Evidence Of Age-related Changes Research Articles

LAMP2A, and other chaperone-mediated autophagy related proteins, do not decline with age in genetically heterogeneous UM-HET3 mice.

Chaperone-mediated autophagy (CMA) selectively degrades proteins that are crucial for glycolysis, fatty acid metabolism, and the progression of several age-associated diseases. Several previous studies, each of which evaluated males of a single inbred mouse or rat strain, have reported that CMA declines with age in many tissues, attributed to an age-related loss of LAMP2A, the primary and indispensable component of the CMA translocation complex. This has led to a paradigm in the field of CMA research, stating that the age-associated decline in LAMP2A in turn decreases CMA, contributing to the pathogenesis of late-life disease. We assessed LAMP2A levels and CMA substrate uptake in both sexes of the genetically heterogeneous UM-HET3 mouse stock, which is the current global standard for the evaluation of anti-aging interventions. We found no evidence for age-related changes in LAMP2A levels, CMA substrate uptake, or whole liver levels of CMA degradation targets, despite identifying sex differences in CMA.

Age-related changes in lumbar bone mineral density measured using quantitative computed tomography in healthy female cynomolgus monkeys.

Cynomolgus monkeys are widely used in studies related to osteoporosis, and there is no evidence of age-related changes in volumetric bone mineral density (vBMD) measured using quantitative computed tomography (QCT) in nonhuman primates. This study aimed to describe changes in the characteristics of lumbar vBMD with age, to analyze the relationship between lumbar vBMD and body composition, and to investigate the precision of QCT measurements in healthy female cynomolgus monkeys. Age-related changes in lumbar vBMD were described using cubic regression models, and the accumulated bone loss rates (ABLR) of the lumbar spine were calculated. Spearman rank correlation and ridge regression analysis were used to investigate the relationship of the average lumbar vBMD and body components. Thirty animals were selected to analyze the short-term in vivo precision of the QCT measurements. The precision was expressed as the root-mean-square coefficient of variation (RMS-CV%) or root-mean-square standard deviation (RMS-SD). A total of 72 healthy female cynomolgus monkeys, aged 1-25 years, were included in this study. The average lumbar vBMD of female cynomolgus monkeys increased with age until the age of 10 years, around which it reached peak bone mass, with a relatively marked decline after the age of 13 years. The ABLRs of female cynomolgus monkeys in the premenopausal (13-19 years) and postmenopausal age groups (20-25 years) were -4.9% and -21.2%, respectively. Ridge regression analysis showed that age and subcutaneous adipose tissue (SAT) contributed positively to the average lumbar vBMD in animals aged ≤10 years, whereas in animals aged >10 years, age contributed negatively to lumbar vBMD. The RMS-CV% (RMS-SD) of the lumbar vBMD measured using QCT ranged from 0.47% to 1.60% (1.91-6.31 mg/cm3). Age-related changes in lumbar vBMD measured using QCT in healthy female monkeys showed similar trends to those in humans. Age and SAT may affect the lumbar vBMD in female cynomolgus monkeys. QCT revealed good precision in measuring the lumbar vBMD in female cynomolgus monkeys.

Screening for balance in children and adults in a community science education setting: Normative data, influence of age, sex, and body mass index, and feasibility.

BackgroundScreening standing and walking balance is useful for people suspected of having vestibular disorders, a variety of neurologic and musculoskeletal disorders, and for screening astronauts returning after exposure to microgravity. Visitors to a community science education center children and adults, aged 4 to 85, were tested on tandem walking with eyes closed and the modified Romberg test on compliant foam. They were then asked about their experience participating in research, many people for the first time.MethodsSubjects performed 10 steps of tandem walking with eyes closed, and three trials of the modified Romberg, or Clinical Test of Sensory Integration and Balance, with eyes closed, standing on compliant memory foam, with a) head still, b) head shaking in yaw, and c) head nodding in pitch. Afterward, staff queried subjects about the experience of participating in science.ResultsAge-related changes across the life span occurred in both sets of tests. Therefore, look-up tables by age are provided. Body mass index significantly affected tandem walking. Some sex differences were found. The tests were easy to administer in a community setting. Most participants enjoyed the experience and reported that they learned about the process of scientific research.DiscussionThese data support and extend the evidence for age-related changes in balance performance across the lifespan and for an influence of body mass index on some balance skills. Clinicians and sports educators should be cognizant of these differences when they use these tests for screening. The community science education environment provided a useful laboratory in which to collect valid and reliable data, while simultaneously educating participants about the process of science.

