Cross-sectional and longitudinal analysis of health-related quality of life (HRQoL) in senior and geriatric dogs.

Advancements in veterinary medicine have resulted in increased life spans for dogs, necessitating a better understanding of quality of life for older dogs. This study aimed to evaluate quality of life (QoL) progression and its potential association with mortality in senior and geriatric dogs. The Canine Owner-Reported Quality of Life Questionnaire (CORQ), consisting of 17 questions across four domains (vitality, companionship, pain, and mobility) was employed. Higher scores indicated better quality of life, with 7 as the highest potential score for each question. In a cross-sectional analysis including 92 dogs, we found an inverse correlation between overall CORQ (and all domain scores) and fractional lifespan. The domain of vitality demonstrated the lowest scores, while companionship exhibited the highest. A longitudinal analysis, including 34 dogs, revealed that when dogs reach the geriatric stage (100% of their calculated lifespan), their expected overall CORQ is 5.95 out of 7, and dogs are expected to have a monthly decline of 0.05 units in the score. Cox proportional hazard analysis demonstrated a significant association between overall CORQ scores and mortality, with dogs scoring below 5.35 being at a higher risk of mortality. This study underscores the association between aging, declining quality of life, and increased mortality risk in aging dogs.

The cell rejuvenation atlas: leveraging network biology to identify master regulators of rejuvenation strategies.

Current rejuvenation strategies, which range from calorie restriction to in vivo partial reprogramming, only improve a few specific cellular processes. In addition, the molecular mechanisms underlying these approaches are largely unknown, which hinders the design of more holistic cellular rejuvenation strategies. To address this issue, we developed SINGULAR (Single-cell RNA-seq Investigation of Rejuvenation Agents and Longevity), a cell rejuvenation atlas that provides a unified system biology analysis of diverse rejuvenation strategies across multiple organs at single-cell resolution. In particular, we leverage network biology approaches to characterize and compare the effects of each strategy at the level of intracellular signaling, cell-cell communication, and transcriptional regulation. As a result, we identified master regulators orchestrating the rejuvenation response and propose that targeting a combination of them leads to a more holistic improvement of age-dysregulated cellular processes. Thus, the interactive database accompanying SINGULAR is expected to facilitate the future design of synthetic rejuvenation interventions.

Longitudinal activity monitoring and lifespan: quantifying the interface.

Understanding the relationship between activity over the entire lifespan and longevity is an important facet of aging research. We present a comprehensive framework for the statistical analysis of longitudinal activity and behavioral monitoring and their relationship with age-at-death at the individual level, highlighting the importance of advanced methodological approaches in aging research. The focus is on animal models, where continuous monitoring activity in terms of movement, reproduction and behaviors over the entire lifespan is feasible at the individual level. We specifically demonstrate the methodology with data on activity monitoring for Mediterranean fruit flies. Advanced statistical methodologies to explore the interface between activity and age-at-death include functional principal component analysis, concurrent regression, Fréchet regression and point processes. While the focus of this perspective is on relating age-at-death with data on movement, reproduction, behavior and nutrition of Mediterranean fruit flies, the methodology equally pertains to data from other species, including human data.

The metabolic and endocrine impact of diet-derived gut microbiota metabolites on ageing and longevity.

Gut dysbiosis has been recently recognized as a hallmark of ageing. At this stage of life, gut microbiota becomes depleted from bacteria involved in the production of short-chain fatty acids (SCFA), indole and its derivative indole-3-propionic acid (IPA), metabolites shown to improve host glycemic control as well as insulin sensitivity and secretion. Moreover, gut microbiota becomes enriched in pathobiont bacteria involved in the production of imidazole propionate, phenols and trimethylamine, metabolites that promote host insulin resistance and atherosclerosis. The magnitude of these changes is much more pronounced in unhealthy than in healthy ageing. On the other hand, a distinct gut microbiota signature is displayed during longevity, the most prominent being an enrichment in both SCFA and IPA bacterial producers. This short Review discusses, in an innovative and integrative way, cutting-edge research on the composition of gut microorganisms and profile of metabolites secreted by them, that are associated with a healthy and unhealthy ageing pattern and with longevity. A detailed description of the positive or detrimental metabolic effects, in the ageing host, of diet-derived gut microbial metabolites is provided. Finally, microbiota-targeted interventions that counteract gut dysbiosis associated with ageing, are briefly outlined.

