Age-related Impairment Research Articles

Egg size variation in the context of polyandry: a case study using long-term field data from snowy plovers.

Gamete size variation between the sexes is central to the concept of sex roles, however, to what extent gamete size variation within the sexes relates to sex role variation remains unclear. Comparative and theoretical studies suggest that, when clutch size is invariable, polyandry is linked to a reduction of egg size, while increased female-female competition for mates favors early breeding when females cannot monopolize multiple males. To understand whether and how breeding phenology, egg size, and mating behavior are related at the individual level, we studied the reproductive histories of 424 snowy plover females observed in the wild over a 15-year period. Egg size, but not polyandry, were highly repeatable for individual females. Consistent with theoretical predictions, we found that polyandrous females were the earliest breeders and that early clutches contained smaller eggs than clutches initiated later. Neither egg size nor mating behavior showed clear signs of an age-related deterioration, on the contrary, prior experience acquired either through age or local recruitment enabled females to nest early. Taken together, these results suggest that gamete size variation is not linked to mating behavior at the individual level, and, consequently, the adaptive potential of such variation appears to be limited.

Maternal Hyperglycemia Induces Autonomic Dysfunction and Heart Failure in Older Adult Offspring.

Offspring exposed to an adverse fetal environment, such as gestational diabetes, may manifest increased susceptibility to several chronic diseases later in life. In the present study, the cardiovascular function of three different ages of offspring from diabetic rats was evaluated. Diabetes mellitus was induced in pregnant rats by a single dose of streptozotocin (50 mg/kg). The offspring from diabetic (OD) and control rats (OC) were evaluated at three different ages: 6, 12 or 18 months. In the corresponding OC groups, fasting glycemia, baseline mean arterial pressure, and sympathetic tonus increased in the OD rats at 12 (OD12) and 18 (OD18) months of age, while cardiac hypertrophy was observed in all OD groups. Cardiac function evaluation in vivo showed low left ventricular systolic pressure and+dP/dt in the OD18 rats, suggesting a systolic dysfunction. OD12 and OD18 groups showed high left ventricle end-diastolic pressure, suggesting a diastolic dysfunction. OD groups showed an age-related impairment of both baroreflex-mediated tachycardia and baroreflex-mediated bradycardia in OD12 and OD18 rats. In isolated hearts from OD18 rats, both inotropic and tachycardiac responses to increasing isoproterenol were significantly reduced compared to the corresponding OC group. These results suggest that gestational diabetes triggers the onset of hyperglycemia hypertension with impaired baroreflex sensitivity and heart failure in older age of offspring, representing important risk factors for death. Therefore, ensuring optimal glycemic control in diabetic pregnancy is important and serves as a key to preventing cardiovascular disease in the offspring in their older age.

Functional, Morphological and Molecular Changes Reveal the Mechanisms Associated with Age-Related Vestibular Loss.

Age-related loss of vestibular function and hearing are common disorders that arise from the loss of function of the inner ear and significantly decrease quality of life. The underlying pathophysiological mechanisms are poorly understood and difficult to investigate in humans. Therefore, our study examined young (1.5-month-old) and old (24-month-old) C57BL/6 mice, utilizing physiological, histological, and transcriptomic methods. Vestibular sensory-evoked potentials revealed that older mice had reduced wave I amplitudes and delayed wave I latencies, indicating reduced vestibular function. Immunofluorescence and image analysis revealed that older mice exhibited a significant decline in type I sensory hair cell density, particularly in hair cells connected to dimorphic vestibular afferents. An analysis of gene expression in the isolated vestibule revealed the upregulation of immune-related genes and the downregulation of genes associated with ossification and nervous system development. A comparison with the isolated cochlear sensorineural structures showed similar changes in genes related to immune response, chondrocyte differentiation, and myelin formation. These findings suggest that age-related vestibular hypofunction is linked to diminished peripheral vestibular responses, likely due to the loss of a specific subpopulation of hair cells and calyceal afferents. The upregulation of immune- and inflammation-related genes implies that inflammation contributes to these functional and structural changes. Furthermore, the comparison of gene expression between the vestibule and cochlea indicates both shared and distinct mechanisms contributing to age-related vestibular and hearing impairments. Further research is necessary to understand the mechanistic connection between inflammation and age-related balance and hearing disorders and to translate these findings into clinical treatment strategies.

