Aging & Longevity
The evolution toward integrated community health care for older people in Italy
The progressive aging of the Italian population and the increasing prevalence of multimorbidity and frailty call for a reorganization of health and social care services. In this paper we aim to critically examine Ministerial Decree 77/2022, within Mission 6 of the National Recovery and Resilience Plan, which establishes new models and standards for community-based care and offers an unique opportunity to deliver care that is closer to people's homes, fostering a holistic approach that combines...
Ketogenesis is Dispensable for the Metabolic Adaptations to Caloric Restriction
Caloric restriction (CR) extends the health and lifespan of diverse species. When fed once daily, CR-treated mice rapidly consume their food and endure a prolonged fast between meals. As fasting is associated with a rise in circulating ketone bodies, we investigated the role of ketogenesis in CR using mice with whole-body ablation of Hmgcs2, the rate-limiting enzyme producing the main ketone body β-hydroxybutyrate (βHB). Here, we report that Hmgcs2 is largely dispensable for many metabolic...
Osteosarcopenia, bone-muscle interactions, and frailty risk: A prospective cohort study of community-dwelling older adults
CONCLUSION: In this prospective cohort study, osteosarcopenia increased the risk of frailty. Our interaction analysis suggests therapies targeting bone density and grip strength may mitigate frailty.
A spatially informed matrix normal model for gene co-expression analysis in spatial transcriptomics studies
The rapid advancement of spatially resolved transcriptomics (SRT) technology enables gene expression profiling across tissue locations while preserving spatial context. Gene co-expression analysis in SRT data provides critical insights into how genes function together within the tissue microenvironment. However, existing methods fail to effectively capture the joint influence of gene-gene interactions and spatial dependencies, limiting their biological interpretability. Here, we introduce spMOCA...
Repair of female reproductive function by GDF-9-overexpressing extracellular vesicles via ACVR1B/SMAD2 regulation in ovarian granulosa
Aging in females is characterized by dysfunctional ovaries (DOs). While human umbilical cord mesenchymal stem cell (HucMSC)-derived extracellular vesicles (EVs) have shown promise in ameliorating DO, the mechanisms underlying their effects remain poorly understood. In this study, we investigated the therapeutic potential of growth differentiation factor 9 (GDF-9)-overexpressing EVs (GOEs) on granulosa cells. We identified the activin A receptor type 1B (ACVR1B) as a critical target for the...
miR-375-3p/STX6 Exacerbates Atherosclerosis by Promoting Endothelial Cell Senescence via Activation of TGF-Beta Signals
Atherosclerosis, a key pathological basis of cardio-cerebrovascular diseases, is closely associated with aging and endothelial cell senescence. The role of microRNAs (miRNAs) in regulating endothelial cell senescence and atherosclerosis remains incompletely understood. In this study, we discovered that miR-375-3p expression was significantly elevated in the serum of both aged and atherosclerotic mice. Overexpression of miR-375-3p induced endothelial cell senescence, evidenced by increased...
Preclinical Alzheimer's and vascular biomarkers alter brain aging in cognitively normal adults: a MRI-based study
INTRODUCTION: The aging global population underscores the need to understand brain aging and its links to neurodegenerative diseases. While most brain aging studies use cognitive impairment as exclusion criteria, preclinical biomarkers may influence results, potentially masking early pathological effects. This study evaluates how preclinical AD and vascular biomarkers impact brain aging models in cognitively normal subjects.
Integrated primary care for home-dwelling older adults with mild cognitive impairment in China: a hybrid effectiveness-implementation trial protocol
BACKGROUND: With China’s rapidly aging population, addressing the health management of mild cognitive impairment (MCI) in community settings has become crucial for dementia prevention. This study focuses on developing an integrated primary care intervention (IPC) within primary care system to support home-dwelling older adults with MCI and explore the underlying barriers based on the Consolidated Framework for Implementation Research (CFIR) to the implementation and further scale up of the IPC...
White matter hyperintensity regression: Fact or artifact?
White matter hyperintensities (WMH) are an MRI-based biomarker associated with aging, Alzheimer's disease, and vascular dementia. Although the volume of WMH typically increases over time (growth) for individuals, WMH volume in some cases can also decrease (regress). This suggests the presence of active brain injury recovery mechanisms. Whether WMH regression reflects a true biological phenomenon or results from imaging artifacts or measurement errors, however, remains controversial. Here, we...
Platelet-bioengineered hiPSC-sEVs achieve targeted repair of fibrotic sinoatrial node in preclinical SND models
Sinus node dysfunction, a prevalent arrhythmia in aging populations, is characterized by fibrosis and loss of pacemaker activity, necessitating pacemaker implantation. Current therapies fail to reverse the underlying pathology. Small extracellular vesicles derived from human induced pluripotent stem cells possess regenerative potential but lack targeted delivery. Here, we engineer platelet membrane-fused vesicles that synergistically combine collagen targeting for ischemic injury homing with...
