The Power of a Complex Systems Perspective to Elucidate Aging.

It is becoming highly accepted that aging, age-related diseases, and geriatric healthcare can move forward if reductionist research is complemented by integrative research uniting knowledge on specific aging mechanisms, multiple biomedical, social, psychological, lifestyle, and environmental factors and their interactions. In this special issue, we present exciting papers that illustrate how complexity science theory and practice can be applied to aging research and provide a better understanding and quantification of healthy aging and vulnerability to disease. Recent insights on biomarkers, clocks of aging, frailty, and resilience are covered and studied in interaction with a dynamic multiscale perspective. The editorial and closing viewpoint guide you through basic principles of gerontological complexity science and shed light on new research horizons, including innovative systems-based interventions.

Social isolation and likelihood of becoming centenarians: evidence from the Chinese longitudinal healthy longevity survey.

BACKGROUND: Social isolation, defined as an individual's lack of social connections, is particularly prevalent among older adults. However, its association with health outcomes among the oldest-old population (aged 80 and above) was understudied. AIMS: To examine the association between social isolation and the likelihood of becoming a centenarian among the oldest-old people in China, aiming to provide novel insights into promoting healthy aging and longevity. METHODS: Using data from The Chinese Longitudinal Healthy Longevity Survey, conducted in 22 provinces in mainland China since 1998, we performed a community-based, prospective nested case-control study. The primary outcome was survival to the age of 100 by 2018 (the end of follow-up). Information on social isolation and other covariates was collected via a questionnaire at baseline. The degree of social isolation was categorized as low, moderate, and high. Included (n = 5,716) were 1,584 identified centenarians and 4,132 controls (deceased before reaching 100 years), matched by age, sex, and year of entry. A conditional logistic regression model was used to evaluate the association between social isolation and the likelihood of becoming a centenarian, adjusting for demographic factors, lifestyle factors, chronic disease, potential disability, optimistic attitude, and perceived loneliness. RESULTS: Individuals with the highest social isolation score had lower odds of becoming centenarians (adjusted OR:0.82; 95% CI: 0.68, 0.98), relative to those with the least social isolation (P-value < 0.05), and this association persisted in sensitivity analyses. The association was more pronounced among ever smokers, compared to never smokers (P-value = 0.001). We did not observe significant interactions between social isolation and other covariates (P-value > 0.05 for all). CONCLUSIONS: This study highlights the inverse association between social isolation and the likelihood of becoming a centenarian, emphasizing the need for public health initiatives to combat isolation in the older population.

Application of the Medical Research Council guidance for complex interventions in the development of VIeSA, an intervention to support healthy ageing among community-dwelling older adults.

BACKGROUND: The ageing population, coupled with the desire to age-in-place, highlight the need for programs that target health promotion as a means of maintaining functional ability, autonomy, and independence among community-dwelling older adults. This paper describes the development of the VIeSA intervention, which aimed to model a healthy ageing trajectory, including the identification of the necessary tools and methods, that would allow people older people, in partnership with health and social care professionals, to define personal health-related goals and the actions to achieve them. A key element of the intervention development was the creation of a support tool intended to assist this process. METHODS: The UK Medical Research Council (MRC) guidance on developing and evaluating complex interventions was applied in the development of the intervention and of the support tool. A participatory approach was selected, with stakeholders engaged on different occasions to allow the refinement of the intervention and of the support tool. Following the steps and suggested actions in the MRC development phase, the development process was conducted by identifying (1) the evidence base and (2) the theoretical framework and (3) by modelling the process and outcomes of the intervention. RESULTS: Following a literature review on effective interventions for functional ability, draft 1 of the support tool was designed. Focus groups with stakeholders provided feedback on this draft allowing for its refinement in terms of content, language use, and structure (draft 2). A review of the approaches for health promotion delivery led to further additions to the tool (draft 3) and informed the content of the training of health and social care professionals. After their training, professionals provided feedback on the acceptability, appropriateness, and feasibility of different elements of the intervention. Results suggested that no further major refinement to the intervention or support tool was necessary. CONCLUSIONS: The design and development of the VIeSA intervention using the MRC guidance allowed for a clarity of direction, an optimised content in terms of usefulness and accessibility for all concerned stakeholders, and greater opportunities for its implementation and uptake.