Plasma pentosidine as a useful biomarker of sarcopenia, low gait speed, and mortality in patients with cirrhosis.

The accumulation of advanced glycation end products (AGEs) is associated with various diseases and age-related impairments, including loss of muscle mass and function. We investigated the association between plasma pentosidine, which is one of the AGEs, and sarcopenia, low gait speed, and mortality in patients with cirrhosis. This retrospective study divided 128 patients with cirrhosis into three groups by 25th and 75th quartiles of baseline plasma pentosidine levels: low (L)-, intermediate (I)-, and high (H)-pentosidine (Pen) groups. Sarcopenia was diagnosed following the Japan Society of Hepatology criteria. Low gait speed was defined as <0.8 m/s. The cumulative survival rates were compared between the three groups. Cox proportional hazards regression analysis was performed to identify independent factors associated with mortality. Of the 128 patients, 40 (31.3%) and 34 (26.6%) had sarcopenia and low gait speed, respectively. The prevalence of sarcopenia and low gait speed significantly increased stepwise with increasing plasma pentosidine levels, with the highest in the H-Pen group (59.4% [19/32] and 56.3% [18/32], respectively) and lowest in the L-Pen group (18.8% [6/32] and 6.3% [2/32], respectively). Multivariate analysis identified plasma pentosidine levels as a significant and independent factor associated with sarcopenia (odds ratio [OR], 1.07; p = 0.036) and low gait speed (OR, 1.06; p = 0.036), with the cutoff levels of 0.0792 μg/mL (sensitivity/specificity, 0.600/0.773) and 0.0745 μg/mL (sensitivity/specificity, 0.735/0.691), respectively. The cumulative survival rates were significantly lower in the H-Pen group than in the L-Pen (hazard ratio [HR], 11.7; p = 0.001) and I-Pen (HR, 4.03; p < 0.001) groups. Plasma pentosidine levels were identified as a significant and independent prognostic factor (HR, 1.07; p < 0.001). Plasma pentosidine levels are associated with sarcopenia, low gait speed, and mortality and may serve as a useful surrogate biomarker for these clinical events in patients with cirrhosis.

INCIDENCE OF ACUTE KIDNEY INJURY IN PATIENTS OF ACUTE GASTROENTERITIS ADMITTED AT LADY READING HOSPITAL, PESHAWAR

Acute gastroenteritis affects all age groups alike, is a common cause of hospitalization worldwide, and is the most common known cause of preventable acute kidney injury. AKI may be defined as a sudden decrease in kidney function, which results in reduced filtration capability of the kidneys, accumulation of waste products, and their resultant clinical manifestations. The level of insult may range from mild to severe, requiring simple oral rehydration most times, while in a few cases needing intervention in the form of hemodialysis. The elderly population is more prone to develop AKI due to age-related deterioration in renal function. An overall positive outcome has been associated with early hemodialysis in progressively deteriorating AKI and critically ill patients. A prospective observational study was conducted on 40 patients with AKI secondary to acute gastroenteritis admitted to MTI, Lady Reading Hospital, Peshawar, KP, Pakistan, from February 2023 to June 2023. These patients were selected from 142 patients with acute gastroenteritis admitted to MTI, Lady Reading Hospital, Peshawar. Data collected was analyzed using SPSS 20. This study was conducted on 40 patients with a mean age of 39.82±16.54 years. Gender: Our study included 22 (55%) male and 18 (45%) female patients. We observed that 11 (27.5%) patients on dialysis had developed AKI secondary to AGE. We observed that older patients above 40 years of age who developed AKI secondary to AGE had a significantly higher frequency of hemodialysis (47.1%) as compared to patients less than 40 years of age (13%) (P = 0.01). According to the comparison of mortality with age groups, no mortality was seen in the age group of &lt; = 40 years; however, there were 2 mortalities in the age group of &gt; 40 years. One patient expired after 2 sessions, and one expired after 5 sessions and a prolonged stay. Our results showed a significant association between favorable outcomes and dialysis sessions for the less than 40 age group (P = 0.0001) and the more than 40 age group (P = 0.004). Although the overall outcome with dialysis was favorable, with good recovery, the age group of 40 years and above showed significantly higher rates of hemodialysis requirement and more morbidity and mortality compared to the age group of 40 years and less. 40(28.2%) patients with Acute gastroenteritis developed Acute kidney injury. Among these patients, 11 (27.5%) required hemodialysis. This concluded that 29 patients (72.5%) were treated conservatively and discharged with full recovery of renal function. 72.7% requiring hemodialysis were above 40 years of age, proving that the incidence of AKI and its severity increased.