Inhibiting the formation of neutrophil extracellular traps to prevent the recurrence of post-operative glioblastoma
Glioblastoma (GBM) is a highly malignant tumor with a high postoperative recurrence rate. It is crucial to develop innovative and effective approaches to prevent its recurrence. Herein, we focus on the important roles of neutrophil extracellular traps (NETs) in the progression of GBM in mice and patients. Neutrophils accumulate around the surgical cavity and release NETs to promote the proliferation and migration of postoperative residual GBM cells. Injection of a hydrogel loaded with copper...
Predicting the demand of elderly care beds by a novel recursive grey Gompertz model: case studies of Jiangsu and Shanghai, China
CONCLUSIONS: The RGGM model introduces a memory factor into its objective function, which assigns a greater weight to newer observations. This mechanism ensures the priority of new information during the modeling process, enhancing the model's adaptability. Furthermore, the model's structural parameters are solved recursively with each new observation, allowing the parameters to inherit information from previous data points. This recursive approach effectively improves prediction accuracy....
The expectations and influencing factors to choose institutional elder care for older person in the context of future disability: an empirical analysis in China based on Anderson's health behavior model
CONCLUSION: Affected by a variety of factors, the older person's low acceptance of institutional care remains consistent even when future disability is considered. This situation provides the background and ideas for China's current research on promoting social care services. For example, the nursing institutions should consider factors such as the age, education leveland income of the older person when designing elderly care services. The government can lower the threshold for the older person...
Hospitalizations for cardiovascular events and risk for all cause and cardiovascular mortality in elderly patients with atrial fibrillation treated with oral anticoagulants: beyond preventing thromboembolism
CONCLUSIONS: Hospitalizations for CVEs in elderly AF/AFL OAC treated patients increased the risk for all cause and CV mortality within 12 months from admission for AF/AFL. Hospitalization for HF bared the highest risk, but the residual stroke/TIA/SE risk was noteworthy.
IL-27 promotes Treg cell expression of CD122 and fitness at homeostasis
Regulatory T (Treg) cells express high levels of the IL-27R, and in the setting of infection and autoimmunity, the cytokine IL-27 promotes Treg cell activities that mitigate tissue pathology. However, IL-27 appears dispensable for Treg cell development and maintenance as lineage-specific depletion of the IL-27R on Treg cells does not impact these populations at steady state. In contrast, when mice were generated in which the Treg compartment comprised a mix of IL-27R-sufficient and -deficient...
Changing chronomics of clock, immune and Parkinson's disease-associated genes in SCN and SN with aging in male Wistar rats: ketogenic diet intervention
The hypothalamic suprachiasmatic nucleus (SCN) functions as the central circadian pacemaker, synchronizing peripheral clocks through oscillations in core clock genes and proteins. Circadian disruption contributes to immunosenescence, aging, and neurodegenerative disorders such as Parkinson's disease (PD). Previous work from our group demonstrated age-related changes in circadian rhythms of clock genes, protein levels, and serotonin metabolism in the SCN and substantia nigra (SN) of male Wistar...
Atavistic Genetic Expression Dissociation (AGED) During Aging: Meta-Phylostratigraphic Evidence of Cellular and Tissue-Level Phylogenetic Dissociation
Aging is commonly attributed to accumulated damage, or evolved antagonistic genetic trade-offs, which lead to an accumulation of damage causing misexpression of genes necessary for longevity. We propose an atavistic dysregulation of gene expression at cellular and tissue levels during aging, framing aging as a gradual regression toward ancestral cellular states. Similarly to the atavistic model of cancer, in which cells revert to unicellular-like behavior, aging may result from the breakdown of...
Machine learning algorithms to predict frailty in older adults in China: a cross-sectional study
CONCLUSION: ML algorithms can effectively predict the occurrence of frailty in Chinese elderly and identify significant factors associated with frailty. For datasets with complex feature interactions, LightGBM is preferable, while Random Forest offers improved stability and variance control. These findings support ML-based frailty screening and intervention strategies for aging populations.
beta-Hydroxybutyrate Acts as an Exercise Mimetic to Protect the Aging Liver
Liver aging is characterized by pathological features including lipid deposition, exacerbated chronic inflammation, and increased cell death. Although exercise intervention has been proven effective in delaying liver aging, its fundamental biochemical mechanism remains unclear. This study utilized a naturally aged mouse model and an in vitro cellular senescence system to reveal, for the first time, the cascade mechanism by which β-hydroxybutyrate (β-HB), a core protective mediator induced by...
A Novel Longitudinal Proteomic Aging Index Predicts Mortality, Multimorbidity, and Frailty in Older Adults
Previous studies have developed proteomic aging clocks to estimate biological age and predict mortality and age-related diseases. However, these earlier clocks were based on cross-sectional data, capturing only the cumulative aging burden at a single time point but were unable to reflect the dynamic trajectory of biological aging over time. We constructed a longitudinal proteomic aging index (LPAI) using data from 4684 plasma proteins measured by the SomaScan 5K Array across three visits in the...
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