Aging & Longevity

Emerging evidence highlights the crucial role of peripheral immune cells in maintaining brain homeostasis and their influence on the pathology of Alzheimer disease (AD). Genome-wide association studies have identified numerous AD risk variants in genes expressed by immune cells, implicating innate and adaptive immune pathways in disease progression. Advances in neuroimmunology have revealed that immune cell crosstalk involving T cells, B cells, monocytes and/or macrophages and neutrophils can...

BACKGROUND: The increasing demands of an aging population, healthcare workforce shortages, financial constraints, and a shift in care perspectives call for rethinking geriatric rehabilitation (GR). To ensure GR remains sustainable, a transition towards home-based GR is proposed, reducing the need for prolonged inpatient GR. This study assesses the outcomes, costs and feasibility of the "Better@Home" program, in which home-based GR replaces part of inpatient GR.

CONCLUSION: The high prevalence of chronic pain and pain underestimation in older adults underscores the necessity for comprehensive pain management strategies adopting a patient-centered medicine approach. The provision of education to both physicians and patients on appropriate chronic pain management strategies and options may benefit older adults with chronic diseases.

Aging is associated with a progressive decline in physiological resilience, often linked to impaired stress responses and metabolic dysfunction. In Caenorhabditis elegans (C. elegans), caloric restriction (CR) and pharmacological interventions are widely used to dissect conserved longevity pathways. Here, we identify the N-methyl-D-aspartate receptor (NMDAR) antagonist memantine as a novel modulator of lifespan and stress tolerance in C. elegans. Memantine, but not ketamine, extends median...

Accumulating evidence indicates that Alzheimer disease (AD) is caused by dysregulated microglial phagocytosis. The main risk factor for AD is age, and ageing reduces microglial phagocytosis of amyloid-β (Aβ) plaques, while increasing microglial phagocytosis of synapses and neurons. Most of the known genetic risk for AD can be linked to microglial phagocytosis, including ABCA1, ABI3, ACE, ADAM17, APOE, APP, BIN1, BLNK, CD2AP, CD33, CLU, CR1, CTSB, CTSH, EED, GRN, INPP5D, LILRB2, PICALM, PLCG2,...

Frontotemporal dementia (FTD) is driven by progranulin haploinsufficiency, in which age-dependent microglial activation promotes neurodegeneration through TDP-43 proteinopathy. Cyclic phosphatidic acid (cPA) is a natural phospholipid mediator characterized by a unique cyclic phosphate ring at the sn-2 and sn-3 positions of its glycerol backbone. A pharmacologically active derivative of cPA has been shown to suppress microglial activation. Based on this, we aimed to investigate the potential of...

Vascular aging is a key driver of cardiovascular disease, yet models capturing its complexity in humans are lacking. Hutchinson-Gilford progeria syndrome (HGPS), a premature aging disorder caused by the LMNA mutation, provides a model to study accelerated vascular decline. Here, we developed a blood vessel organoid (BVO) model from HGPS-mutant human embryonic stem cells (hESCs). These BVOs model HGPS vascular defects and reveal significant downregulation of serum response factor (SRF), a trend...

Postural balance in older adults is a key research focus, as impaired balance significantly increases fall risk, potentially leading to severe injury or mortality. Given age-related sensory decline, force-platform posturography assessing sensory perturbation effects could elucidate postural control deficits in aging. This systematic review and meta-analysis examines older adults' ability to maintain quiet stance during sensory perturbations. We searched 8 databases for studies evaluating older...

Photoaging is a process of accelerated skin aging induced by ultraviolet radiation (UVR) and other exogenous factors, characterized by deepened wrinkles, collagen degradation, and inflammatory responses. With increasing public interest in maintaining healthy skin and delaying aging, natural proteins and their bioactive peptides have emerged as promising candidates in anti-photoaging research due to their potent antioxidant, anti-inflammatory, and extracellular matrix (ECM) metabolism-regulating...