The Influence of Structural Brain Changes on Cognition in the Context of Healthy Aging: Exploring Mediation Effects Through gBAT-The Graphical Brain Association Tool.

The contribution of age-related structural brain changes to the well-established link between aging and cognitive decline is not fully defined. While both age-related regional brain atrophy and cognitive decline have been extensively studied, the specific mediating role of age-related regional brain atrophy on cognitive functions is unclear. This study introduces an open-source software tool with a graphical user interface that streamlines advanced whole-brain mediation analyses, enabling researchers to systematically explore how the brain acts as a mediator in relationships between various behavioral and health outcomes. The tool is showcased by investigating regional brain volume as a mediator to determine the contribution of age-related brain volume loss toward cognition in healthy aging. We analyzed regional brain volumes and cognitive testing data (Montreal Cognitive Assessment [MoCA]) from a cohort of 131 neurologically healthy adult participants (mean age 50 ± 20.8 years, range 20-79, 73% females) drawn from the Aging Brain Cohort Study at the University of South Carolina. Using our open-source tool developed for evaluating brain-behavior associations across the brain and optimized for exploring mediation effects, we conducted a series of mediation analyses using participant age as the predictor variable, total MoCA and MoCA subtest scores as the outcome variables, and regional brain volume as potential mediators. Age-related atrophy within specific anatomical networks was found to mediate the relationship between age and cognition across multiple cognitive domains. Specifically, atrophy in bilateral frontal, parietal, and occipital areas, along with widespread subcortical regions mediated the effect of age on total MoCA scores. Various MoCA subscores were influenced by age through atrophy in distinct brain regions. These involved prefrontal regions, sensorimotor cortex, and parieto-occipital areas for executive function subscores, prefrontal and temporo-occipital regions, along with the caudate nucleus for attention and concentration subscores, frontal and parieto-occipital areas, alongside connecting subcortical areas such as the optic tract for visuospatial subscores and frontoparietal areas for language subscores. Brain-based mediation analysis offers a causal framework for evaluating the mediating role of brain structure on the relationship between age and cognition and provides a more nuanced understanding of cognitive aging than previously possible. By validating the applicability and effectiveness of this approach and making it openly available to the scientific community, we facilitate the exploration of causal mechanisms between variables mediated by the brain.

The validity of studying healthy aging with cognitive tests measuring different constructs.

A clinically useful characterization of the cognitive aging process requires the development of valid and robust behavioral tests, with an emphasis on explaining and understanding typical inter-individual variability in cognition. Here, using a dataset that includes behavioral scores collected with the National Institute of Health Toolbox Cognition Battery (NIHTB-CB) and other auxiliary tests, we examined (1) the differences between young and old adults across different cognitive domains, (2) the strength of across-subject correlations in behavioral test scores, (3) the consistency of low-dimensional behavioral representations across age using factor analysis, and (4) the accuracy of behavioral scores in predicting participants' age. Our results revealed that (1) elderly females had better verbal episodic memory scores than elderly males, (2) across-subject correlations between behavioral tests varied with age group, (3) although a three-factor model explained the behavioral data in both age groups, some tasks loaded to different factors between the two groups, and (4) age-performance relationship (i.e. a regression model linking age to cognitive scores) in one group cannot be extrapolated to predict age in the other group, indicating an inconsistency in age-performance relationships across groups. These findings suggest that executive function tests might tap into different cognitive processes in different age groups, which might ultimately suggest that a statistically significant between-group difference in test performance might not always reflect differences in the same underlying cognitive processes. Overall, this study calls for more caution when interpreting age-related differences and similarities between age groups with different cognitive abilities even when the same tests are used.

Developmental trajectories and heterogeneity of social engagement among Chinese older adults: a growth mixture model.