P85. Sex Differences in Regional Patterns of Brain-Age-Gap Estimates

Neuroimaging studies have been instrumental in identifying sex-differences in brain structure, and there is robust evidence for age-related changes in brain structure throughout the lifespan. However, the literature on sex-differences in regional patterns of age-related changes in young adulthood remains limited. To address this, we availed of a machine learning model to obtain local brain-age-gap estimates (L-brainAGE), which reflect voxel-wise differences between an individual’s chronological and biological brain age.

Age-related change in task-evoked amygdala-prefrontal circuitry: A multiverse approach with an accelerated longitudinal cohort aged 4-22 years.

The amygdala and its connections with medial prefrontal cortex (mPFC) play central roles in the development of emotional processes. While several studies have suggested that this circuitry exhibits functional changes across the first two decades of life, findings have been mixed ‐ perhaps resulting from differences in analytic choices across studies. Here we used multiverse analyses to examine the robustness of task‐based amygdala—mPFC function findings to analytic choices within the context of an accelerated longitudinal design (4–22 years‐old; N = 98; 183 scans; 1–3 scans/participant). Participants recruited from the greater Los Angeles area completed an event‐related emotional face (fear, neutral) task. Parallel analyses varying in preprocessing and modeling choices found that age‐related change estimates for amygdala reactivity were more robust than task‐evoked amygdala—mPFC functional connectivity to varied analytical choices. Specification curves indicated evidence for age‐related decreases in amygdala reactivity to faces, though within‐participant changes in amygdala reactivity could not be differentiated from between‐participant differences. In contrast, amygdala—mPFC functional connectivity results varied across methods much more, and evidence for age‐related change in amygdala—mPFC connectivity was not consistent. Generalized psychophysiological interaction (gPPI) measurements of connectivity were especially sensitive to whether a deconvolution step was applied. Our findings demonstrate the importance of assessing the robustness of findings to analysis choices, although the age‐related changes in our current work cannot be overinterpreted given low test–retest reliability. Together, these findings highlight both the challenges in estimating developmental change in longitudinal cohorts and the value of multiverse approaches in developmental neuroimaging for assessing robustness of results.

Age-related changes in CB1 receptor expression and function and the behavioral effects of cannabinoid receptor ligands

Cannabinoid use has increased among aging individuals. However, little information on age-related differences in the behavioral effects of these agents is available. To explore potential differences in the behavioral effects of cannabinoids, we determined effects of Δ9-tetrahydrocannabinol (THC, 1–10 mg/kg) or rimonabant (0.3–3.2 mg/kg) on operant fixed-ratio responding (FR10) for food in young adult (6 months) and aged (29 months) rats. THC dose-dependently decreased responding for food. Rimonabant alone had little or no effect on responding up to 1.0 mg/kg, but disrupted responding following a 3.2 mg/kg dose. Rimonabant (1.0 mg/kg) partially antagonized response disruption by THC. These effects were similar in young adult and aged rats. However, aging has been reported to change the neurobiology of cannabinoid CB1 receptors. To confirm our rats exhibited such differences, we assessed CB1 receptor binding sites and function in six subcortical (caudate, nucleus accumbens CA1, and CA2/CA3), and three cortical regions (medial prefrontal, temporal, entorhinal) in young adult (6 months) or aged (26 months) male Lewis rats using quantitative autoradiography. CB1 receptor binding sites were reduced in cortical, but not subcortical brain regions of aged rats. CB1 receptor function, at the level of receptor-G protein interaction, was not different in any region studied. Results indicate that down-regulation of CB1 receptor binding sites observed in cortical regions of aged rats was not accompanied by a commensurate decrease in CB1 receptor-stimulated [35S]GTPγS binding, suggesting a compensatory increase in receptor function in cortical areas. Together, our results provide additional evidence of age-related changes in central CB1 receptor populations. However, the functional compensation for decreased CB1 receptor binding may mitigate changes in behavioral effects of cannabinoids. With the rising use of cannabinoid-based therapeutics among aging populations, further evaluation of age-related changes in the cannabinoid system and the impact of these changes on effects of this class of drugs is warranted.

A New Method for Visualizing Drusen and Their Progression in Flood-Illumination Adaptive Optics Ophthalmoscopy.