Association between change in heart rate over years and life span in the Paris Prospective 1, the Whitehall 1, and Framingham studies.

Heart rate, a measure of the frequency of the cardiac cycle, reflects the health of the cardiovascular system, metabolic rate, and activity of the autonomic nervous system. Whether changes in resting heart rate are related to lifespan has not yet been explored to our best knowledge. In this study, we examined the association between resting heart rate and lifespan using linear regression in the Paris Prospective Study I, the Whitehall I Study, and the Framingham Heart Study. We used Cox proportional hazards regression to relate changes in heart rate over years to mortality risk. We observed a statistically significant association between increases in resting heart rate over a 5-year period and risk of mortality in the Paris Prospective Study I (HR mortality per 10 bpm increase over time: 1.20; 95% CI: 1.13 to 1.27) and over an 8-year period in the Framingham Heart Study (HR: 1.13; 95% CI: 1.07 to 1.19 for men and HR: 1.09; 95% CI: 1.04 to 1.15 for women), after adjusting for classical risk factors and resting heart rate. Our study shows that men and women who increase their resting heart rate over time increase their risk of mortality.

Enhanced cellular longevity arising from environmental fluctuations.

Cellular longevity is regulated by both genetic and environmental factors. However, the interactions of these factors in the context of aging remain largely unclear. Here, we formulate a mathematical model for dynamic glucose modulation of a core gene circuit in yeast aging, which not only guided the design of pro-longevity interventions but also revealed the theoretical principles underlying these interventions. We introduce the dynamical systems theory to capture two general means for promoting longevity-the creation of a stable fixed point in the "healthy" state of the cell and the "dynamic stabilization" of the system around this healthy state through environmental oscillations. Guided by the model, we investigate how both of these can be experimentally realized by dynamically modulating environmental glucose levels. The results establish a paradigm for theoretically analyzing the trajectories and perturbations of aging that can be generalized to aging processes in diverse cell types and organisms.

The potential longevity-promoting hypoxic-hypercapnic environment as a measure for radioprotection.

Many biological mechanisms of aging well converge with radiation's biological effects. We used scientific insights from the field of aging to establish a novel hypoxic-hypercapnic environment (HHE) concept for radioprotection. According to this concept, HHE which possesses an anti-aging and longevity-promoting potential, should also act as a radiomitigator and radioprotector. As such, it might contribute greatly to the safety and wellbeing of individuals exposed to high levels of radiation, whether in planned events (e.g. astronauts) or in unplanned events (e.g. first responders in nuclear accidents).

Seed longevity is controlled by metacaspases.

To survive extreme desiccation, seeds enter a period of quiescence that can last millennia. Seed quiescence involves the accumulation of protective storage proteins and lipids through unknown adjustments in protein homeostasis (proteostasis). Here, we show that mutation of all six type-II metacaspase (MCA-II) proteases in Arabidopsis thaliana disturbs proteostasis in seeds. MCA-II mutant seeds fail to restrict the AAA ATPase CELL DIVISION CYCLE 48 (CDC48) at the endoplasmic reticulum to discard misfolded proteins, compromising seed storability. Endoplasmic reticulum (ER) localization of CDC48 relies on the MCA-IIs-dependent cleavage of PUX10 (ubiquitination regulatory X domain-containing 10), the adaptor protein responsible for titrating CDC48 to lipid droplets. PUX10 cleavage enables the shuttling of CDC48 between lipid droplets and the ER, providing an important regulatory mechanism sustaining spatiotemporal proteolysis, lipid droplet dynamics, and protein homeostasis. In turn, the removal of the PUX10 adaptor in MCA-II mutant seeds partially restores proteostasis, CDC48 localization, and lipid droplet dynamics prolonging seed lifespan. Taken together, we uncover a proteolytic module conferring seed longevity.