BACKGROUND: Social engagement is closely related to well-being among older adults. However, studies on the changing trajectory and influencing factors (especially time-varying factors) of social engagement are limited. This study aimed to examine the social engagement trajectory of older Chinese adults and explore its time-fixed and time-varying factors, thus providing evidence for the development of strategies to promote a rational implementation for healthy aging. METHODS: This study included 2,195 participants from a subset of four surveys from the Chinese Longitudinal Healthy Longevity Survey conducted from 2008 to 2018 (with the latest survey completed in 2018), with follow-ups conducted approximately every three years. Growth mixture modeling was used to explore the social engagement trajectory of older adults and the effects of time-varying variables. In addition, multinomial logistic regression was employed to analyze the association between time-fixed variables and latent classes. RESULTS: Three distinct trajectories of social engagement among older adults in China were identified: slow declining (n = 204; 9.3%), which meant social engagement score decreased continuously, but social engagement level improved; slow rising (n = 1,039; 47.3%), marked by an increased score of social engagement, but with an depressed engagement level; and middle stabilizing (n = 952; 43.4%), which meant social engagement score and engagement level remained quite stable. A time-fixed analysis indicated that age, marital status, educational level, and annual family income had a significant impact on social engagement (P < 0.05). In contrast, the time-varying analysis showed that a decline in functional ability, insufficient exercise (means no exercise at present), deteriorating self-reported health and quality of life, negative mood, monotonous diet, and reduced community services were closely related to the reduction in social engagement levels (P < 0.05). CONCLUSION: Three trends were observed at the social engagement level. Older adults with initially high levels of social engagement exhibited a continuous upward trend, whereas those with initially low levels experienced a decline in their social engagement, and those with initially intermediate levels remained quite stable. Considering the primary heterogeneous factors, it is imperative for governments to enhance basic services and prioritize the well-being of older adults. Additionally, families should diligently monitor the emotional well-being of older adults and make appropriate arrangements for meals.

Midlife dynamics of white matter architecture in lexical production.

We aimed to examine the white matter changes associated with lexical production difficulties, beginning in midlife with increased naming latencies. To delay lexical production decline, middle-aged adults may rely on domain-general and language-specific compensatory mechanisms proposed by the LARA model (Lexical Access and Retrieval in Aging). However, the white matter changes supporting these mechanisms remains largely unknown. Using data from the CAMCAN cohort, we employed an unsupervised and data-driven methodology to examine the relationships between diffusion-weighted imaging and lexical production. Our findings indicate that midlife is marked by alterations in brain structure within distributed dorsal, ventral, and anterior cortico-subcortical networks, marking the onset of lexical production decline around ages 53-54. Middle-aged adults may initially adopt a "semantic strategy" to compensate for lexical production challenges, but this strategy seems compromised later (ages 55-60) as semantic control declines. These insights underscore the interplay between domain-general and language-specific processes in the trajectory of lexical production performance in healthy aging and hint at potential biomarkers for language-related neurodegenerative pathologies.

Animal-assisted intervention for geriatric well-being: A comprehensive review.

Background: In recent years, the size of geriatric population seems to have grown larger than that of younger children and is expected to grow even larger in few years from now. As older individuals are more vulnerable to health concerns and loneliness, it is necessary to focus on providing them opportunities for healthy ageing. Animal-assisted therapy (AAT) has emerged as one of the simple yet effective approach to enhance physical, psychological, and social well-being in older adults. Methods: This review article presents collective information from various experiments on AAT's effectiveness in promoting healthy ageing. Results: The physiological impacts of AAT, on cardiovascular health, mobility, and day to day activities have been discussed. The psychological benefits of AAT, such as improvement of mood, cognition, and alleviation of anxiety, loneliness, and depression, are explored. This review also presents the possible mechanisms underlying the effective-ness of AAT, such as release of oxytocin, dopamine, and endorphins, which contribute to emotional well-being along with reduction of stress. The human-animal bond established during AAT sessions is discussed as a significant factor in promoting positive outcomes. Challenges faced and limitations involved in employing therapy animals within ageing populations are also discussed. Conclusions: Avenues for future research and potential applications of AAT in diverse healthcare settings are proposed, emphasizing the need for further empirical investigation to fully elucidate the mechanisms and benefits of AAT for healthy ageing. Through this comprehensive review, we aim to highlight the potential of AAT as a holistic intervention to enhance the well-being of older adults, providing valuable insights for healthcare practitioners, researchers, and policymakers invested in promoting healthy ageing strategies.