Geroprotective interventions converge on gene expression programs of reduced inflammation and restored fatty acid metabolism

Understanding the mechanisms of geroprotective interventions is central to aging research. We compare four prominent interventions: senolysis, caloric restriction, in vivo partial reprogramming, and heterochronic parabiosis. Using published mice transcriptomic data, we juxtapose these interventions against normal aging. We find a gene expression program common to all four interventions, in which inflammation is reduced and several metabolic processes, especially fatty acid metabolism, are increased. Normal aging exhibits the inverse of this signature across multiple organs and tissues. A similar inverse signature arises in three chronic inflammation disease models in a non-aging context, suggesting that the shift in metabolism occurs downstream of inflammation. Chronic inflammation is also shown to accelerate transcriptomic age. We conclude that a core mechanism of geroprotective interventions acts through the reduction of inflammation with downstream effects that restore fatty acid metabolism. This supports the notion of directly targeting genes associated with these pathways to mitigate age-related deterioration.

Long-term experience on assisted suicide in Switzerland: dementia, mental disorders, age-related polymorbidity and the slippery slope argument

ObjectivesAccording to the Swiss medico-ethical guidelines valid between 2004 and 2018, the key criterion for assisted suicide (AS) was that the patients who wished to die suffered with a disease leading to death in the foreseeable future. Critics of AS fears that broadening of the medical indications will lead to an uncontrolled expansion to persons who are not terminally ill (slippery slope argument). We evaluated to what extent this broadening took place in practice over time. Study designRetrospective national cohort study. MethodsBy using data of the Swiss Federal Statistical Office, we analyzed the long-term development of AS in Switzerland over a 20-year period (1999–2018; n = 8738 cases). We classified the cases into one of three categories regarding the aforementioned key criterion for AS. ResultsIn 43.6% of AS cases, the criterion ‘end of life is near’ was met. In 5.3% of cases, this criterion was not met (4.7%: mental disorders; 0.6%: dementia). In 51.1% of cases, the reason underlying AS comprised several, mostly age-related diseases and/or functional impairments; the aforementioned key criterion, however, was probably not met in most of the cases. Over time, the number of cases doubled over each 5-year period; this increase occurred similarly for the three categories. ConclusionThe fact that many AS cases took place outside the valid medico-ethical guidelines might be interpreted as a development in the idea of the slippery slope argument. The fact that the percentage distribution of these cases remained unchanged over time argues against it.

The Benefits of Water from Nitrodi's Spring: The In Vitro Studies Leading the Potential Clinical Applications.

Natural products (water, plants, and minerals) have been studied for diverse applications in health and disease. Since there has been a growing interest in the introduction of thermal water as a clinical complementary approach in the treatment of low-grade inflammation and stress-related conditions, this review focuses on the oldest spa in the world: Nitrodi's spring. Substantial studies in the 1960s showed that both the internal and external use of Nitrodi's water yielded several benefits in physiological processes and in treating certain disorders, mainly allergic and autoimmune inflammatory conditions. More recently, a novel interest in Nitrodi's water has prompted researchers to further explore the effects of this water and shed light on the molecular mechanisms sustaining its therapeutic efficacy. In different epithelial cell models, Nitrodi's water had strong promotional effects on proliferation, cell migration, cell viability, and fibroblast to myofibroblast transition, all of which essential for wound healing and tissue remodeling. Moreover, Nitrodi's water exhibited anti-oxidant and anti-inflammatory properties through the inhibition of ROS production and protein S-nitrosylation. Here, we have collected the clinical and basic data on Nitrodi's water and reviewed articles that have discussed its use as a potential treatment for several inflammatory and autoimmune diseases and age-related skin deterioration.

