Age Trajectories Research Articles

Childhood BMI trajectories and sociodemographic factors in an Italian pediatric population

Childhood obesity is a growing global concern due to its long-term health consequences. Yet, more research relying on multiple time-point BMI measurements is warranted to gain further insight into obesity’s temporal trends. We aimed to identify BMI trajectories in children aged 2–10 years and evaluate their association with sociodemographic factors. This retrospective cohort study utilized data from the PEDIANET registry, containing sociodemographic, clinical, and prescribing information on patients assisted by Italian family pediatricians, linked to the corresponding area deprivation index. 29,576 children with at least 10 years of follow-up, born at term with normal birthweight, and at least three plausible BMI measurements were identified. BMI z-score trajectories were calculated using Group-Based Trajectory Modeling, and mixed multinomial logistic regression was used to assess their association with the sociodemographic factors. A secondary analysis examined BMI trajectories from ages 2–7 years (n = 58,509). Four BMI z-scores trajectories, all with quadratic shape, were identified as the optimal fit: “stable-low-weight” (27.5%), “normal-weight” (40.9%), “stable-moderate-increase” (24.2%), and “overweight-to-obese” (7.5%). Females, children residing in Southern and Island regions, and those from more deprived socioeconomic areas had a higher probability of following the “overweight-to-obese” group compared to the “normal-weight” trajectory. Sex and area of residence had similar effects on the “stable-moderate-increase” trajectory. Conversely, females and children residing in Central Italy were less likely to belong to the “stable-low-weight trajectory”. This study highlighted a considerable heterogeneity in BMI trajectories in pediatric age, emphasizing the effect of sociodemographic inequalities on growth patterns with models capable of capturing the dynamic nature of the phenomenon.

Activated SKN-1 alters the aging trajectories of long-lived C. elegans mutants.

In the presence of stressful environments, the SKN-1 cytoprotective transcription factor is activated to induce the expression of gene targets that can restore homeostasis. However, chronic activation of SKN-1 results in diminished health and a reduction of lifespan. Here we demonstrate the necessity of modulating SKN-1 activity to maintain the longevity-promoting effects associated with genetic mutations that impair daf-2/insulin receptor signaling, the eat-2 model of dietary restriction, and glp-1-dependent loss of germ cell proliferation. A hallmark of animals with constitutive SKN-1 activation is the age-dependent loss of somatic lipids and this phenotype is linked to a general reduction in survival in animals harboring the skn-1gf allele. Surprisingly, daf-2lf; skn-1gf double mutant animals do not redistribute somatic lipids, which suggests the insulin signaling pathway functions downstream of SKN-1 in the maintenance of lipid distribution. As expected, the eat-2lf allele, which independently activates SKN-1, continues to display somatic lipid depletion in older ages with and without the skn-1gf activating mutation. In contrast, the presence of the skn-1gf allele does not lead to somatic lipid redistribution in glp-1lf animals that lack a proliferating germline. Taken together, these studies support a genetic model where SKN-1 activity is an important regulator of lipid mobilization in response to nutrient availability that fuels the developing germline by engaging the daf-2/insulin receptor pathway.

Modifiable risk factors for cognitive decline in community-dwelling older adults differ by sex and APOE4.

The extent to which lifestyle shapes trajectories of normal cognitive aging, and the factors with highest potential for mitigating cognitive decline, remain poorly uncharacterized. Participants of the Rancho Bernardo Study underwent demographic, health, and behavioral characterization at baseline, along with up to seven cognitive assessments over a 27-year follow-up period. Factor analysis of 24 baseline risk variables identified 9 composite factors. Mixed effects models on data from 1489 participants (aged 45-95 years at baseline) assessed prediction of cognitive change by baseline factor scores. Models were repeated stratified by sex and APOE4 status. Factors of hyperlipidemia and obesity; marriage and depression; occupation and education; and physical activity and subjective health best predicted rates of decline across multiple cognitive domains. Distinct risk profiles were identified for women and men, and for APOE4 carriers and non-carriers. Models of composite risk estimated that potential savings could amount to 7-9.5 years of preserved cognitive healthspan for low- versus high-risk profiles. Magnitudes of aggregate risk effects were greater among women across cognitive domains, and for APOE4 carriers for memory and verbal fluency. Multifactorial life-course approaches to manage cardiometabolic health and promote physical, cognitive, and social engagement, may help to mitigate cognitive decline with age, with composite risk associated with up to a decade of preserved cognitive health-span. Differences by sex and APOE4 in risk profiles and their potential for risk reduction, highlight the importance of developing personalized recommendations for multi-domain approaches to cognitive health maintenance throughout the life-course.