PurposeDrusen are dynamic sub-RPE deposits that are risk factors for late-stage age-related macular degeneration (AMD). Here we show a new imaging method using flood-illumination adaptive optics (FIAO) that reveal drusen with high contrast and resolution.MethodsA fovea-centered 4° × 4° FIAO image and eight surrounding images with gaze displaced by ±2° vertically and horizontally were acquired. Clinical color fundus and spectral-domain optical coherence tomography were acquired for clinical grading and comparison. Custom software registered overlapping FIAO images and fused the data statistically to generate a fovea-centered 4° × 4° gaze-dependent image. Our dataset included 15 controls (aged 31–72) and 182 eyes from 104 AMD patients (aged 56–92), graded as either normal aging (n = 7), and early (n = 12), intermediate (n = 108) and late AMD (n = 42); 27 had subretinal drusenoid deposits (SDDs), and 83 were imaged longitudinally.ResultsNo gaze varying structures were detected in young eyes. In aging eyes with no evidence of age-related changes, putative drusen <20 µm in diameter were visible. Gaze-dependent images revealed more drusen and many smaller drusen than visible in color fundus images. Longitudinal images showed expansion and fusion of drusen. SDDs were lower contrast, and RPE atrophy did not yield a consistent signal.ConclusionsGaze-dependent imaging in a commercially available FIAO fundus camera combined with image registration and postprocessing permits visualization of drusen and their progression with high contrast and resolution.Translational RelevanceThis new technique offers promise as a robust and sensitive method to detect, map, quantify, and monitor the dynamics of drusen in aging and AMD.

Comparison of the transcriptome in circulating leukocytes in early lactation between primiparous and multiparous cows provides evidence for age-related changes

BackgroundPrevious studies have identified many immune pathways which are consistently altered in humans and model organisms as they age. Dairy cows are often culled at quite young ages due to an inability to cope adequately with metabolic and infectious diseases, resulting in reduced milk production and infertility. Improved longevity is therefore a desirable trait which would benefit both farmers and their cows. This study analysed the transcriptome derived from RNA-seq data of leukocytes obtained from Holstein cows in early lactation with respect to lactation number.ResultsSamples were divided into three lactation groups for analysis: i) primiparous (PP, n = 53), ii) multiparous in lactations 2–3 (MP 2–3, n = 121), and iii) MP in lactations 4–7 (MP > 3, n = 55). Leukocyte expression was compared between PP vs MP > 3 cows with MP 2–3 as background using DESeq2 followed by weighted gene co-expression network analysis (WGCNA). Seven modules were significantly correlated (r ≥ 0.25) to the trait lactation number. Genes from the modules which were more highly expressed in either the PP or MP > 3 cows were pooled, and the gene lists subjected to David functional annotation cluster analysis. The top three clusters from modules more highly expressed in the PP cows all involved regulation of gene transcription, particularly zinc fingers. Another cluster included genes encoding enzymes in the mitochondrial beta-oxidation pathway. Top clusters up-regulated in MP > 3 cows included the terms Glycolysis/Gluconeogenesis, C-type lectin, and Immunity. Differentially expressed candidate genes for ageing previously identified in the human blood transcriptome up-regulated in PP cows were mainly associated with T-cell function (CCR7, CD27, IL7R, CAMK4, CD28), mitochondrial ribosomal proteins (MRPS27, MRPS9, MRPS31), and DNA replication and repair (WRN). Those up-regulated in MP > 3 cows encoded immune defence proteins (LYZ, CTSZ, SREBF1, GRN, ANXA5, ADARB1).ConclusionsGenes and pathways associated with lactation number in cows were identified for the first time to date, and we found that many were comparable to those known to be associated with ageing in humans and model organisms. We also detected changes in energy utilization and immune responses in leukocytes from older cows.

A meta-analysis of fMRI studies of semantic cognition in children

Our capacity to derive meaning from things that we see and words that we hear is unparalleled in other animal species and current AI systems. Despite a wealth of functional magnetic resonance imaging (fMRI) studies on where different semantic features are processed in the adult brain, the development of these systems in children is poorly understood. Here we conducted an extensive database search and identified 50 fMRI experiments investigating semantic world knowledge, semantic relatedness judgments, and the differentiation of visual semantic object categories in children (total N = 1,018, mean age = 10.1 years, range 4–15 years). Synthesizing the results of these experiments, we found consistent activation in the bilateral inferior frontal gyri (IFG), fusiform gyri (FG), and supplementary motor areas (SMA), as well as in the left middle and superior temporal gyri (MTG/STG). Within this system, we found little evidence for age-related changes across childhood and high overlap with the adult semantic system. In sum, the identification of these cortical areas provides the starting point for further research on the mechanisms by which the developing brain learns to make sense of its environment.