Role of the central nervous system in cell non-autonomous signaling mechanisms of aging and longevity in mammals.

Multiple organs orchestrate the maintenance of proper physiological function in organisms throughout their lifetimes. Recent studies have uncovered that aging and longevity are regulated by cell non-autonomous signaling mechanisms in several organisms. In the brain, particularly in the hypothalamus, aging and longevity are regulated by such cell non-autonomous signaling mechanisms. Several hypothalamic neurons have been identified as regulators of mammalian longevity, and manipulating them promotes lifespan extension or shortens the lifespan in rodent models. The hypothalamic structure and function are evolutionally highly conserved across species. Thus, elucidation of hypothalamic function during the aging process will shed some light on the mechanisms of aging and longevity and, thereby benefiting to human health.

Advances in clinical application of lipidomics in healthy ageing and healthy longevity medicine.

It is imperative to optimise health and healthspan across the lifespan. The accumulation of reactive oxygen species (ROS) has been implicated in the hallmarks of ageing and inhibiting ROS production can potentially delay ageing whilst increasing healthy longevity. Lipids and lipid mediators (derivatives of lipids) are becoming increasingly recognized as central molecule in tissue and cellular function and are susceptible to peroxidation; hence linked with ageing. Lipid classes implicated in the ageing process include sterols, glycerophospholipids, sphingolipids and the oxidation products of polyunsaturated fatty acids but these are not yet translated into the clinic. Further mechanistic studies are required for the understanding of lipid classes in the ageing process. Lipidomics, the system level characterisation of lipid species with respect to metabolism and function, might provide a significant and useful biological age profiling tool through longitudinal studies. Lipid profiles in different ages among healthy individuals could be harnessed as lipid biomarkers of healthy ageing with potential integration for the development of lipid-based ageing clock (lipid clock). The potential of a lipid clock includes the prediction of future morbidity or mortality, which will promote precision and healthy longevity medicine.

Jurassic fossil juvenile reveals prolonged life history in early mammals.

Living mammal groups exhibit rapid juvenile growth with a cessation of growth in adulthood1. Understanding the emergence of this pattern in the earliest mammaliaforms (mammals and their closest extinct relatives) is hindered by a paucity of fossils representing juvenile individuals. We report exceptionally complete juvenile and adult specimens of the Middle Jurassic docodontan Krusatodon, providing anatomical data and insights into the life history of early diverging mammaliaforms. We used synchrotron X-ray micro-computed tomography imaging of cementum growth increments in the teeth2-4 to provide evidence of pace of life in a Mesozoic mammaliaform. The adult was about 7 years and the juvenile 7 to 24 months of age at death and in the process of replacing its deciduous dentition with its final, adult generation. When analysed against a dataset of life history parameters for extant mammals5, the relative sequence of adult tooth eruption was already established in Krusatodon and in the range observed in extant mammals but this development was prolonged, taking place during a longer period as part of a significantly longer maximum lifespan than extant mammals of comparable adult body mass (156 g or less). Our findings suggest that early diverging mammaliaforms did not experience the same life histories as extant small-bodied mammals and the fundamental shift to faster growth over a shorter lifespan may not have taken place in mammaliaforms until during or after the Middle Jurassic.

The influence of sex-specific factors on biological transformations and health outcomes in aging processes.

The aging process demonstrates notable differences between males and females, which are key factors in disease susceptibility and lifespan. The differences in sex chromosomes are fundamental to the presence of sex bias in organisms. Moreover, sex-specific epigenetic modifications and changes in sex hormone levels impact the development of immunity differently during embryonic development and beyond. Mitochondria, telomeres, homeodynamic space, and intestinal flora are intricately connected to sex differences in aging. These elements can have diverse effects on men and women, resulting in unique biological transformations and health outcomes as they grow older. This review explores how sex interacts with these elements and shapes the aging process.

Polyunsaturated fatty acid status and markers of oxidative stress and inflammation across the lifespan: A cross-sectional study in a cohort with long-lived individuals.