Abstract 108: Rejuvenation Potential Of Extracellular Vesicles From Renal Distal Tubular Cells - A Promising Strategy To Prevent Aging-associated Hypertension And Renal Function Impairment

Ageing is characterized by progressive multi-organ functional decline and disrupted homeostasis adaptation. Hypertension and kidney damage become increasingly prevalent as individuals age. Given its high metabolic activity and constant exposure to reactive oxygen species, the kidney is particularly susceptible to age-related deterioration. In our study, aged mice exhibited a notable decline in glomerular filtration rate (GFR) and urinary excretion of sodium, potassium, and calcium, alongside elevated urinary creatinine levels, indicating impaired renal function associated with ageing. Histologically, aged kidneys showed glomerular collapse, thickening of the glomerular basement membrane, and increased glomerular sclerosis. Cellular senescence plays a critical role in renal ageing. Senescent cells display an array of changes in gene and protein expression and thus also altered the contents packaged into extracellular vesicles (EVs), secreted into the extracellular milieu. The protein and RNA composition of EVs varied depending on the age and pathological status of the originating parent cells. Our data showed an increased expression of EV biogenesis protein HRS (hepatocyte growth factor-regulated tyrosine kinase substrate) in aged DCT cells (aDCTs). Consistently, with an increase in EV secretion in aDCTs. Administration of young DCT (yDCT)-derived EVs into aged kidneys resulted in a significant improvement of GFR and urinary ion excretion, accompanied by a reduction in age-associated elevation of systolic blood pressure (SBP). Conversely, when administering aDCT-derived EVs to young mice, we saw a significant decrease in GFR and an increase in SBP, indicating a detrimental effect of aDCT-EVs. Proteomic analysis revealed distinct protein expression profiles between yDCT-EVs and aDCT-EVs. These differentially expressed proteins are highly enriched in ageing regulatory pathways, underscoring the crucial role of DCT-EVs in kidney rejuvenation. Intriguingly, we identified a subset of proteins exclusively present in either yDCT-EVs or aDCT-EVs. Our future research will focus on identifying the key components of DCT-EVs responsible for driving kidney rejuvenation.

Neuronal activation of Gαq EGL-30/GNAQ late in life rejuvenates cognition across species

Loss of cognitive function with age is devastating. EGL-30/GNAQ and Gαq signaling pathways are highly conserved between C.elegans and mammals, and murine Gnaq is enriched in hippocampal neurons and declines with age. We found that activation of EGL-30 in aged worms triples memory span, and GNAQ gain of function significantly improved memory in aged mice: GNAQ(gf) in hippocampal neurons of 24-month-old mice (equivalent to 70- to 80-year-old humans) rescued age-related impairments in well-being and memory. Single-nucleus RNA sequencing revealed increased expression of genes regulating synaptic function, axon guidance, and memory in GNAQ-treated mice, and worm orthologs of these genes were required for long-term memory extension in worms. These experiments demonstrate that C.elegans is a powerful model to identify mammalian regulators of memory, leading to the identification of a pathway that improves memory in extremely old mice. To our knowledge, this is the oldest age at which an intervention has improved age-related cognitive decline.

Effects of Regular Aerobic Exercise Interventions on Decreased Cerebral Blood Flow-Induced Mild Cognitive Impairment