Analysis of sex-specific disease patterns associated with human lifespan.

Disability and multimorbidity increase with aging and constitute a challenge for the health system. However, different individuals display different aging trajectories, and understanding the underlying relationships between lifespan and disease is fundamental for identifying the different patterns in human lifespan. A previous study explored associations between lifespan and age of onset of diseases of different organ systems, prevalence of escapers, and percentage of life free of disease (health span), comparing them between genders in Catalonian population. In this retrospective study, we analyzed a cohort of 41,063 old individuals (20,722 men, with a mean lifespan of 79years [50-109], and 20,341 women, with a mean lifespan of 84years [50-109]) deceased between 2014 and 2019 in Gipuzkoa (Basque Country, Spain) taken from the Basque Health Service electronic health records data lake and analyzed and contrasted the above cited characteristics. Longevity, defined by age above the mean lifespan of the population, showed a protective effect against developing diseases, with higher lifespans delaying the onset of all diseases both at single and multisystemic levels. Furthermore, individuals with the lowest and highest lifespans were the ones presenting the healthier profiles, with fewer systems altered. There were specific differences according to sex, with women exhibiting decreased mortality risk despite having greater multimorbidity and men having less multimorbidity. In addition, men reached the highest lifespans with a smaller number of comorbidities. These results define the aging trajectories of the Basque population, extend the characterization of the human aging, and provide insight into sex-specific differences in multimorbidity and survival risk.

Mid-life: a critical window for intervention during aging

Mid-life represents a pivotal period marked by profound physiological and metabolic transitions, increasing susceptibility to chronic diseases. This review explores the molecular and systemic underpinnings of mid-life transition by integrating insights from recent studies that elucidate aging-associated changes in the plasma proteome, immune system, adipose tissue remodeling, and cellular senescence. Nonlinear waves of proteomic alterations have been identified as critical mid-life transitions in inflammatory and hormonal pathways. In addition, sex-specific immune aging trajectories have linked adaptive immunity decline and innate immune activation to metabolic vulnerabilities in mid-life. Moreover, adipose tissue’s central role has been established in mid-life transitions as its early remodeling and inflammatory cytokine secretion drive the systemic aging and metabolic stress. Furthermore, Glb1-2A-mCherry reporter has been introduced to monitor systemic aging, identifying mid-life as a crucial phase for cardiac hypertrophy and senescence-induced inflammation. Collectively, these findings have established our understanding of mid-life transitions, underscoring the interplay between aging processes and metabolic health, with mid-life emerging as a critical window for intervention. This review also underscores biomarkers and therapeutic strategies to alleviate the metabolic challenges of mid-life, thereby promoting healthy aging.

Participation as a Pillar of Active Ageing: The Role of Eudaimonic Psychological and Health Factors.

Background/Objectives: With ageing population projections, promoting positive ageing trajectories is critical. While health is often emphasised, eudaimonic psychological factors remain underexamined. A qualitative study presented throughout the main text highlighted the importance of psychological factors like purpose in life and resilience in fostering participation and subjective well-being, even amidst declining health. This model bridges the most recent updates from governmental organisations-the International Longevity Center, Brazil and the World Health Organization. Building on this model, the current research seeks to empirically assess the impact of health and eudaimonic psychological factors on the frequency and satisfaction of participation among older adults. Methods: This study involved 289 participants (56.74% women) aged 65+ in Madrid. Data on participation, self-perceived health, and eudaimonic factors were collected through an online survey. Hierarchical regression and cluster analyses explored the predictors and profiles of participation. Results: Resilience, positive relationships, and autonomy explained 8.8% of variance in participation frequency. Satisfaction was influenced by health, meaning in life, and autonomy, accounting for 11% of variance. Profiles showed the highest participation and satisfaction in individuals with high eudaimonic scores, despite moderate health. Conclusions: Eudaimonic factors significantly influence participation and mitigate health limitations, reinforcing the qualitative study model mentioned. By uniting updates from governmental organisations proposals, this model underscores the role of psychological well-being in active ageing. Future research should explore hedonic well-being as a key outcome of active ageing.

Sex and education differences in trajectories of physiological ageing: longitudinal analysis of a prospective English cohort study.