Aging is the primary risk factor for cardiovascular disease, cancer, neurodegeneration, and other chronic disorders. Therefore, targeting the hallmarks of aging has emerged as a promising strategy to extend healthspan. Liver X receptors (LXRs) are ligand-dependent nuclear receptors that are activated by specific oxysterols and cholesterol derivatives. They are traditionally known as key regulators of cholesterol homeostasis. However, recent evidence reveals that LXRs also influence autophagy,...

Amyloid-β (Aβ) plaques are one of the primary biomarkers of Alzheimer's Disease (AD). Other publications have reported various mechanisms regarding the clearance of Aβ, and recent studies have also investigated the relationship between daily rhythms of Aβ and AD. The intent of this study was to determine if the circadian rhythm of Aβ differed between a region that was more vulnerable to AD-related pathology (the olfactory bulbs; OB) compared to a region that is less vulnerable (the cerebellum;...

Multiple myeloma (MM) remains an incurable disease despite therapeutic advancements extending survival. Relapses driven by drug resistance and minimal residual disease underscore the need for novel treatment strategies. Natural Killer (NK) cells play a key role in MM immunity, yet their function is suppressed by inhibitory cytokines and metabolites from the tumor microenvironment. Developing anticancer drugs with immunomodulatory properties, such as enhancing tumor sensitivity to NK cell...

Endometrial cancer (EC) is one of the most common gynecologic malignancies amongst women worldwide. Its incidence and mortality rates have been increasing in the last decade. In the present work, we built a patient EC-derived organoid (PDOs) platform that faithfully recapitulated tumor phenotype, genomic alterations, and expression profiles of matched-primary cancer tissues. Interestingly, we found that the response of EC-derived PDOs to both standard therapy and a wide range of targeted drugs...

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CONCLUSIONS: Given the complexity and significant unmet needs among older adults, AI's potential benefits and harms are both heightened in this population. Appropriate guardrails are needed to leverage the benefits of AI while mitigating potential harms. Our findings have implications for technology developers to design innovations that align with the stakeholders' perceived roles for AI, for regulatory bodies to incorporate stakeholders' concerns when developing AI regulations, and for health...

Autophagy preserves neuronal integrity by clearing damaged proteins and organelles, but its efficiency declines with aging and neurodegeneration. Depletion of the oxidized form of nicotinamide adenine dinucleotide (NAD^(+)) is a hallmark of this decline, yet how metabolic restoration enhances autophagic control has remained obscure. Meanwhile, alternative RNA splicing errors accumulate in aging brains, compromising proteostasis. Here, we identify a metabolic - transcriptional mechanism linking...

CONCLUSION: Frailty serves as a critical mediator between disability, anxiety and depression in older adults with chronic disease comorbidity. Targeted interventions addressing disability and frailty may significantly mitigate anxiety and depression, thereby improving mental health and quality of life in this vulnerable population.

CONCLUSION: This study suggests that clear guidance regarding postoperative rehabilitation exercises and multidisciplinary management protocols including individualized exercise plans, collaborative multidisciplinary rehabilitation strategies, and the development of smart devices may be important for healthcare providers in supporting patients' rehabilitation management. Based on participants' experiences, these approaches show potential for contributing to the alleviation of postoperative...

CONCLUSIONS: This study developed interpretable, gender-specific machine learning models for CVD risk prediction in the oldest old population using routine biomarkers. The models demonstrated good discrimination and calibration, offering a practical tool for identifying high-risk individuals who may benefit from targeted preventive interventions. These findings suggest the potential utility of biomarker-based machine learning approaches in cardiovascular risk assessment for the rapidly growing...

There is a growing contradiction between the rising demand for mechanical ventilation among the elderly and their heightened sensitivity to ventilator-induced lung injury (VILI). This discrepancy compels us to explore therapeutic targets for VILI in elderly patients. Our research revealed that aging increases the sensitivity of pulmonary endothelial cells to low-magnitude mechanical stretch. By analyzing transcriptome sequencing data from lung tissues of humans and mice at different ages, as...