Molecular Mechanisms of Healthy Aging: The Role of Caloric Restriction, Intermittent Fasting, Mediterranean Diet, and Ketogenic Diet-A Scoping Review.

As the population ages, promoting healthy aging through targeted interventions becomes increasingly crucial. Growing evidence suggests that dietary interventions can significantly impact this process by modulating fundamental molecular pathways. This review focuses on the potential of targeted dietary strategies in promoting healthy aging and the mechanisms by which specific nutrients and dietary patterns influence key pathways involved in cellular repair, inflammation, and metabolic regulation. Caloric restriction, intermittent fasting, the Mediterranean diet, as well as the ketogenic diet showed promising effects on promoting healthy aging, possibly by modulating mTORC1 AMPK, an insulin signaling pathway. By understanding the intricate interplay between diet and molecular pathways, we can develop personalized dietary strategies that not only prevent age-related diseases, but also promote overall health and well-being throughout the aging process.

Interventions to Promote Physical Activity and Healthy Ageing: An Editorial.

The Healthy Ageing Challenge aims for people to enjoy at least five extra healthy, independent years of life by 2035, while narrowing the gap between the experiences of the richest and poorest [...].

Resting-state EEG correlates of sustained attention in healthy ageing: Cross-sectional findings from the LEISURE study.

While structural and biochemical brain changes are well-documented in ageing, functional neuronal network differences, as indicated by electrophysiological markers, are less clear. Moreover, age-related changes in sustained attention and their associated electrophysiological correlates are still poorly understood. To address this, we analysed cross-sectional baseline electroencephalography (EEG) and cognitive data from the Lifestyle Intervention Study for Dementia Risk Reduction (LEISURE). Participants were 96 healthy older adults, aged 50-84. We examined resting-state EEG periodic (individual alpha frequency [IAF], aperiodic-adjusted individual alpha power [aIAP]) and aperiodic (exponent and offset) activity, and their associations with age and sustained attention. Results showed associations between older age and slower IAF, but not aIAP or global aperiodic exponent and offset. Additionally, hierarchical linear regression revealed that after controlling for demographic variables, faster IAF was associated with better Sustained Attention to Response Task performance, and mediation analysis confirmed IAF as a mediator between age and sustained attention performance. These findings indicate that IAF may be an important marker of ageing, and a slower IAF may signal diminished cognitive processing capacity for sustained attention in older adults.

Structural brain correlates of sustained attention in healthy ageing: Cross-sectional findings from the LEISURE study.

Sustained attention is important for maintaining cognitive function and autonomy during ageing, yet older people often show reductions in this domain. The role of the underlying neurobiology is not yet well understood, with most neuroimaging studies primarily focused on fMRI. Here, we utilise sMRI to investigate the relationships between age, structural brain volumes and sustained attention performance. Eighty-nine healthy older adults (50-84 years, Mage 65.5 (SD=8.4) years, 74 f) underwent MRI brain scanning and completed two sustained attention tasks: a rapid visual information processing (RVP) task and sustained attention to response task (SART). Independent hierarchical linear regressions demonstrated that greater volumes of white matter hyperintensities (WMH) were associated with worse RVP_A' performance, whereas greater grey matter volumes were associated with better RVP_A' performance. Further, greater cerebral white matter volumes were associated with better SART_d' performance. Importantly, mediation analyses revealed that both grey and white matter volumes completely mediated the relationship between ageing and sustained attention. These results explain disparate attentional findings in older adults, highlighting the intervening role of brain structure.

Neurobiological and anti-aging benefits of yoga: A comprehensive review of recent advances in non-pharmacological therapy.