Social effects on age-related and sex-specific immune cell profiles in a wild mammal.

Evidence for age-related changes in innate and adaptive immune responses is increasing in wild populations. Such changes have been linked to fitness, and knowledge of the factors driving immune response variation is important for understanding the evolution of immunity. Age-related changes in immune profiles may be owing to factors such as immune system development, sex-specific behaviour and responses to environmental conditions. Social environments may also contribute to variation in immunological responses, for example, through transmission of pathogens and stress arising from resource and mate competition. Yet, the impact of the social environment on age-related changes in immune cell profiles is currently understudied in the wild. Here, we tested the relationship between leukocyte cell composition (proportion of neutrophils and lymphocytes [innate and adaptive immunity, respectively] that were lymphocytes) and age, sex and group size in a wild population of European badgers (Meles meles). We found that the proportion of lymphocytes in early life was greater in males in smaller groups compared to larger groups, but with a faster age-related decline in smaller groups. By contrast, the proportion of lymphocytes in females was not significantly related to age or group size. Our results provide evidence of sex-specific age-related changes in immune cell profiles in a wild mammal, which are influenced by the social environment.

Monitoring type 2 diabetes from volatile faecal metabolome in Cushing\u2019s syndrome and single Afmid mouse models via a longitudinal study

The analysis of volatile organic compounds (VOCs) as a non-invasive method for disease monitoring, such as type 2 diabetes (T2D) has shown potential over the years although not yet set in clinical practice. Longitudinal studies to date are limited and the understanding of the underlying VOC emission over the age is poorly understood. This study investigated longitudinal changes in VOCs present in faecal headspace in two mouse models of T2D – Cushing’s syndrome and single Afmid knockout mice. Longitudinal changes in bodyweight, blood glucose levels and plasma insulin concentration were also reported. Faecal headspace analysis was carried out using selected ion flow tube mass spectrometry (SIFT-MS) and thermal desorption coupled to gas chromatography-mass spectrometry (TD-GC-MS). Multivariate data analysis of the VOC profile showed differences mainly in acetic acid and butyric acid able to discriminate the groups Afmid and Cushing’s mice. Moreover, multivariate data analysis revealed statistically significant differences in VOCs between Cushing’s mice/wild-type (WT) littermates, mainly short-chain fatty acids (SCFAs), ketones, and alcohols, and longitudinal differences mainly attributed to methanol, ethanol and acetone. Afmid mice did not present statistically significant differences in their volatile faecal metabolome when compared to their respective WT littermates. The findings suggested that mice developed a diabetic phenotype and that the altered VOC profile may imply a related change in gut microbiota, particularly in Cushing’s mice. Furthermore, this study provided major evidence of age-related changes on the volatile profile of diabetic mice.

Pharmacokinetics of Anticancer Drugs Used in Treatment of Older Adults With Colorectal Cancer: A Systematic Review.

Older adults with cancer experience more toxicity from anticancer therapy, possibly because of age-related changes in the pharmacokinetic (PK) profile of anticancer drugs. We aimed to evaluate studies investigating the effect of aging on the PK of anticancer therapies used in the treatment of colorectal cancer (CRC). A systematic literature search of EMBASE and PubMed was performed to find eligible studies that assessed the effect of age on the PK of anticancer therapies used in the treatment of CRC. The 21 eligible studies included 17 prospective studies and 4 pooled analyses of prospective studies. Of these, PK of 5-fluorouracil (5-FU) was determined in 7 studies, oxaliplatin in 2 studies, capecitabine in 3 studies, irinotecan in 4 studies, bevacizumab in 1 study, cetuximab in 3 studies, and panitumumab in 1 study. Studies included a median of 44 patients and had varying definitions for older adults: 65 years or older (3 studies), older than 70 years (3 studies), or older than 75 years (1 study). Increasing age significantly affected the PK parameters of irinotecan with a 7%-8% reduction in CL (P < 0.001) for every 10 years in patients older than 60 years and an increase in area under the curve (r = 0.44, P = 0.007) and Cmax (r = 0.42, P = 0.009). Older age mainly influences PK of irinotecan and, to some extent, that of capecitabine, 5-FU, and panitumumab, but there is limited evidence for age-related changes in PK of other anticancer therapies used in the management of older adults with CRC. Factors other than PK may be responsible for the greater toxicity of these agents experienced by older adults.