Physiological age (PA) derived from clinical indicators including blood-based biomarkers and tests of physiological function can be compared with chronological age to examine disparities in health between older adults of the same age. Though education interacts with sex to lead to inequalities in healthy ageing, their combined influence on longitudinally-measured PA has not been explored. We derived PA based on longitudinally-measured clinical indicators and examined how sex and education interact to inform PA trajectories. Three waves of clinical indicators (2004/05-2012/13) drawn from the English Longitudinal Study of Ageing (ages 50-100 years) were used to estimate PA, which was internally validated by confirming associations with incident chronic conditions, functional limitations, and memory impairment after adjustment for chronological age and sex. Joint models were used to construct PA trajectories in 8,891 ELSA participants to examine sex and educational disparities in PA. Among the least educated participants, there were negligible sex differences in PA until age 60 (sex difference [men-women] age 50=-0.6 years [95% confidence interval=-2.2-0.6]; age 60=0.4 [-0.6-1.4]); at age 70, women were 1.5 years (0.7-2.2) older than men. Among the most educated participants, women were 3.8 years (1.6-6.0) younger than men at age 50, and 2.7 years (0.4-5.0) younger at age 60, with a non-significant sex difference at age 70. Higher education provides a larger midlife buffer to physiological ageing for women than men. Policies to promote gender equity in higher education may contribute to improving women's health across a range of ageing-related outcomes.

Appetite-related Gut Hormone Responses to Feeding Across the Life Course.

Appetite-related hormones are secreted from the gut, signaling the presence of nutrients. Such signaling allows for cross-talk between the gut and the appetite-control regions of the brain, influencing appetite and food intake. As nutritional requirements change throughout the life course, it is perhaps unsurprising that appetite and eating behavior are not constant. Changes in appetite-related gut hormones may underpin these alterations in appetite and eating. In this article, we review evidence of how the release of appetite-related gut hormones changes throughout the life course and how this impacts appetite and eating behaviour. We focus on hormones for which there is the strongest evidence of impact on appetite, food intake, and body weight: the anorexigenic glucagon like peptide-1, peptide tyrosine tyrosine, and cholecystokinin, and the orexigenic ghrelin. We consider hormone concentrations, particularly in response to feeding, from the very early days of life, through childhood and adolescence, where responses may reflect energy requirements to support growth and development. We discuss the period of adulthood and midlife, with a particular focus on sex differences and the effect of menstruation, pregnancy, and menopause, as well as the potential influence of appetite-related gut hormones on body composition and weight status. We then discuss recent advancements in our understanding of how unfavorable changes in appetite-related gut hormone responses to feeding in later life may contribute to undernutrition and a detrimental aging trajectory. Finally, we briefly highlight priorities for future research.

Weight trajectories in aging humanized APOE mice with translational validity to human Alzheimer's risk population: A retrospective analysis.

Translational validity of mouse models of Alzheimer's disease (AD) is variable. Because change in weight is a well-documented precursor of AD, we investigated whether diversity of human AD risk weight phenotypes was evident in a longitudinally characterized cohort of 1,196 female and male humanized APOE (hAPOE) mice, monitored up to 28 months of age which is equivalent to 81 human years. Autoregressive Hidden Markov Model (AHMM) incorporating age, sex, and APOE genotype was employed to identify emergent weight trajectories and phenotypes. In the hAPOE-AD mouse cohort, five distinct weight trajectories emerged: three trajectories were associated with a weight loss phenotype (36% of mice, n = 426), one with weight gain (13% of mice, n = 152), and one trajectory of no change in weight (34% of mice, n = 403). The AHMM model findings were validated with post-hoc survival analyses, revealing differences in survival rates across the five identified phenotypes. Further validation was performed using body composition and plasma β-amyloid data from mice within the identified gain, loss and stable weight trajectories. Weight gain trajectory was associated with elevated plasma β-amyloid levels, higher body fat composition, lower survival rates and a greater proportion of APOE4/4 carriers. In contrast, weight loss was associated with greater proportion of hAPOE3/4 carriers, better survival rates and was predominantly male. The association between weight change and AD risk observed in humans was mirrored in the hAPOE-AD mouse model. Weight trajectories of APOE3/3 mice were equally distributed across weight gain, loss and stability. Surprisingly, despite genetic uniformity, comparable housing, diet and handling, distinct weight trajectories and divergence points emerged for subpopulations. These data are consistent with the heterogeneity observed in the human population for change in body weight during aging and highlight the importance of longitudinal phenotypic characterization of mouse aging to advance the translational validity of preclinical AD mouse models.