PURPOSE: Decreased cerebral blood flow (CBF) is a common symptom in older adults with mild cognitive impairment (MCI). Aerobic exercise is a promising therapeutic intervention for delaying or ameliorating age-related CBF deterioration in older individuals. The review outlines the differences in CBF between healthy older individuals and those with MCI, as well as the benefits of aerobic exercise in augmenting CBF in older adults.METHODS: We used academic search engines, including PubMed, Web of Science, Scopus, Google Scholar, and the Wiley Online Library, to identify studies demonstrating alterations in CBF with aging and the preventive and therapeutic effects of aerobic exercise on CBF in older adults. The keywords included ‘mild cognitive impairment,’ ‘elderly or older people,’ ‘cerebral blood flow,’ ‘cerebral perfusion,’ and ‘aerobic exercise.’RESULTS: Aerobic exercise improves or maintains health by enhancing CBF and cognitive function in healthy older individuals. The beneficial impact applies to older people with MCI, although research has been inconsistent regarding aerobic exercise-induced alterations in CBF.CONCLUSIONS: Aerobic exercise is a promising treatment for MCI in older adults and promotes CBF and cognitive function. However, some studies have reported inconsistent findings regarding changes in CBF. The inconsistencies may be due to several factors, including health and age. Further investigations are warranted to delineate the effects of aerobic exercise on CBF in older adults with MCI.

Phytochemical and Therapeutic Potential of Herbal Cognitive Enhancer

Memory is the most significant factor in distinguishing one person from another, as it is necessary to recognise one’s own self. The brain can encode, store, and retrieve information using three different types of memory. Individuals who lack these basic forms of memory are unable to create personal relationships, acquire new knowledge, and perform basic everyday duties. Memory refers to a person’s ability to encode, store, retain, and recall knowledge and past events in his or her brain. Memory gives a person the ability to learn from and adapt to previous experiences, as well as the ability to recall previously taught facts, skills, and habits. Today, poor memory, weak recall, and low retention are all typical issues. Memory deteriorates primarily because of stress and exhaustion. Memory loss, often known as age-related memory impairment, is frequent in those over the age of 40. This could be linked to the loss of hormones and proteins (growth factors) that repair brain cells as people get older. Herbs were employed to improve memory power in India throughout ancient times. Indian and Chinese cultures developed many traditional medicines from herbs to treat diminishing cognition, reverse memory loss, and improve learning power. Nootropic herbs are known for their brain-acting herbs and smart medications, which are derived from their isolated ingredients and aid to improve blood circulation in the brain. The focus of this review is on natural agents and herbs that work as memory enhancers. By using one of the herbs at a time, one can improve his or her memory.

Predicting Elderly Falls Using the Roll Factor in the "Smart Walk Trainer" Equipment for Body Weight-Balance Analysis

The imbalanced posture of the body is a potential risk of accidents in all ages that can be caused by a variety of reasons, including muscle weakness, aging-related deterioration in balance, or neurological problems, possibly see more problem for the elderly. Knowing the weight-bearing condition would be helpful to improve balance of the body to prevent the risk. The “Smart Walk Trainer” equipment has been developed for analyzing the imbalance weight-bearing conditions of both standing and walking manner. It consists of "Force Sensitive Resistor" (FSR) sensors to measure the weight-bearing of the foot, the controlling and processing system of the NI USB-6009 multifunction I/O hardware, and LabVIEW software. The study using this equipment aims to examine the differences between young and elderly subjects in terms of weight-bearing and balance assessment. The result showed the roll_factor of the elderly deviated greatly from the balance point (Right: Mean = -0.72, SD = 1.4; Left: Mean=0.78, SD=1.41) when compared to the young subjects (Right: Mean = 0.01, SD = 0.56; Left: Mean=-0.19, SD = 0.49) which corresponded to the risk of falling in the elderly. The equipment also provides specialists with enhanced clarity regarding weight distribution patterns, enabling them to identify any abnormalities and then provide targeted exercise recommendations to strengthen specific muscles and promote improved balance for fall prevention.

Trends in health service needs, utilization, and non-communicable chronic diseases burden of older adults in China: evidence from the 1993 to 2018 National Health Service Survey