Polyunsaturated fatty acids (PUFA) are known to have a regulatory effect on oxidative and inflammatory processes. This study aimed to identify the relationship between blood PUFA status and circulatory markers of oxidative stress and inflammation in a cohort of 172 subjects. The population was divided by sex and into three age groups: adults (18-64 years old, n = 69), older adults (65-89 years old, n = 54), and long-lived individuals (LLIs, 90-111 years old, n = 49). Whole blood PUFA content was quantified using gas chromatography. Additionally, serum levels of C-reactive protein (CRP), paraoxonase (PON), Trolox equivalent antioxidant capacity (TEAC), and malondialdehyde (MDA) were measured. Our results showed that a higher omega-3 (n-3) index in adult females was a predictor of lower MDA concentrations (p = 0.038). Conversely, total n-3 PUFA and total n-6 PUFA were positively related to MDA values among older adult females and LLI men (p < 0.05), while total n-6 PUFA was inversely correlated with MDA levels in LLI females (p < 0.05). Interestingly, increased concentrations of total n-3 PUFA and n-3 index were positively correlated with higher TEAC values in LLI men (p = 0.007), while the arachidonic acid (AA)/eicosapentaenoic acid (EPA) ratio was inversely correlated with TEAC values among LLI females (p = 0.006). These findings suggest that cellular antioxidant capacity is inversely correlated with changes in the AA/EPA ratio in long-lived females, whereas n-3 PUFA may enhance blood antioxidant capacity in long-lived men. Overall, our study highlights the complex, sex-specific interactions between PUFA profiles and oxidative stress and inflammatory markers across different age groups.

Lifespan differences in hippocampal subregion connectivity patterns during movie watching.

Age-related episodic memory decline is attributed to functional alternations in the hippocampus. Less clear is how aging affects the functional connections of the hippocampus to the rest of the brain during episodic memory processing. We examined fMRI data from the CamCAN dataset, in which a large cohort of participants watched a movie (N = 643; 18-88 years), a proxy for naturalistic episodic memory encoding. We examined connectivity profiles across the lifespan both within the hippocampus (anterior, posterior), and between the hippocampal subregions and cortical networks. Aging was associated with reductions in contralateral (left, right) but not ipsilateral (anterior, posterior) hippocampal subregion connectivity. Aging was primarily associated with increased coupling between the anterior hippocampus and regions affiliated with Control, Dorsal Attention and Default Mode networks, yet decreased coupling between the posterior hippocampus and a selection of these regions. Differences in age-related hippocampal-cortical, but not within-hippocampus circuitry selectively predicted worse memory performance. Our findings comprehensively characterize hippocampal functional topography in relation to cognition in older age, suggesting that shifts in cortico-hippocampal connectivity may be sensitive markers of age-related episodic memory decline.

Probing sustained attention and fatigue across the lifespan.

Trait fatigues reflects tiredness that persists throughout a prolonged period, whereas state fatigue is a short-term reaction to intense or prolonged effort. We investigated the impact of sustained attention (using the SART) on both trait and state fatigue levels in the general population. An online version of the SART was undertaken by 115 participants, stratified across the whole adult lifespan. While pre-task trait fatigue was a strong indicator of the initial state fatigue levels, undergoing the task itself induced an increase in reported subjective state fatigue, and an accompanying reduction in subjective energy rating. Consistent with this finding, greater subjective state fatigue levels were associated with reduced accuracy. In addition, age was the best predictor of inter-participant accuracy (the older the participants, the greater the accuracy), and learning (i.e., task duration reducing reaction times). Moreover, a ceiling effect occurred where participants with higher trait fatigue did not experience greater state fatigue changes relative to those with low trait scores. In summary, we found improved accuracy in older adults, as well as a tight coupling between state fatigue and SART performance decline (in an online environment). The findings warrant further investigation into fatigue as a dynamic, task-dependent state and into SART performance as an objective measure and inducer of fatigue.

Differences in adult nutritional requirements impact the population growth and survival of two related species of rice leaffolders to produce interspecific differentiation.