Ontogeny of the adrenocortical response in an extremely altricial bird.

Life history theory predicts that physiological and behavioral responsiveness to stress should be delayed in development until the benefits of heightened reactivity outweigh the costs of potentially chronic glucocorticoid levels. Birds often acquire stress-responsiveness at locomotor independence, however, both stress-responsiveness and locomotor ability are delayed in birds with altricial developmental strategies. Parrots (Psittacidae) are extremely altricial, but it is not known whether they also postpone physiological responsiveness to stress until locomotor independence. We quantified individual variation in baseline and stress-induced plasma corticosterone (CORT) concentrations, the main avian glucocorticoid, in wild green-rumped parrotlets (Forpus passerinus) of Venezuela at four stages of nestling development. Parrotlet neonates are very underdeveloped and compete for parental care among extreme sibling size hierarchies, a competitive scenario that might benefit from early hypothalamic-pituitary-adrenal (HPA) functionality. Nestlings that underwent a standardized restraint stress-treatment showed higher average CORT concentrations compared to baseline in all age groups sampled, and exhibited no evidence of age-related changes in the stress response. This is 2 weeks before locomotor independence and earlier than previously documented for altricial species. Results suggest that precocity of HPA function may be advantageous to growth and survivorship in extremely altricial birds.

Musical playschool activities are linked to faster auditory development during preschool-age: a longitudinal ERP study

The influence of musical experience on brain development has been mostly studied in school-aged children with formal musical training while little is known about the possible effects of less formal musical activities typical for preschool-aged children (e.g., before the age of seven). In the current study, we investigated whether the amount of musical group activities is reflected in the maturation of neural sound discrimination from toddler to preschool-age. Specifically, we recorded event-related potentials longitudinally (84 recordings from 33 children) in a mismatch negativity (MMN) paradigm to different musically relevant sound changes at ages 2–3, 4–5 and 6–7 years from children who attended a musical playschool throughout the follow-up period and children with shorter attendance to the same playschool. In the first group, we found a gradual positive to negative shift in the polarities of the mismatch responses while the latter group showed little evidence of age-related changes in neural sound discrimination. The current study indicates that the maturation of sound encoding indexed by the MMN may be more protracted than once thought and provides first longitudinal evidence that even quite informal musical group activities facilitate the development of neural sound discrimination during early childhood.

Immunosenescence in wild animals: meta-analysis and outlook.

Immunosenescence, the decline in immune defense with age, is an important mortality source in elderly humans but little is known of immunosenescence in wild animals. We systematically reviewed and meta-analysed evidence for age-related changes in immunity in captive and free-living populations of wild species (321 effect sizes in 62 studies across 44 species of mammals, birds and reptiles). As in humans, senescence was more evident in adaptive (acquired) than innate immune functions. Declines were evident for cell function (antibody response), the relative abundance of naïve immune cells and an in vivo measure of overall immune responsiveness (local response to phytohaemagglutinin injection). Inflammatory markers increased with age, similar to chronic inflammation associated with human immunosenescence. Comparisons across taxa and captive vs free-living animals were difficult due to lack of overlap in parameters and species measured. Most studies are cross-sectional, which yields biased estimates of age-effects when immune function co-varies with survival. We therefore suggest longitudinal sampling approaches, and highlight techniques from human cohort studies that can be incorporated into ecological research. We also identify avenues to address predictions from evolutionary theory and the contribution of immunosenescence to age-related increases in disease susceptibility and mortality.