BackgroundAging is associated with an increased prevalence of non-communicable chronic diseases (NCDs), functional impairments, and diverse demands for health services. This study analyzed the trends in older adults’ needs and utilization of health services from 1993 to 2018 in China, as well as chronic disease-related economic burdens.MethodsThe research data were collected from the six cross-sectional National Health Service Survey (NHSS), implemented every 5 years from 1993 to 2018. A multi-stage stratified random cluster sampling method has been adopted in the NHSS. The data on the older population's socio-economic characteristics, health service needs, and utilization were collected from the 6 waves National Health Service Survey (NHSS) 1993–2018. In the 2013 and 2018 NHSSs, EQ-5D-3L and visual analogue scale were used to evaluate the health condition. And the prevalence of NCDs and related Out-of-pocket (OOP) expenditures were collected. Functional dependency and impairment were collected in 2018. The Katz Activities of Daily Living scale was used to evaluate six functions, including self-feeding, dressing, bathing, transferring, toilet hygiene, and controlling bowel movements.ResultsThe two-week morbidity rate and prevalence of NCDs showed a rapid upward trend in older adults. With the development of health system reform and universal health insurance coverage, older adults' two-week medical consultation rate increased from 25.6% in 1993 to 40.1% in 2018, and the hospitalization rate rose from 6.1% to 24.9%. The difference in health service needs and utilization between urban and rural areas decreased, and the hospitalization rate in rural areas (26.3%) exceeded that in urban areas (23.6%) for the first time in 2018. Functional independence become more severe as aged. The proportion of severe functional impairment was 6.9% and 2% in the group aged 80 or over and group 70–79 years, respectively. Regarding disability status, 32.5% had hearing problems and 31.4% had visual impairment. The highest prevalence rates of NCDs in older adults were found in hypertension (36.9%), followed by diabetes (10.6%), cerebrovascular disease (5.4%), ischemic heart disease (4.5%), and intervertebral disc disease (4.2%). The average annual OOP expenditures attributed to NCDs increased from ¥2481.8 RMB in 2013 to ¥8255.9 RMB in 2018 for older adults. About 90.7% of older adults prefer to live in the residential community, leading to the demands for preventive healthcare (30.4%), medical treatment (14.1%), and elderly education (8.6%).ConclusionThe elevated risks of age-related impairments and chronic morbidities, and increased demands for preventive healthcare are critical public health issues. Policymakers should strengthen primary healthcare and move towards integrated delivery to improve access and quality of care for older adults. The integration of healthcare and social security constitutes an adaptive trend in meeting the multi-level demands of an aging society.

Metformin, Cognitive Function, and Changes in the Gut Microbiome.

The decline in cognitive function and the prevalence of neurodegenerative disorders are among the most serious threats to health in old age. The prevalence of dementia has reached 50 million people worldwide and has become a major public health problem. The causes of age-related cognitive impairment are multiple, complex, and difficult to determine. However, type 2 diabetes (T2D) is linked to an enhanced risk of cognitive impairment and dementia. Human studies have shown that patients with T2D exhibit dysbiosis of the gut microbiota. This dysbiosis may contribute to the development of insulin resistance and increased plasma lipopolysaccharide concentrations. Metformin medication mimics some of the benefits of calorie restriction and physical activity, such as greater insulin sensitivity and decreased cholesterol levels, and hence may also have a positive impact on aging in humans. According to recent human investigations, metformin might partially restore gut dysbiosis related to T2D. Likewise, some studies showed that metformin reduced the risk of dementia and improved cognition, although not all studies are concordant. Therefore, this review focused on those human studies describing the effects of metformin on the gut microbiome (specifically the changes in taxonomy, function, and circulating metabolomics), the changes in cognitive function, and their possible bidirectional implications.

Combined effects of age and hearing impairment on utterances and requests for clarification in spontaneous conversation and a referential communication task.