Aging is an unavoidable process marked by numerous physiological and psychological changes that profoundly impact overall health and quality of life. As the global population ages, there is a growing interest in non-pharmacological therapies that can mitigate the adverse effects of aging and promote longevity. This narrative review explores the broad spectrum of non-pharmacological mechanisms offering anti-aging benefits, with a special emphasis on holistic practices such as yoga, meditation, and lifestyle interventions. These therapies influence critical biological processes, including reducing oxidative stress, modulating chronic inflammation, enhancing immune function, and preserving telomere length-key markers of cellular aging. Additionally, these practices contribute to improved cardiovascular health, musculoskeletal strength, and mental well-being, fostering a comprehensive approach to healthy aging. Yoga, for instance, combines physical postures, breath control, and meditation to enhance physical flexibility, mental clarity, and emotional balance. Meditation practices are shown to reduce stress and improve cognitive function, further supporting healthy aging. Lifestyle modifications, such as diet and regular physical activity, complement these therapies by promoting overall vitality and reducing the risk of age-related diseases. This review underscores the potential of integrating these non-pharmacological strategies into daily routines to enhance resilience against aging, improve quality of life, and extend healthspan. Furthermore, it highlights the need for continued research to fully elucidate the mechanisms by which these therapies exert their anti-aging effects and to develop evidence-based guidelines for their implementation.

Discrimination of semantically similar verbal memory traces is affected in healthy aging.

Mnemonic discrimination of highly similar memory traces is affected in healthy aging via changes in hippocampal pattern separation-i.e., the ability of the hippocampus to orthogonalize highly similar neural inputs. The decline of this process leads to a loss of episodic specificity. Because previous studies have almost exclusively tested mnemonic discrimination of visuospatial stimuli (e.g., objects or scenes), less is known about age-related effects on the episodic specificity of semantically similar traces. To address this gap, we designed a task to assess mnemonic discrimination of verbal stimuli as a function of semantic similarity based on word embeddings. Forty young (Mage = 21.7 years) and 40 old adults (Mage = 69.8 years) first incidentally encoded adjective-noun phrases, then performed a surprise recognition test involving exactly repeated and highly similar lure phrases. We found that increasing semantic similarity negatively affected mnemonic discrimination in both age groups, and that compared to young adults, older adults showed worse discrimination at medium levels of semantic similarity. These results indicate that episodic specificity of semantically similar memory traces is affected in aging via less efficient mnemonic operations and strengthen the notion that mnemonic discrimination is a modality-independent process supporting memory specificity across representational domains.

Geroscience in the continuum from healthy longevity to frailty.

The socioeconomic and technological developments of the past decades have enabled unique progress associated to increased life expectancy and better health for a large part of the world's population; however, multimorbidity, frailty and disability are also on the rise. Geroscience as the new biology of aging is based on the evidence that the main risk factor for noncommunicable chronic diseases (NCD) is the aging process; however, its technology is mostly used for the scientific study of longevity and its interaction with aging medicine and geriatrics is still limited. In this perspective, the need for a tighter exchange between geroscience and geriatrics for longer health span and intrinsic capacity is discussed in the context of existing evidence and knowledge gaps.

Understanding healthy ageing in India: insights from multivariate regression trees.

BACKGROUND: Population ageing represents a significant global challenge, particularly pronounced in countries like India. AIMS: This study aims to explore how factors such as socio-economic status, behaviour, and health influence healthy ageing across the Indian older population. METHODS: In this study, we utilized the Longitudinal Ageing Study in India - wave 1 dataset for analysis purposes. Scores were generated for five dimensions of healthy aging, including physical, functional, mental, cognitive, and social aspects and these scores were treated as the target variables. Multivariate Regression Trees analysis was employed to identify the behavioural and socio-demographic factors associated with each dimension of healthy ageing. RESULTS: Years of education emerge as crucial across all dimensions, positively impacting cognitive health and mitigating age-related decline in healthy ageing. Marital status, engagement in household activities, spiritual practices, and living arrangements impacts the scores of different aspects of healthy ageing. Gender disparities in healthy aging are noticeable in the 60-74 age group, with women generally having lower scores. Safety of the living environment is a crucial determinant of the mental health of the elderly across all age groups.These findings highlight the complex interplay of factors in healthy ageing outcomes. CONCLUSION: Our study emphasizes the pivotal role of education in fostering healthy ageing in India. Factors such as environmental safety and social participation also influence well-being. Targeted interventions addressing education, gender equality, safety, and healthcare access are vital for enhancing the ageing experience and overall well-being of older adults.