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Biobank-scale genetic characterization of Alzheimer's disease and related dementias across diverse ancestries

5 months 4 weeks ago
Alzheimer's disease and related dementias (AD/ADRDs) pose a significant global public health challenge. To effectively implement personalized therapeutic interventions on a global scale, it is essential to identify disease-causing, risk, and resilience factors across diverse ancestral backgrounds. This study leveraged biobank-scale data to conduct a large multi-ancestry whole-genome sequencing characterization of AD/ADRDs. We thoroughly explored the role of protein-coding and splicing variants...
Marzieh Khani

Astrocyte priming enhances microglial Aβ clearance and is compromised by APOE4

5 months 4 weeks ago
The innate immune system can develop a form of memory called priming, where prior exposure to a stimulus enhances subsequent responses. While well-characterized in peripheral immunity, its function in brain-resident cells such as astrocytes under non-disease conditions remains unclear. Here we show that human astrocytes derived from the induced pluripotent stem cells of healthy female donors, but not microglia, acquire a primed state following transient immune stimulations. Upon subsequent...
Se-In Lee

Drivers of the pre-season drought thresholds triggering earlier autumn foliar senescence in the Northern Hemisphere

5 months 4 weeks ago
Global warming can postpone the autumn date of foliar senescence (DFS). Nevertheless, warming-associated droughts may induce earlier DFS. However, pre-season drought thresholds triggering an earlier DFS (PDT-DFS) are not clearly established. Using site-level DFS data since 1951, satellite-derived DFS data for 1982‒2021, and drought indices, we construct a copula-based Bayesian framework to identify the PDT-DFS over the Northern Hemisphere (>30°N). A higher probability of droughts is associated...
Wenbo Yan

Handgrip strength, dynapenia, and health-related quality of life in older Korean adults

5 months 4 weeks ago
CONCLUSIONS: Reduced HGS and the presence of dynapenia were significantly associated with lower HRQoL, particularly among women. These findings highlight the critical role of muscle strength in maintaining the well-being of aging populations. Further longitudinal studies are warranted to validate these associations and elucidate potential causal mechanisms.
Keunjoong Yoo

Elements of burden among informal caregivers of community-dwelling older adults receiving home care nursing: a cross-sectional study on health status, well-being, and gender differences

5 months 4 weeks ago
CONCLUSIONS: Caregiver burden is a multidimensional construct with significant implications for caregiver well-being. Key predictors of reduced well-being include self-perceived burden, multifaceted strain, and a diminished sense of life satisfaction. Gender differences were notable, with women reporting higher levels of strain and role overload. These findings underscore the need for comprehensive and gender-sensitive support strategies. Addressing social, financial, physical, and psychological...
Sirry Sif Sigurlaugardottir

Restoring resident tissue macrophages to combat aging and cancer

5 months 4 weeks ago
Perturbations to the immune system influence organismal aging, yet identifying effective therapeutic targets that mitigate aging-related tissue decline or the pathogenesis of aging-related diseases, such as cancer, remains challenging. In this Perspective, we focus on the dysfunction and loss of resident tissue macrophages (RTMs) with aging of certain tissues, which promote local inflammation, compromise tissue health and contribute to tumorigenesis. The abnormal genesis of RTMs from the bone...
Matthew D Park

Aging reshapes the adaptive immune system from healer to saboteur

5 months 4 weeks ago
The classical role of adaptive immunity as a protector against external threats has expanded to include its functions in cancer surveillance, tissue repair and regeneration, and, more recently, it has emerged as a regulator of the aging process. In this Perspective, we discuss the mechanisms by which the deterioration of adaptive immunity contributes to inflammaging, cellular senescence and age-associated pathologies. We propose that age-related changes in lymphocytes contribute to aging through...
Sandra Delgado-Pulido

Sustained immune youth risks autoimmune disease in the aging host

5 months 4 weeks ago
Immune responses underlying autoimmune diseases follow the same principles that protect individuals from infection and malignancies. However, while protective immunity wanes with progressive age, the risk for autoimmune disease steadily increases; incidence rates for many autoimmune diseases peak in later life. Here, we discuss whether aging predisposes to autoimmunity, arguing that disease progression in the autoimmune vasculitis giant cell arteritis is driven by age-inappropriate sustenance of...
Cornelia M Weyand

