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This commentary highlights the age illusion and advocates integrating biological age and artificial intelligence (AI) to enhance clinical precision in health care. By synthesizing geroscience and machine learning, practitioners and scientists can effectively bridge the gap between experimental biomarkers and personalized medicine and longevity care. This contribution is timely as the importance of biological age and predictive analytics offer transformative potential for diagnostics while...

The condition of having a healthy, functional proteome is known as protein homeostasis, or proteostasis. Maintaining proteostasis is the province of the proteostasis network, which consists of the cellular components that regulate protein synthesis, folding, localization, and degradation. The proteostasis network is a fundamental functional unit in biology with relevance to many diseases. Despite its importance, the human proteostasis network has until now lacked a precise definition, limiting...

Although tau pathology correlates with cognitive decline in Alzheimer's disease (AD), some individuals exhibit resilience by maintaining cognitive function. The mechanisms enabling this protection, particularly before widespread cortical degeneration occurs, remain elusive. Here, we identify a dynamic interplay between cellular vulnerability and circuit-level resilience that shapes cognitive outcomes in AD. Tau accumulation in the Edinger-Westphal nucleus (EW) impairs attention by inducing...

ObjectiveThis study examined the longitudinal effects of social isolation on chronic diseases and depressive symptoms among middle-aged and older adults in South Korea, with attention to gender and age differences.MethodUsing data from three waves of the Korean Longitudinal Study of Aging, longitudinal path analysis was conducted on 5,585 participants.ResultsWomen and older adults showed higher levels of social isolation, chronic diseases, and depressive symptoms, indicating greater...

Speech-in-noise (SIN) perception is a difficult everyday listening task that becomes more difficult with age. Neural tracking of target speech is associated with successful speech perception in clean and noise-degraded listening environments. How aging impacts neural tracking of speech and behavioral decrements in SIN perception remains unclear. To address these questions, we measured neural speech tracking during a continuous SIN perception task in younger and older adults via multichannel...

How cell identity is maintained is a fundamental question, and loss of cell identity is a hallmark of aging associated with multiple age-related diseases. In the adult Drosophila midgut, we identified a posttranscriptional regulatory layer that supervises enterocyte (EC) identity and fails upon aging. Combining single-cell RNA-seq with lineage tracing in aging ECs and classical genetics, we found that aging ECs express genes that unlock the differentiated state. Upon aging, the protein Rogue...

Companion dogs are a valuable geroscience model because they share human environments, develop similar age-related diseases, and have compressed lifespans. The Dog Aging Project (DAP) is a large, prospective cohort designed to investigate intrinsic and extrinsic factors associated with canine aging and longevity. We analyzed 41,047 dogs from the 2024 DAP Curated Data Release with baseline Health and Life Experience Survey (HLES) data and mortality follow-up through 2024. All-cause mortality was...

Neurovascular ageing is a major contributor to cerebrovascular vulnerability and poor stroke outcomes in older adults. Progressive deterioration of the neurovascular unit (NVU), driven by oxidative stress, neurovascular coupling dysfunction, blood-brain barrier (BBB) disruption, inflammageing, cellular senescence, mitochondrial dysfunction, and impaired autophagy compromises neurovascular resilience and increases susceptibility to ischemic injury. Among the molecular pathways implicated in these...

Tumor-associated neutrophil (TAN) enrichment is a defining feature and driving force of brain metastases (BrMs), a leading cause of death in solid tumors. Yet, the mechanisms governing TAN enrichment in BrM remains undefined. Herein, we demonstrate that BrM cell-derived shed soluble mesothelin (sMSLN) critically prolongs neutrophil survival to facilitate tumor cell colonization and outgrowth in the brain. Specifically, sMSLN binds to toll-like receptor 4 (TLR4) on neutrophil to activate the...

Zoonotic viruses originating from mammals pose a persistent threat to global health. While rodents and bats are often considered "special reservoirs," it is debated if spillover risk is driven by specific taxa or merely reflects mammalian species richness. However, most tests have focused on published host-virus association datasets, which can reflect systematic biases in host and virus sampling effort. To address this limitation, we analyzed a comprehensive repository of 4,685 metagenomic...

CONCLUSION: Individuals with cognitive profiles consistent with probable executive MCI were identified using simple assessments of global cognition, memory and executive functions in a community-dwelling older population. As participants were not clinically diagnosed, further prospective studies are needed to determine the screening performance of this approach.

CONCLUSION: Episodic memory practice effects appear to carry meaningful information beyond generic retest-related gains. Explicitly modeling retest effects while preserving interindividual differences in practice-related improvement may refine the characterization of longitudinal cognitive trajectories and help identify subtle early differences in cognitive resilience and vulnerability.

Parkinson's disease involves progressive α-synuclein pathology, but how this reshapes the brain's spatial immunometabolic landscape, and how oligodendrocytes participate, remain incompletely defined. Here we combine single-nucleus RNA sequencing, spatial transcriptomics and spatial metabolomics in male A53T α-synuclein transgenic mice across disease stages, together with male mice carrying adeno-associated virus-mediated α-synuclein overexpression, human midbrain and cerebrospinal fluid samples....

The selective loss of dopaminergic neurons in the substantia nigra pars compacta is a defining feature of Parkinson's disease (PD), yet its underlying mechanisms remain unclear. NUS1, which encodes neurite outgrowth inhibitor-B receptor (NgBR), was recently identified as a PD risk gene. Here we show that NgBR is highly expressed in microglia, where its deficiency drives progressive PD-like motor deficits and dopaminergic neurodegeneration via the LCN2-SLC22A17 iron-transport axis in mice. NgBR...

Despite progress on noble-metal high-entropy alloy catalysts, noble-metal-free high-entropy alloy catalysts continue to face limitations in activity and stability. Atomic defect engineering holds promise for unlocking catalytic potential, yet efficient strategies for designing defects to simultaneously tailor electronic structures and enhance catalytic active sites in noble-metal-free high-entropy alloys remain challenging. Here, we report a general rule to drive twin formation via precisely...

Diet is associated with biological aging, yet few existing dietary indices have been developed specifically to target biological aging. We develop a data-driven, food-based Empirical Dietary Index for Slower Epigenetic Aging (EDISEA) to identify dietary features predictive of lower GrimAge2 acceleration. Higher EDISEA is associated with 4.17 years slower epigenetic aging in the derivation sample of 1,711 participants (P-value < 0.001) and 3.77 years slower aging in an independent sample of 2,311...

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CONCLUSIONS: Serum NfL demonstrated potential as a sensitive and non-invasive biomarker for early detection and staging of cognitive decline. The establishment of population-specific cut-offs within an Indian cohort contributes to global efforts toward standardizing blood-based biomarkers for AD.