The impact of hearing impairment is typically studied in terms of its effects on speech perception, yet this fails to account for the interactive nature of communication. Recently, there has been a move towards studying the effects of age-related hearing impairment on interaction, often using referential communication tasks; however, little is known about how interaction in these tasks compares toeveryday communication. To investigate utterances and requests for clarification used in one-to-one conversations between older adults with hearing impairment and younger adults without hearing impairment, and between two younger adults without hearing impairment. A total of 42 participants were recruited to the study and split into 21 pairs, 10 with two younger adults without hearing impairment and 11 with one younger adult without hearing impairment and one older participant with age-related hearing impairment (hard of hearing). Results from three tasks-spontaneous conversation and two trials of a referential communication task-were compared. A total of 5 min of interaction in each of the three tasks was transcribed, and the frequency of requests for clarification, mean length of utterance and total utterances were calculated for individual participants and pairs. When engaging in spontaneous conversation, participants made fewer requests for clarification than in the referential communication, regardless of hearing status/age (p ≤ 0.012). Participants who were hard of hearing made significantly more requests for clarification than their partners without hearing impairment in only the second trial of the referential communication task (U = 25, p = 0.019). Mean length of utterance was longer in spontaneous conversation than in the referential communication task in the pairs without hearing impairment (p ≤ 0.021), but not in the pairs including a person who was hard of hearing. However, participants who were hard of hearing used significantly longer utterances than their partners without hearing impairment in the spontaneous conversation (U = 8, p < 0.001) but not in the referential communication tasks. The findings suggest that patterns of interaction observed in referential communication tasks differ to those observed in spontaneous conversation. The results also suggest that fatigue may be an important consideration when planning studies of interaction that use multiple conditions of a communication task, particularly when participants are older or hard of hearing. What is already known on this subject Age-related hearing impairment is known to affect communication; however, the majority of studies have focused on its impact on speech perception in controlled conditions. This indicates little about the impact on everyday, interactive, communication. What this study adds to the existing knowledge We investigated utterance length and requests for clarification in one-to-one conversations between pairs consisting of one older adult who is hard of hearing and one younger adult without hearing impairment, or two younger adults without hearing impairment. Results from three tasks (two trials of a referential communication task and spontaneous conversation) were compared. The findings demonstrated a significant effect of task type on requests for clarification in both groups. Furthermore, in spontaneous conversation, older adults who were hard of hearing used significantly longer utterances than their partners without hearing impairment. This pattern was not observed in the referential communication task. What are the potential or actual clinical implications of this work? These findings have important implications for generalizing results from controlled communication tasks to more everyday conversation. Specifically, they suggest that the previously observed strategy of monopolizing conversation, possibly as an attempt to control it, may be more frequently used by older adults who are hard of hearing in natural conversation than in a more contrived communication task.

Platelet-derived exerkine CXCL4/platelet factor 4 rejuvenates hippocampal neurogenesis and restores cognitive function in aged mice

The beneficial effects of physical activity on brain ageing are well recognised, with exerkines, factors that are secreted into the circulation in response to exercise, emerging as likely mediators of this response. However, the source and identity of these exerkines remain unclear. Here we provide evidence that an anti-geronic exerkine is secreted by platelets. We show that platelets are activated by exercise and are required for the exercise-induced increase in hippocampal precursor cell proliferation in aged mice. We also demonstrate that increasing the systemic levels of the platelet-derived exerkine CXCL4/platelet factor 4 (PF4) ameliorates age-related regenerative and cognitive impairments in a hippocampal neurogenesis-dependent manner. Together these findings highlight the role of platelets in mediating the rejuvenating effects of exercise during physiological brain ageing.

Perspectives of older people with uncontrolled type 2 diabetes mellitus towards medication adherence: A qualitative study.

Better medication adherence among people with diabetes mellitus was found to be associated with improved glycaemic control. However, medication non-adherence is a significant concern in older people with uncontrolled type 2 diabetes mellitus. To explore the perspectives of older people with uncontrolled type 2 diabetes mellitus towards medication adherence. A qualitative descriptive exploratory study. A purposive sample of older people with uncontrolled type 2 diabetes mellitus living in the community was recruited. Snowball sampling was applied in community recruitment. In-depth telephone interviews were conducted using a semi-structured interview guide. Interviews were transcribed verbatim. Thematic analysis was used in data analysis. The consolidated criteria for reporting qualitative research (COREQ) guidelines were followed. The emerged six themes were: (a) impact of knowledge, attitudes and practices on medication adherence, (b) treatment-related barriers to medication adherence, (c) impact of age-related changes on medication adherence, (d) person-related barriers to medication adherence, (e) impact of COVID-19 on medication adherence and, (f) role of support systems in medication adherence. Knowledge of the disease process and medications, attitudes towards medication adherence, the practice of different treatment approaches, self-medication and dosing, negative experiences related to medications, polypharmacy, changes in lifestyle and roles, the influence of work-life, motivation, negligence, family support, support received from health workers, facilities available and financial capability are the main factors influence medication adherence. Age-related memory impairment, visual disturbances and physical weaknesses affect medication adherence in older people. Additionally, COVID-19-related guidelines imposed by the government and healthcare system-related issues during the COVID-19 pandemic also affected medication adherence. Adherence to medications among older people is hampered by a variety of factors, including their knowledge, attitudes and practices, person and treatment-related factors and age-related changes. The COVID-19 pandemic has brought additional challenges. Individualised patient care for older people with uncontrolled type 2 diabetes mellitus to improve medication adherence is timely. Strengthening support mechanisms for the above population is essential.

