Aging & Longevity
Mineralogical controls of the oceanic nickel cycle
Transition metals and their isotopes are promising paleo-productivity proxies, but their utility depends on understanding their cycling between sediment and seawater. Using nickel (Ni) as an example, we show how manganese (Mn) minerals control its isotopic composition in oxic marine sediments. By analysing synthetic and natural samples, and simulating sediment diagenesis, we find that most Ni isotope variability in modern Mn-rich sediments is driven by the relative contribution of two bonding...
Quantitative assessment of asymptomatic spinal cord compression using MRI: a multi-center study
Aging is associated with an increased risk of neurodegenerative conditions, including degenerative cervical myelopathy (DCM), a leading cause of neurological disability in older adults. Asymptomatic spinal cord compression (ASCC) represents a potential precursor to DCM, characterized by spinal cord compression in individuals without overt clinical symptoms. Early identification and quantification of ASCC are critical for preventing age-related neurological decline. However, a standardized...
Frailty phenotype state transitions among older adults with a history of cancer and diabetes
CONCLUSIONS: Diabetes and cancer were both associated with an increased frailty prevalence; however, only older adults with diabetes or cooccurring diabetes and cancer had an increased 9-year incidence of frailty relative to older adults without a history of either condition. Future research should explore the underlying mechanisms driving frailty state transitions among chronic disease populations and evaluate targeted interventions to mitigate frailty progression.
Fostering active aging in older adults: results of a communication and social skills program
CONCLUSION: This study contributes valuable evidence supporting psychosocial interventions for active aging. To advance this field, further research should focus on the long-term impact, cultural adaptability, and multimodal strategies that comprehensively address physical, cognitive, and social domains.
T-CLASS: An Online Tool for the Identification and Classification of Aging and Senescence Using Transcriptome Data
Transcriptome analysis has become increasingly utilized in aging research. However, the identification of the key molecular changes underlying aging processes and longevity-promoting regimens from transcriptome data remains challenging. Here, we present Transcriptomic CLassification via Adaptive learning of Signature States (T-CLASS), an online tool that identifies, from transcriptome data, gene sets of several hundred genes that provide an optimal representation of longevity and aging...
Drivers of the pre-season drought thresholds triggering earlier autumn foliar senescence in the Northern Hemisphere
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...
Handgrip strength, dynapenia, and health-related quality of life in older Korean adults
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.
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
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...
Restoring resident tissue macrophages to combat aging and cancer
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...
Aging reshapes the adaptive immune system from healer to saboteur
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...
Sustained immune youth risks autoimmune disease in the aging host
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...
Immune surveillance of senescent cells in aging and disease
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...
Metabolic regulation of immunological aging
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...
Understanding and improving vaccine efficacy in older adults
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...
Toward precision interventions and metrics of inflammaging
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...
Mitochondrial bioenergetics in resilience of older adults with gynecologic cancer: design and rationale of a pilot study
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...
Stress granule-mediated ZBP1 activation drives necroptotic cell death in non-obstructive azoospermia and testicular aging
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...
HAPLN2 forms aggregates and promotes microglial inflammation during brain aging in mice
Protein aggregation is a hallmark of neurodegenerative diseases and is also observed in the brains of elderly individuals without such conditions, suggesting that aging drives the accumulation of protein aggregates. However, the comprehensive understanding of age-dependent protein aggregates involved in brain aging remains unclear. Here, we investigated proteins that become sarkosyl-insoluble with age and identified hyaluronan and proteoglycan link protein 2 (HAPLN2), a hyaluronic acid-binding...
From Clock to Clock: Therapeutic Target Discovery for Aging and Age-Related Diseases
The aging population worldwide necessitates the development of novel therapeutics that enhance the quality of life by preventing and treating age-related diseases. In this review, we first discuss the advantages of a dual-purpose target identification strategy for aging and age-related diseases, with assessment of the hallmark of aging as an approach to identify such dual-purpose targets. Resulting from a convergence of aging research with machine learning (ML) and other artificial intelligence...
Interplay between depressive symptoms and Alzheimer's disease dementia: unraveling the potential roles of ADAM10 and Negr1
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...
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