Age-friendly community environments and the age trajectories of long-term care dependency among Chinese older adults.

In the context of rapid global aging, the importance of age-friendly community environments for promoting healthy aging and "aging in place" continues to increase. Using data from the 2011-2020 China Health and Retirement Longitudinal Study, this study investigated the impact of an age-friendly community environment on the age trajectories of late-life long-term care (LTC) dependency among older Chinese adults aged 60+ years. Age-friendly community environments were defined according to three levels (poor, moderate, or good) based on the World Health Organization's age-friendly city and community framework, and LTC dependency was classified as level 1 (high), level 2 (medium), or level 3 (low) according to activities of daily living and instrumental activities of daily living scores. We classified participants into two age trajectory groups according to their level of LTC dependency: early-onset and late-onset groups. We found that an age-friendly community environment, especially a good housing environment, was consistently associated with the probability of having late-onset LTC dependency at any level. Having moderate and good social and employment environments reduced the likelihood of having early-onset level 2 and level 3 LTC dependency. Our mechanism analysis also revealed that age-friendly community environments affect LTC dependency through social participation. Our results may help elucidate the importance of promoting age-friendly community environments to maintain late-life functional ability and support healthy aging.

Maternal social isolation during pre-conception and pregnancy programs inflammatory markers and biobehavioural aging trajectories in distant F4 offspring

Maternal social isolation during pre-conception and pregnancy programs inflammatory markers and biobehavioural aging trajectories in distant F4 offspring

The development of social attention in orangutans: Comparing peering behavior in wild and zoo-housed individuals.

Social learning plays an essential role in all cultural processes, but the factors underlying its evolution remain poorly understood. To understand how socio-ecological conditions affect social learning, we compared peering behavior (i.e., close-range observation of conspecifics' activities) in wild and zoo-housed Sumatran orangutans. Using long-term data describing over 3,000 peering events (performed by 65 individuals across settings), we found similar age trajectories of peering in both settings. Moreover, immatures universally preferred to peer at older individuals and in learning-intense contexts. However, zoo-housed immatures peered more frequently, and more at non-mother individuals than their wild conspecifics, even when social opportunities were controlled for. Therefore, although similarities across settings suggest that the tendency to attend to social information has hard-wired components, the differences indicate that it is also influenced by social opportunities and the necessity to learn. Our comparative approach thus provides evidence that socio-ecological factors and genetic predispositions underlie the dynamics and evolution of culture.

Static and dynamic connectivity structure of white-matter functional networks across the adult lifespan.

Aging of the human brain involves intricate biological processes, resulting in complex changes in structure and function. While the effects of aging on gray matter (GM) connectivity are extensively studied, white matter (WM) functional changes have received comparatively less attention. This study examines age-related WM functional dynamics using resting-state fMRI across the adult lifespan. We identified GM and WM functional networks (FNs) using k-means clustering. Static and dynamic analyses of WM functional network connectivity (FNC) were performed to explore age effects on WM-FNs and recurrent patterns of dynamic FNC. We identified 9 WM and 12 GM FNs. Age-related effects on WM FNC strength and WM-GM FNC dynamics included linear positive and U-shaped age trajectories in static FNC strength, and linear negative and inverted U-shaped trajectories in FNC temporal variability. Three distinct brain states with significant age-related differences were identified and validated. These findings were largely replicated in the validation analysis. High integration and low temporal variability in WM-GM FNC may indicate reduced adaptability of the network system in older adults, offering insights into brain aging processes.

Female reproductive ageing persists despite high infanticide risk in chacma baboons and geladas.

Across mammals, fertility and offspring survival are often lowest at the beginning and end of females' reproductive careers. However, extrinsic drivers of reproductive success-including infanticide by males-could stochastically obscure these expected age-related trends. Here, we modelled reproductive ageing trajectories in two cercopithecine primates that experience high rates of male infanticide: the chacma baboon (Papio ursinus) and the gelada (Theropithecus gelada). We found that middle-aged mothers generally achieved the shortest interbirth intervals in chacma baboons. By contrast, old gelada females often showed shorter interbirth intervals than their younger group-mates with one exception: the oldest females typically failed to produce additional offspring before their deaths. Infant survival peaked in middle-aged mothers in chacma baboons but in young mothers in geladas. While infant mortality linked with maternal death increased as mothers aged in both species, infanticide risk did not predictably shift with maternal age. Thus, infanticide patterns cannot explain the surprising young mother advantage observed in geladas. Instead, we argue that this could be a product of their graminivorous diets, which might remove some energetic constraints on early reproduction. In sum, our data suggest that reproductive ageing is widespread but may be differentially shaped by ecological pressures.