The Effect of the Human Brainstem Myelination on Gait Speed in Normative Aging.

The brainstem functions as a relay and integrative brain center and plays an essential role in motor function. Whether brainstem tissue deterioration, including demyelination, affects motor function has not been studied. Understanding the potential relationship between brainstem demyelination and motor function may be useful for the early diagnosis of neurodegenerative diseases and to understand age-related gait impairments that have no apparent cause. In this work, we investigated the associations between rapid or usual gait speeds, as integrative measures of motor function, and cerebral myelin content. In 118 individuals (age 22-94 years) free of neurodegenerative diseases or cognitive impairment, myelin content was assessed as the myelin water fraction, a direct magnetic resonance imaging measure of myelin content, and longitudinal and transverse relaxation rates (R1 and R2), which are sensitive magnetic resonance imaging measures of myelin content. Our results indicate that participants with lower usual or rapid gait speed exhibited lower values of myelin water fraction and R1 in the main brainstem regions, which were more evident and statistically significant in the midbrain. In contrast, we found no significant associations between gait speeds and R2, an expected result because various physiological factors confound R2. These original findings provide evidence that the level of brainstem myelination may affect gait performance among cognitively unimpaired adults who are free from any clinically detectable neurodegenerative diseases. Further studies are needed to understand the longitudinal changes in brainstem myelination with aging and neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease.

Effects of Adult Age and Functioning of the Locus Coeruleus Norepinephrinergic System on Reward-Based Learning.

Age-related impairments in value representations and updating during decision-making and reward-based learning are often related to age-related attenuation in the catecholamine system such as dopamine (DA) and norepinephrine (NE). However, it is unclear to what extent age-related declines in NE functioning in humans affect reward-based decision-making. We conducted a probabilistic decision-making task and applied a Q-learning model to investigate participants' anticipatory values and value sensitivities. Task-related pupil dilations and locus coeruleus (LC) magnetic resonance imaging (MRI) contrast, which served as a potential window of the LC-NE functions, were assessed in younger and older adults. Results showed that in both choice and feedback phases, younger adults' (N = 42, 22 males) pupil dilations negatively correlated with anticipatory values, indicating uncertainty about outcome probabilities. Uncertainty-evoked pupil dilations in older adults (N = 41, 27 males) were smaller, indicating age-related impairments in value estimation and updating. In both age groups, participants who showed a larger uncertainty-evoked pupil dilation exhibited a higher value sensitivity as reflected in the β parameter of the reinforcement Q-learning model. Furthermore, older adults (N = 34, 29 males) showed a lower LC-MRI contrast than younger adults (N = 25, 15 males). The LC-MRI contrast positively correlated with value sensitivity only in older but not in younger adults. These findings suggest that task-related pupillary responses can reflect age-related deficits in value estimation and updating during reward-based decision-making. Our evidence with the LC-MRI contrast further showed the age-related decline of the LC structure in modulating value representations during reward-based learning.SIGNIFICANCE STATEMENT Age-related impairments in value representation and updating during reward-based learning are associated with declines in the catecholamine modulation with age. However, it is unclear how age-related declines in the LC-NE system may affect reward-based learning. Here, we show that compared with younger adults, older adults exhibited reduced uncertainty-induced pupil dilations, suggesting age-related deficits in value estimation and updating. Older adults showed a lower structural MRI of the LC contrast than younger adults, indicating age-related degeneration of the LC structure. The association between the LC-MRI contrast and value sensitivity was only observed in older adults. Our findings may demonstrate a pioneering model to unravel the role of the LC-NE system in reward-based learning in aging.