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Cerebral small vessel disease genomics and its implications across the lifespan
White matter hyperintensities (WMH) are the most common brain-imaging feature of cerebral small vessel disease (SVD), hypertension being the main known risk factor. Here, we identify 27 genome-wide loci for WMH-volume in a cohort of 50,970 older individuals, accounting for modification/confounding by hypertension. Aggregated WMH risk variants were associated with altered white matter integrity (p = 2.5×10-7) in brain images from 1,738 young healthy adults, providing insight into the lifetime impact of SVD genetic risk. Mendelian randomization suggested causal association of increasing WMH-volume with stroke, Alzheimer-type dementia, and of increasing blood pressure (BP) with larger WMH-volume, notably also in persons without clinical hypertension. Transcriptome-wide colocalization analyses showed association of WMH-volume with expression of 39 genes, of which four encode known drug targets. Finally, we provide insight into BP-independent biological pathways underlying SVD and suggest potential for genetic stratification of high-risk individuals and for genetically-informed prioritization of drug targets for prevention trials.
White matter hyperintensities (WMH) are a common brain-imaging feature of cerebral small vessel disease. Here, the authors carry out a GWAS and followup analyses for WMH-volume, implicating several variants with potential for risk stratification and drug targeting.
Journal Article
A research framework for the United Nations Decade of Healthy Ageing (2021–2030)
The mission of UN Decade of Healthy Ageing (2020–2030) is to improve the lives of older people, their families and their communities. In this paper, we create a conceptual framework and research agenda for researchers to knowledge to address the Decade action items. The framework builds on the main components of healthy ageing: Environments (highlighting society and community) across life courses (of work and family) toward wellbeing (of individuals, family members and communities). Knowledge gaps are identified within each area as priority research actions. Within societal environments, interrogating beliefs about ageism and about familism are proposed as a way to illustrate how macro approaches to older people influence their experiences. We need to interrogate the extent to which communities are good places to grow old; and whether they have sufficient resources to be supportive to older residents. Further articulation of trajectories and turning points across the full span of work and of family life courses is proposed to better understand their diversities and the extent to which they lead to adequate financial and social resources in later life. Components of wellbeing are proposed to monitor improvement in the lives of older people, their families and communities. Researcher priorities can be informed by regional and national strategies reflecting Decade actions.
Journal Article
Youth cultures, transitions, and generations : bridging the gap in youth research
\"Within the diversity of contemporary youth research there are two dominant streams that can be categorized under the broad headings of 'transitions' and 'cultures' perspectives. This collection sets forth a challenge to youth studies, with the contributors arguing that social change means it is no longer possible to understand the experience of young people through this transitions/cultures prism. The future of youth studies, it is argued, will require new conceptual foundations, capable of bridging the gap between transitions and cultures approaches to researching youth. The chapters, including contributions from some of the most established names in contemporary youth studies, draw on a wide variety of alternative concepts, including generation, assemblage, field and belonging to rethink how the study of young lives should be pursued in the coming decades. \"-- Provided by publisher.
Book
Integrating Machine Learning with Multi-Omics Technologies in Geroscience: Towards Personalized Medicine
Aging is a fundamental biological process characterized by a progressive decline in physiological functions and an increased susceptibility to diseases. Understanding aging at the molecular level is crucial for developing interventions that could delay or reverse its effects. This review explores the integration of machine learning (ML) with multi-omics technologies—including genomics, transcriptomics, epigenomics, proteomics, and metabolomics—in studying the molecular hallmarks of aging to develop personalized medicine interventions. These hallmarks include genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, disabled macroautophagy, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, altered intercellular communication, chronic inflammation, and dysbiosis. Using ML to analyze big and complex datasets helps uncover detailed molecular interactions and pathways that play a role in aging. The advances of ML can facilitate the discovery of biomarkers and therapeutic targets, offering insights into personalized anti-aging strategies. With these developments, the future points toward a better understanding of the aging process, aiming ultimately to promote healthy aging and extend life expectancy.
Journal Article
Genetic, Socioecological, and Health Research on Extreme Longevity in Semisupercentenarians and Supercentenarians: A Scoping Review
People with extreme longevity represent a unique model to study the biology of aging and discover clues to improve the general population's health. Current scoping reviews systematically map and synthesize the existing literature on supercentenarians and semisuper centenarians to identify key themes, methodologies, and findings that can inform the development of a comprehensive framework for a Global Supercentenarian Cohort Study protocol.
A scoping review was conducted as per PRISMA-ScR guidelines using the PEO framework (population: semisupercentenarians aged 105+; exposure: genetics, socioecological, and other factors; outcome: supercentenarians aged 110+). Seven databases, Scopus, ProQuest, PubMed, PsycINFO, Scopus Secondary literature, Scopus Patents, and Cochrane Database of Systematic Reviews (CDSR), were searched, incorporating data from Scopus Secondary literature. Unpublished data were excluded. The scoping review protocol was published to ensure transparency and rigor.
144 were included. A thematic analysis of individual studies' findings was conducted to identify multidimensional themes of supercentenarian health. The following themes were identified: Age validation theme, demographics theme, behavior theme, personality, traits theme, quality of life theme, well-being and life satisfaction, cognition theme, social theme, religiosity/spirituality theme, independence/self-ability theme, mental health theme, health theme, genetics theme, and ecological theme. There was variability in the methods of assessment and tools used for each theme across different studies and inconsistencies in terminology, with similar concepts such as social support, social engagement, social contact, and social isolation being referred to by different names in various studies.
We propose a comprehensive framework comprising three components: cohort setting, measuring contributing factors, and full assessment. This framework sets the stage for a unified, supranational protocol that harmonizes survey methods across countries, integrates multidisciplinary perspectives, and adopts a longitudinal approach. It would enable larger sample sizes and more robust statistical analyses, allowing researchers to explore complex relationships and derive more accurate conclusions about supercentenarians' health, well-being, and longevity. Developing this unified protocol necessitates the consensus of global experts.
Journal Article
Preparing for the Challenges of Population Aging in Asia
Preparing for the Challenges of Population Aging in Asia discusses the challenges posed by a rapidly aging population and identifies needed research to help policymakers better respond to them. While the percentage of elderly people in nearly every nation is growing, this aging trend is particularly stark in parts of Asia. Projections indicate that the portion of the population age 65 and older will more than triple in China, India, and Indonesia and more than double in Japan between 2000 and 2050, based on data from the United Nations. Moreover, this demographic shift is coinciding with dramatic economic and social changes in Asia, including changing family structures and large-scale migrations from rural to urban areas.
These trends raise critical questions about how nations can develop policies that best support health and economic well-being in large and growing populations at older ages. Governments in Asia still have time to determine the best ways to respond to the unfolding demographic transformation, but taking advantage of this window of opportunity will require new research to shed light on the status and needs of the aging population. Currently the research base on aging in this region is relatively underdeveloped. This book identifies several key topics for research to inform public policy, including changing roles in the family; labor force participation, income, and savings; and health and well-being of the public.
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