Immune surveillance of senescent cells in aging and disease

5 months 4 weeks ago
Senescent cells are intrinsically immunogenic and can be eliminated by the immune system to facilitate tissue repair and regeneration. However, immune-mediated elimination is compromised with age, causing senescent cell accumulation in tissues, thus limiting healthspan and lifespan and promoting age-related diseases such as cancer. Here, we review how different components of the innate and adaptive immune systems, including natural killer cells, macrophages, neutrophils, dendritic cells, T cells...
Julia Majewska

Metabolic regulation of immunological aging

5 months 4 weeks ago
All biological activities require energy through the intake and generation of metabolites. After reproductive age, altered metabolism, together with cellular and molecular perturbations in the immune system, are linked to organismal functional decline. Unresolved chronic inflammation originating from innate immune cells and loss of naive T cells with restriction of T cell receptor repertoire diversity emanating from age-related thymic involution are some of the mechanisms that limit healthspan...
Hee-Hoon Kim

Understanding and improving vaccine efficacy in older adults

5 months 4 weeks ago
Cellular aging of the immune system, commonly referred to as 'immunosenescence', drives a substantial decline in vaccine efficacy among older adults, who are already typically at a higher risk of reduced infection control. Therefore, preventive medicine requires novel strategies to improve vaccination in older adults, particularly by finding ways to mitigate immunosenescence and chronic inflammation. Here, we review how technical innovations, such as increased antigen amounts, improved adjuvants...
Sebastian J Hofer

Toward precision interventions and metrics of inflammaging

5 months 4 weeks ago
Inflammaging describes a chronic, systemic, low-grade inflammatory state that is recognized as a major risk factor for age-related diseases (ARDs) and a pivotal convergence point of multiple biological mechanisms involved in aging. Here, we discuss the heterogeneity of inflammaging, proposing that it emerges as a consequence of each individual's lifelong exposures to inflammatory stimuli, shaped by a unique combination of genetics, lifestyle, socioeconomic conditions and environmental factors...
Claudio Franceschi

Interplay between depressive symptoms and Alzheimer's disease dementia: unraveling the potential roles of ADAM10 and Negr1

5 months 4 weeks ago
Late-onset depression (LOD) is closely linked to Alzheimer's disease (AD), marked by shared biological pathways and common risk factors. The neurobiological alterations associated with depression, particularly the dysregulation of amyloid-β (Aβ), play a critical role in the acceleration of disease progression. In individuals suffering from LOD, Aβ peptides - specifically Aβ40 and Aβ42 - exhibit distinct profiles in plasma, cerebrospinal fluid (CSF), and brain tissue, highlighting the substantial...
Danilo Barroso de Sousa

Mitochondrial bioenergetics in resilience of older adults with gynecologic cancer: design and rationale of a pilot study

5 months 4 weeks ago
Resilience-the ability to recover and maintain function following stresses-is a critical factor influencing treatment tolerance and recovery in older adults with cancer. Despite the high incidence of gynecologic cancers in postmenopausal individuals, resilience in this population remains underexplored, even though patients commonly face compounded stress from both chemotherapy and surgery. The goal of our research is (1) to test the feasibility of cognitive and physical function assessments in...
Anna Kuan-Celarier

Stress granule-mediated ZBP1 activation drives necroptotic cell death in non-obstructive azoospermia and testicular aging

5 months 4 weeks ago
Male infertility remains a major unmet medical challenge, with poorly defined molecular mechanisms and no effective therapies. Here, we identify a stress granule-mediated necroptotic pathway as a key driver of non-obstructive azoospermia, a severe form of male infertility marked by the loss of spermatogenesis. Environmental or physiological stress activates eIF2α kinases, inducing stress granule formation and the recruitment of ZBP1 and RIPK3 into a cytoplasmic complex. This assembly triggers...
Hongen Lei