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CONCLUSION: In conclusion, this study provides evidence that Apremilast may exert protective effects against Aβ-induced cytotoxicity in BV2 and HT-22 cells by modulating the PI3K/Akt signaling pathway. However, further validation of its dosage and efficacy in vivo is required.

α-Synuclein (α-syn) fibrils accumulate in Parkinson's disease, spreading between cells to template misfolding and drive neurodegeneration. α-Syn fibril entry into healthy neurons is a key step. Here, we comprehensively assessed the membrane proteome for α-syn fibril binding. We identified mGluR4 and NPDC1 as nigral surface proteins binding and internalizing α-syn fibrils. While striatal α-syn fibril injection led to nigral dopamine neuron loss in wild type mice, deletion of either Grm4 or Npdc1...

Alzheimer's disease (AD) is a major public health concern in societies with increasingly ageing populations. Accumulating evidence implies a specific link between the development of tauopathy, cognitive impairment, and sleep loss in AD patients. P301S mutant tau-transgenic (PS19) mice, modelling frontotemporal dementia (FTD) and AD tauopathy, demonstrate sleep loss and cognitive impairment. We aimed to assess the progression of sleep loss and cognitive decline longitudinally in both sexes of...

Neuromuscular transmission plays a crucial role in muscle function, with differences in neurotransmitter release potentially influenced by sex and aging. While hormonal effects on neurotransmission have been studied, their impact on acetylcholine (ACh) release at the neuromuscular junction remains largely unexplored. Understanding these differences could provide insights into age-related muscle function decline and sex-specific variations in neuromuscular disorders. This study aims to...

Myeloid-derived suppressor cells (MDSCs) are recognized as a key mediator of immunosuppression in aging, which induce immunosenescence and increase elderly people's susceptibility to infections, cancers, autoimmune diseases, and degenerative diseases. However, the commonly used MDSC markers overlap with those defining healthy and normal neutrophils or monocytes, which makes it challenging to distinguish MDSCs from their myeloid counterparts, and hampers deeper understanding of the...

CONCLUSION: This study demonstrates that Rb1 attenuates DNA damage, thus ameliorating structural remodeling and biomechanical function of the aging aorta, and delaying vascular aging and apoptosis. Our findings suggest that Rb1 counteracts age-related aortic impairment, potentially by targeting the DNA damage pathway, which highlights its therapeutic potential against vascular aging.

CONCLUSION: The findings suggest that adapted tango may be an effective non-pharmacological intervention for enhancing executive and cognitive functions in older adults, with potential implications for promoting cognitive health in aging populations.

Social determinants of health (SDHs) are the primary drivers of health inequalities, but whether biological aging plays a role in linking SDHs to health outcomes remains unclear. Here we utilize detailed information on social determinants across five domains, clinical parameters and electronic health records from the UK Biobank and US NHANES to examine the associations between combined SDHs, accelerated biological aging, and health outcomes. Compared with participants in the favourable SDH...

Lung aging is a multifactorial series of molecular alterations that leads to gradual deterioration of lung function and increased vulnerability to cancer. Tumor communicates with host organs partially through extracellular vesicles; however, the mechanistic drivers and consequences of lung aging in the context of cancer remain unclear. Here we identify cancer cell-secreted dimethylarginine dimethylaminohydrolase-1 (DDAH1) protein induces citrulline accumulation and promotes lung fibrosis and...

CONCLUSION: An 8-week lifestyle counseling intervention significantly improved intrinsic capacity and its domains in older women. These findings support the implementation of targeted, multidomain interventions to promote healthy aging, though longer-term studies are needed to assess sustained benefits.

Sepsis-associated secondary infection often leads to a high mortality rate. Dysfunctional macrophages are primary contributors to inadequate antimicrobial defense in patients with sepsis-associated immunosuppression. Rejuvenating macrophage antibacterial capacity is beneficial for host defense against secondary infection. Here, we developed "BATMAN" (bacteria-targeted transformable macrophage nanorejuvenator), a self-assembling peptide nanoparticle to tackle sepsis-associated secondary infection...

The right vagus nerve is essential for cardiac homeostasis, and its intrathoracic resection can lead to postoperative cardiac complications. Strategies to restore vagal innervation after transection at the cardiac level remain lacking. Here, we show that early reconnection of the right vagus nerve using an implantable chitosan/poly-ε-caprolactone cuff-like nerve guidance conduit preserved cardiac mechanical function in adult male minipigs subjected to right cardiac vagotomy. Treated animals...

Urolithin A is an anti-aging and anti-inflammatory gut bacterial metabolite derived from ellagic acid (EA), a polyphenol abundant in berries and nuts. The conversion of EA to urolithin A involves multiple chemically challenging phenol dehydroxylation steps that produce urolithins with varying bioactivities. Despite their biological and chemical significance, the bacterial enzymes responsible for urolithin production remain largely unidentified. Here, we use differential gene expression analysis,...

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent condition increasingly recognized in aging populations. However, its clinical relevance in older adults-particularly in relation to sarcopenia, cognitive function, and rehabilitation outcomes-remains poorly defined. This retrospective observational study included in-patients admitted for geriatric rehabilitation in 2022 with available abdominal ultrasound. MASLD was defined according to AASLD/EASL criteria....

Facial wrinkling is a prominent sign of aging, yet individuals exhibit unique trajectories of biological aging, contributing to the variability in facial appearance. Here, we present a pioneering study exploring the association between lifestyle choices, DNA methylation, and SNP genotypes with a range of facial skin aging phenotypes. The study demonstrated that age-related facial skin phenotypes are influenced by multiple environmental stressors. Epigenome-wide association analyses identified...

BACKGROUND AND OBJECTIVES: Ageing populations present new challenges for society, governments and for health systems. To accommodate the global demographic shift towards older populations, healthcare systems preparedness is of paramount importance. To prepare and equip health systems to best support older adults' health and well-being over the long-term it is necessary to understand how current systems may unintentionally marginalize older adults. Therefore, the purpose of this review and...

Autophagy is a major intracellular degradative process required for maintaining homeostasis in multicellular organisms. Aberrant autophagy is considered to induce internal environmental disturbance and cell death. Therefore, it is of great significance to explore the regulatory mechanism of autophagy. Here, we report a positive role of protein Pira, a SUMO protease, in inducing autophagy and autophagy-dependent cell death during Drosophila development. We found that overexpression of pira in...

CONCLUSION: This study elucidates the underlying mechanisms between neighborhood environment and physical activity among older adults, Neighborhood environment is not only directly associated with physical activity levels among older adults but also indirectly influences physical activity through two psychological cognitive mediators: self-efficacy and outcome expectations.

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