Meta-analyses of the n-back working memory task: fMRI evidence of age-related changes in prefrontal cortex involvement across the adult lifespan

Working memory, a fundamental cognitive function that is highly dependent on the integrity of the prefrontal cortex, is known to show age-related decline across the typical healthy adult lifespan. Moreover, we know from work in neurophysiology that the prefrontal cortex is disproportionately susceptibly to the pathological effects of aging. The n-back task is arguably the most ubiquitous cognitive task for investigating working memory performance. Many functional magnetic resonance imaging (fMRI) studies examine brain regions engaged during performance of the n-back task in adults. The current meta-analyses are the first to examine concordance and age-related changes across the healthy adult lifespan in brain areas engaged when performing the n-back task. We compile data from eligible fMRI articles that report stereotaxic coordinates of brain activity from healthy adults in three age-groups: young (23.57 ± 5.63 years), middle-aged (38.13 ± 5.63 years) and older (66.86 ± 5.70 years) adults. Findings show that the three groups share concordance in the engagement of parietal and cingulate cortices, which have been consistently identified as core areas involved in working memory; as well as the insula, claustrum, and cerebellum, which have not been highlighted as areas involved in working memory. Critically, prefrontal cortex engagement is concordant for young, to a lesser degree for middle-aged adults, and absent in older adults, suggesting a gradual linear decline in concordance of prefrontal cortex engagement. Our results provide important new knowledge for improving methodology and theories of cognition across the lifespan.

Evidence for age-related changes in sensorimotor neuromagnetic responses during cued button pressing in a large open-access dataset

Mu, beta, and gamma rhythms increase and decrease in amplitude during movement. This event-related synchronization (ERS) and desynchronization (ERD) can be readily recorded non-invasively using magneto- and electro-encephalography (M/EEG). In addition, event-related potentials and fields (i.e., evoked responses) can be elucidated during movement. There is some evidence that the frequency, amplitude and latency of the movement-related ERS/ERD changes with ageing, however the evidence surrounding this topic comes mainly from studies in sample sizes on the order of tens of participants. The objective of this study was to examine a large open-access MEG dataset for age-related changes in movement-related ERS/ERD and evoked responses. MEG data acquired at the Cambridge Centre for Ageing and Neuroscience during cued button pressing was used from 567 participants between the ages of 18 and 88 years. The characteristics movement-related ERD/ERS and evoked responses were calculated for each individual participant. Based on linear regression analysis, significant relationships were found between participant age and some response characteristics, although the predictive value of these relationships was low. Specifically, we conclude that peak beta rebound frequency and amplitude decreased with age, peak beta suppression amplitude increased with age, movement-related gamma burst amplitude decreased with age, and peak motor-evoked response amplitude increased with age. Given our current understanding of the underlying mechanisms of these responses, our findings suggest the existence of age-related changes in the neurophysiology of thalamocortical loops and local circuitry in the primary somatosensory and motor cortices.

Evidence of age-related improvement in the foraging efficiency of Ad\xe9lie penguins

Age variation in reproductive performance is well-documented but the mechanisms underlying this variation remain unclear. Foraging efficiency is likely to be a key source of demographic variation as it determines the amount of energy that can be invested in fitness-related activities. Evidence of age-related changes in the foraging efficiency of adult seabirds is scarce and inconsistent. We investigated the effects of age on the foraging efficiency of breeding Adélie penguins, a relatively short-lived seabird species, in order to gain a broader perspective on the processes driving variation in ageing rates. We found support for a positive effect of age, either linear or levelling off at old ages, on both our proxies for daily catch rate and catch per unit effort. Across all age classes, males were more performant foragers than females. We found no strong evidence for differing ageing patterns between sexes or individual quality levels, and no evidence for senescence. We infer that continuous individual improvement could be responsible for a larger amount of the variation in foraging efficiency with age at our study site, compared with selective disappearance of underperforming phenotypes. The different results reported by other studies highlight the need to conduct longitudinal studies across a range of species in different environments.

Are age-related changes in cortical motor representations linked with facilitation/inhibition in the primary motor cortex?

Are age-related changes in cortical motor representations linked with facilitation/inhibition in the primary motor cortex?

Declining home range area predicts reduced late-life survival in two wild ungulate populations.

Demographic senescence is increasingly recognised as an important force shaping the dynamics of wild vertebrate populations. However, our understanding of the processes that underpin these declines in survival and fertility in old age remains limited. Evidence for age-related changes in foraging behaviour and habitat use is emerging from wild vertebrate studies, but the extent to which these are driven by within-individual changes, and the consequences for fitness, remain unclear. Using longitudinal census observations collected over four decades from two long-term individual-based studies of unmanaged ungulates, we demonstrate consistent within-individual declines in home range area with age in adult females. In both systems, we found that within-individual decreases in home range area were associated with increased risk of mortality the following year. Our results provide the first evidence from the wild that age-related changes in space use are predictive of adult mortality.