Diffusion time effects over the adult lifespan indicates persistent zone-specific microstructural alterations in the human prostate with aging.

The purpose of this study was to investigate microstructural changes in the aging adult prostate by comparing the effects of varying diffusion times using diffusion MRI, and to provide an age-related benchmark for future prostate cancer studies. The prostates of normal male volunteers (n = 70, 19-69 years) were scanned at 3 T with an oscillating gradient spin echo (OGSE: 6 ms), pulsed gradient spin echo (PGSE: 40 ms) and pulsed gradient stimulated echo (PGSTE: 100 ms), and anatomical T2-weighted image. Volume and mean diffusivity (MD) were measured in the peripheral (PZ) and transition zones (TZ), which were assessed versus age. PZ and TZ showed quadratic age trajectories for all diffusion scans, with MD decreasing from 19 years to a minimum ˜30-40 years followed by a greater increase at older ages. Short (OGSE) and medium (PGSE) diffusion time MD had similar age trajectories, whereas long diffusion time (PGSTE) MD was significantly lower, particularly in PZ (22%). MD difference (∆MD) of OGSE-PGSTE and PGSE-PGSTE showed significant positive linear correlations with age for both PZ (larger slope) and TZ, resulting in ˜3.3x (PZ) and 1.8x (TZ) greater ∆MD from 19 to 69 years. MD and ∆MD versus age relationships differed from volume, which conversely had greater proportional growth in TZ than PZ. The diffusion time effects suggest age-related microstructural changes consistent with development of persistently larger cell dimensions mainly in the prostate peripheral zone over the adult lifespan. This normative data can be used for comparison to prostate cancer factoring in age.

Predicting host health status through an integrated machine learning framework: insights from healthy gut microbiome aging trajectory

The gut microbiome, recognized as a critical component in the development of chronic diseases and aging processes, constitutes a promising approach for predicting host health status. Previous research has underscored the potential of microbiome-based predictions, and the rapid advancements of machine learning techniques have introduced new opportunities for exploiting microbiome data. To predict various host nonhealthy conditions, this study proposed an integrated machine learning-based estimation pipeline of Gut Age Index (GAI) by establishing a health aging baseline with the gut microbiome data from healthy individuals. We assessed the performance of GAI pipeline on two extensive cohorts - the Guangdong Gut Microbiome Project (GGMP) and the American Gut Project (AGP). In the GGMP cohort, for 20 common chronic diseases such as metabolic syndrome, obesity, and cardiovascular diseases, the proposed GAI achieved a balanced accuracy, ranging from 66 to 75%, with the prediction performance for atherosclerosis being the highest. In the AGP cohort, the balanced accuracy of GAI ranged from 58 to 72% for 10 diseases. Based on the results from these two datasets, we conclude that our proposed approach in this study can be used to predict individual health status, which offers the potential for scalable, cost-effective, and personalized health insights.

Sex differences in allostatic load trajectories among midlife and older adults: Evidence from the China health and retirement longitudinal study.

The female advantage in life expectancy sits uneasily with female disadvantage in health and well-being in later life compared to their male counterparts. This health disparity has been suggested to rest on sex difference in allostatic load (AL). We aim to delineate the sex-specific age trajectories of AL among midlife and older adults in China and to interpret the contradiction between the female advantage in life expectancy and their disadvantage in health in later life from the perspective of physiological dysregulation. Using data from the China Health and Retirement Longitudinal Study (CHARLS) conducted in 2011 and 2015, we included 3,836 male and 3,308 female Chinese adults aged 45 and older. Two-level mixed-effects models were fitted to examine how AL changed over time. Missing values were addressed by performing multiple imputations using chained equations. Results show AL increases with age for both sexes, with a steeper rise in females and a slight decline in males after adjusting for the sex-age interaction. Older males born before the People's Republic of China (PRC) exhibited different AL trajectories from younger cohorts. The sex-specific trajectories converge around the late 60s, with females surpassing males, aligning with the life expectancy-health paradox. The presence of a healthier older male cohort in CHARLS suggests future studies should account for cohort effects.

