6% and 53.1% were novel, largely driven by the increased number of measured CpGs in the EPIC array, in AA and whites, respectively. AAs had more age-associated DNAm changes than whites in genes implicated in age-related diseases and cellular pathways involved in growth and development. We assessed three epigenetic age acceleration measures (universal, intrinsic, and extrinsic). AAs had a significantly slower extrinsic aging compared to whites. Furthermore, compared to AA women, both AA and white men had faster aging in the universal age acceleration measure (+ 2.04 and + 1.24 years, respectively, p < 0.05).ConclusionsAAs have more wide-spread methylation changes than whites. Race and sex interact to underlie biological age acceleration suggesting altered DNA methylation patterns may be important in age-associated health disparities.

Cancer treatment decision-making with/ for older adults with dementia: the intersections of autonomy, capital, and power

ABSTRACTIn healthcare, health risk assessments are influenced by technical ‘objective’ measurements of the physical body and disease; the values that underlie professional practices (such as beneficence, non-maleficence, and autonomy); the organisations healthcare professionals work for; and subjective belief systems of individual healthcare professionals. As a result, cancer treatments prescribed for older adults can be tempered by personal views about a patient’s age, and other age-associated health conditions or comorbidities that they may have. Drawing from interviews undertaken with nine key staff members in a large cancer service, we examine how treatment recommendations and decisions are determined when older adults with cancer also have dementia; two health conditions more common in older age. Our analysis reveals two themes that underlie the complicated processes of risk-benefit assessment in treatment decision-making: the unequal distribution of capital and power between health workers; and whether older adults with cancer and dementia are assessed as solely individuals or embedded in supportive social networks (individual versus relational autonomy). This analysis exposes capital and personal beliefs about dementia are implicit in health risk assessments for older adults who have cancer and dementia which, in conjunction with organisational constraints, significantly influence how treatment recommendations and decisions are reached.

Synergistic Effect of Rapamycin and Metformin Against Age-Dependent Oxidative Stress in Rat Erythrocytes.

Erythrocytes are particularly vulnerable toward age-dependent oxidative stress-mediated damage. Caloric restriction mimetics (CRMs) may provide a novel strategy for the maintenance of redox balance as well as effective treatment of age-associated diseases. Herein, we have investigated the beneficial effect of cotreatment with CRM-candidate drugs, rapamycin (an immunosuppressant drug and inhibitor of mammalian target of rapamycin) and metformin (an antidiabetic biguanide and activator of adenosine monophosphate kinase), against aging-induced oxidative stress in erythrocytes and plasma of aging rats. Male Wistar rats of age 4 (young) and 24 months (old) were coexposed to rapamycin (0.5 mg/kg body weight [b.w.]) and metformin (300 mg/kg b.w.), and data were compared with the response of rats receiving an independent exposure to these chemicals at similar doses. The exposure of individual candidate drugs significantly reversed the age-dependent alterations in the endpoints associated with oxidative stress such as reactive oxygen species, ferric reducing ability of plasma, malondialdehyde, reduced glutathione, plasma membrane redox system, plasma protein carbonyl, and acetyl cholinesterase in erythrocytes and plasma of aging rats. However, the cotreatment with rapamycin and metformin showed a significant augmented effect compared with individual drug interventions on reversal of these age-dependent biomarkers of oxidative stress, suggesting a synergistic response. Thus, the findings open up further possibilities for the design of new combinatorial therapies to prevent oxidative stress- and age-associated health problems.

Two-Year High-Intensity Aerobic Training Program Prevents Age-Associated Health Risk Factor Development in Sedentary Middle-Aged Adults

Two-Year High-Intensity Aerobic Training Program Prevents Age-Associated Health Risk Factor Development in Sedentary Middle-Aged Adults