Nutrition is a limiting feature of species evolution. The differences in nutritional requirements are the evolutionary result of differential adaptations to environmental changes, explaining differences in their ecological traits. Cnaphalocrocis medinalis and Cnaphalocrocis exigua, two related species of rice leaffolders, have similar morphology and feeding properties but different migration and overwintering behaviors. However, it is unclear whether they have evolved adult nutritional differentiation traits to coexist. To explore this issue, this study examined the effects of carbohydrates and amino acids on their reproductive and demographic parameters. The findings indicate that carbohydrate intake prolonged the longevity and population growth of two rice leaffolders, but amino acid intake promoted egg hatching only. However, nutrient deficiency made it impossible for C. medinalis to reproduce successfully and survive, but it did not affect C. exigua. The population expansion and survival of migratory C. medinalis relied on adult nutritional intake. Conversely, the nutrients necessary for C. exigua overwintering activity mostly came from the storage of larvae. The difference in nutritional requirements for population growth and survival between the two rice leaffolders partially explained their differences in migration and overwintering.

What factors preventing the older adults in China from living longer: a machine learning study.

BACKGROUND: The fact that most older people do not live long means that they do not have more time to pursue self-actualization and contribute value to society. Although there are many studies on the longevity of the elderly, the limitations of traditional statistics lack the good ability to study together the important influencing factors and build a simple and effective prediction model. METHODS: Based on the the data of Chinese Longitudinal Healthy Longevity Survey (CLHLS), 2008-2018 cohort and 2014-2018 cohort were selected and 16 features were filtered and integrated. Five machine learning algorithms, Elastic-Net Regression (ENR), Decision Tree (DT), Random Forest (RF), K-Nearest Neighbor (KNN), and eXtreme Gradient Boosting (XGBoost), were used to develop models and assessed by internal validation with CLHLS 2008-2018 cohort and temporal validation with CLHLS 2014-2018 cohort. Besides, the best performing model was explained and according to the variable importance results, simpler models would be developed. RESULTS: The results showed that the model developed by XGBoost algorithm had the best performance with AUC of 0.788 in internal validation and 0.806 in temporal validation. Instrumental activity of daily living (IADL), leisure activity, marital status, sex, activity of daily living (ADL), cognitive function, overall plant-based diet index (PDI) and psychological resilience, 8 features were more important in the model. Finally, with these 8 features simpler models were developed, it was found that the model performance did not decrease in both internal and temporal validation. CONCLUSIONS: The study indicated that the importance of these 8 factors for predicting the death of elderly people in China and built a simple machine learning model with good predictive performance. It can inspire future key research directions to promote longevity of the elderly, as well as in practical life to make the elderly healthy longevity, or timely end-of-life care for the elderly, and can use predictive model to aid decision-making.

Effect of temperature on the biological parameters of pink bollworm, Pectinophora gossypiella Saunders (Lepidoptera: Gelechiidae).

Pink bollworm (PBW) Pectinophora gossypiella is an important pest cotton worldwide. There are multiple factors which determines the occurrence and distribution of P. gossypiella across different cotton growing regions of the world, and one such key factor is 'temperature'. The aim was to analyze the life history traits of PBW across varying temperature conditions. We systematically explored the biological and demographic parameters of P. gossypiella at five distinct temperatures; 20, 25, 30, 35 and 40 ± 1 °C maintaining a photoperiod of LD 16:8 h. The results revealed that the total developmental period of PBW shortens with rising temperatures, and the highest larval survival rates were observed between 30 °C and 35 °C, reaching 86.66% and 80.67%, respectively. Moreover, significant impacts were observed as the pupal weight, percent mating success, and fecundity exhibited higher values at 30 °C and 35 °C. Conversely, percent egg hatching, larval survival, and adult emergence were notably lower at 20 °C and 40 °C, respectively. Adult longevity decreased with rising temperatures, with females outliving males across all treatments. Notably, thermal stress had a persistent effect on the F1 generation, significantly affecting immature stages (egg and larvae), while its impact on reproductive potential was minimal. These findings offer valuable insights for predicting the population dynamics of P. gossypiella at the field level and developing climate-resilient management strategies in cotton.