Loneliness in older persons with schizophrenia.

In tandem with the rise in numbers of older adults in the general population, more people with schizophrenia (PwS) are also living longer. This vulnerable population has several trajectories of ageing driven by a number of social determinants of health, including the experience of loneliness and they may be more at risk of experiencing loneliness. This study aimed to examine demographic, psychosocial and clinical variables and their relative contribution to the loneliness of older PwS (OPwS) in a large New Zealand community sample. New Zealanders 65 years and older who completed their first interRAI assessment during the study period were included. Data from 1,883 OPwS participants was analysed [mean age, 75.1 + 7.7 years; 1,132 (60.3%) females]. The majority were of European ethnicity (64.8%; Māori 15.7%, Pacifica 5.7%) and only a minority were married (20.6%). Chi-square analysis was used to examine relationships between loneliness and demographic and psychosocial variables. Logistic regression was used to measure the relative contribution of these variables to loneliness. Being lonely was reported for 25.9% of OPwS, a significantly higher rate than that reported in the general population of people over 65 years-of-age. A relationship with loneliness was found for marital status, depression and living arrangements but not gender, ethnicity or social engagement. Co-morbid depression and not being in a marital-type partnership were identified as significant predictors of being lonely. Conversely, living with someone predicted being not lonely. Older community dwelling PwS experience higher rates of loneliness than older adults in a general population. Addressing loneliness, as well as its correlates, co-morbid depressive symptoms and living arrangements, is crucial to supporting the wellbeing of OPwS.

Mitochondrial respiration atlas reveals differential changes in mitochondrial function across sex and age

Organ function declines with age, and large-scale transcriptomic analyses have highlighted differential aging trajectories across tissues. The mechanism underlying shared and organ-selective functional changes across the lifespan, however, still remains poorly understood. Given the central role of mitochondria in powering cellular processes needed to maintain tissue health, we therefore undertook a systematic assessment of respiratory activity across 33 different tissues in young (2.5 months) and old (20 months) mice of both sexes. Our high-resolution mitochondrial respiration atlas reveals: (1) within any group of mice, mitochondrial activity varies widely across tissues, with the highest values consistently seen in heart, brown fat, and kidney; (2) biological sex is a significant but minor contributor to mitochondrial respiration, and its contributions are tissue-specific, with major differences seen in the pancreas, stomach, and white adipose tissue; (3) age is a dominant factor affecting mitochondrial activity, especially across most brain regions, different fat depots, skeletal muscle groups, eyes, and different regions of the gastrointestinal tract; (4) age effects can be sex- and tissue-specific, with some of the largest effects seen in pancreas, heart, adipose tissue, and skeletal muscle; and (5) while aging alters the functional trajectories of mitochondria in a majority of tissues, some are remarkably resilient to age-induced changes. Altogether, our data provide the most comprehensive compendium of mitochondrial respiration and illuminate functional signatures of aging across diverse tissues and organ systems.

Mitochondrial respiration atlas reveals differential changes in mitochondrial function across sex and age.

Organ function declines with age, and large-scale transcriptomic analyses have highlighted differential aging trajectories across tissues. The mechanism underlying shared and organ-selective functional changes across the lifespan, however, still remains poorly understood. Given the central role of mitochondria in powering cellular processes needed to maintain tissue health, we therefore undertook a systematic assessment of respiratory activity across 33 different tissues in young (2.5 months) and old (20 months) mice of both sexes. Our high-resolution mitochondrial respiration atlas reveals: (1) within any group of mice, mitochondrial activity varies widely across tissues, with the highest values consistently seen in heart, brown fat, and kidney; (2) biological sex is a significant but minor contributor to mitochondrial respiration, and its contributions are tissue-specific, with major differences seen in the pancreas, stomach, and white adipose tissue; (3) age is a dominant factor affecting mitochondrial activity, especially across most brain regions, different fat depots, skeletal muscle groups, eyes, and different regions of the gastrointestinal tract; (4) age effects can be sex- and tissue-specific, with some of the largest effects seen in pancreas, heart, adipose tissue, and skeletal muscle; and (5) while aging alters the functional trajectories of mitochondria in a majority of tissues, some are remarkably resilient to age-induced changes. Altogether, our data provide the most comprehensive compendium of mitochondrial respiration and illuminate functional signatures of aging across diverse tissues and organ systems.