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Study reignites debate over what, if anything, machines can feel

Alzheimer's disease is widely conceptualized as a biological continuum initiated by amyloid-β (Aβ) accumulation, followed by tau aggregation and neurodegeneration. Although the ATN framework is commonly used to define disease stages, its static biomarker categories may not fully capture the dynamic pathological transitions that determine the optimal window for anti-Aβ therapies. Here, we introduce a Biological Continuum framework that distinguishes dynamic pathological cascades from static...

Exosomes offer a promising vehicle for noninvasive diagnosis of neurodegenerative diseases by carrying multiple biomarkers across the blood-brain barrier. However, traditional exosome analysis often misses subtle genotype-specific variations because of weak signals from a few exosomes, reliance on markers, and limited understanding of disease signatures. Here, we present a sound way to understand Alzheimer's disease through label-free surface-enhanced Raman scattering (SERS) profiling of...

The ketogenic diet (KD) elevates β-hydroxybutyrate (β-HB), an energy metabolite and signaling molecule with immunomodulatory effects, and has been associated with cognitive and metabolic effects in some preclinical and clinical studies. However, clinical evidence for ketogenic and ketone-based interventions in cognitive aging and Alzheimer's disease remains mixed, and long-term carbohydrate restriction may be difficult to implement in older adults. Dietary supplements that elevate β-HB, such as...

Spontaneous neuronal oscillations support large-scale brain communication and are sensitive to adult aging, yet how their moment-to-moment dynamics change across the adult lifespan and relate to cognition remains unclear. Here, we used resting-state magnetoencephalography (MEG) and time-delay embedded hidden Markov modelling to characterize transient oscillatory brain states in 617 healthy adults aged 18-88 years. Aging was associated with a frequency- and region-specific reorganization of...

Age is a critical determinant of COVID-19 severity, yet the underlying metabolic mechanisms driving disease progression remain poorly understood. Using a well-characterized Syrian hamster model, we investigated how aging shapes intestinal and systemic sterol metabolism during SARS-CoV-2 infection. Young (7-10 weeks) and aged (12 months) hamsters were intranasally infected, and clinical outcomes were integrated with virological, histopathological, and lipidomic profiles across intestinal tissues,...

CONCLUSIONS: Better CVH, as measured by the LE8 score, was associated with fewer and a slower accumulation of age-related health deficits in older adults. These findings suggest that promoting CVH may help delay functional decline and support healthier aging trajectories.

Long-term thermal storage can decarbonize heat utilization by resolving mismatches between heat supply and demand. However, common heat storage materials cannot store energy for long periods. Here, we report an ultralong-term latent heat storage "glass" based on a ternary eutectic sugar alcohol mixture. The as-prepared material exhibits a solid-liquid phase change and glass transition at 423 and 289 K, respectively, with heat release via cold crystallization at 346 K. Remarkably, the glass...

Developing formaldehyde-free and high-performance wood adhesives is imperative for sustainable wood utilization. To overcome performance trade-offs in lignin adhesives, we developed a formaldehyde-free aqueous adhesive formulation via reactive cysteine-functionalized lignin, achieving high performance with an unprecedentedly low lignin loading (20 wt %), which is sprayable and injectable and exhibits excellent fluidity (1.96 mPa·s, 10³ s^(-1)). It undergoes self-curing via forming amide bond,...

Mitochondria play a crucial role in cellular energy metabolism. The heart and brain require a continuous and stable energy supply. Energy production strongly depends on proper mitochondrial function. Mitochondrial fusion and fission, known as "plasticity", are vital for maintaining the normal physiological function of cells. Recent studies have shown that impaired mitochondrial dynamics are present in many aging-related diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), and...

Parkinson's disease (PD) is characterized by the accumulation of Lewy bodies (LBs) in the brain, predominantly consisting of aggregated and phosphorylated α-synuclein (α-Syn). Consequently, strategies to suppress α-Syn expression offer substantial therapeutic potential for PD. This study explores heteroduplex oligonucleotides (HDOs), an innovative gene-silencing technology utilizing DNA/RNA or DNA/DNA hybrids. We designed two HDOs targeting α-Syn: α-Syn-HDO-1 (DNA/RNA) and α-Syn-HDO-2 (DNA/DNA)....

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Neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS), are characterized by pronounced clinical and molecular heterogeneity, as well as highly interconnected pathogenic pathways. This biological complexity has long hindered efforts to systematically define disease mechanisms and to develop effective, targeted therapies. In recent years, clustered regularly interspaced short palindromic repeats (CRISPR) based functional...

Cellular senescence exerts powerful non-cell autonomous effects through the senescence-associated secretory phenotype (SASP). This SASP comprises soluble factors and extracellular vesicles (EVs). Although soluble SASP components can induce senescence in neighboring cells, the specific contribution of EVs to paracrine senescence is poorly defined. Here, we show that EVs released by senescent tumor cells are necessary and sufficient to propagate senescence. Conditioned media from bleomycin-induced...

Thymic involution, the age-related replacement of thymic soft tissue by fat, has been linked to immunosenescence and chronic inflammation, processes implicated in aging-associated comorbidities. Untreated HIV infection is associated with thymic atrophy and reduced thymic output. Although thymic function may normalize after initiation of antiretroviral therapy, the long-term consequences of HIV infection on thymic involution in people with HIV (PWH) remain unknown. We investigated whether thymic...

Mitochondria play a crucial role in cellular energy metabolism. The heart and brain require a continuous and stable energy supply. Energy production strongly depends on proper mitochondrial function. Mitochondrial fusion and fission, known as "plasticity", are vital for maintaining the normal physiological function of cells. Recent studies have shown that impaired mitochondrial dynamics are present in many aging-related diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), and...

Aging is a major risk factor for atherosclerosis and is accompanied by profound changes in the immune system, including effector T cell expansion, senescent cell accumulation, and increased pro-inflammatory signaling. Rapamycin, a promising rejuvenation therapeutic that inhibits mTORC1 and modulates immune aging, was investigated for its potential to attenuate pro-atherogenic immune responses in aged atherosclerotic mice. 80- to 90-week-old male Ldlr^(-/-) mice with established atherosclerotic...

Age-related weakness is strongly associated with disability and mortality in older adults. While muscle atrophy contributes to weakness, strength declines at a faster rate than muscle mass, implicating neural mechanisms such as changes at the spinal cord and neuromuscular junction. Yet, the role of the motor cortex in age-related weakness remains largely unexplored. We previously identified layer V pyramidal neurons (LVPNs) of the primary motor cortex as hyperexcitable in aged mice, but whether...

Mitochondrial quality control is severely impaired in the aging heart, largely attributed to disrupted mitophagy homeostasis. However, the key molecular drivers remain poorly defined, and the translational value of mitochondria-targeted therapy for cardiac aging is still underexplored. Here, we report prominent mitophagy flux congestion in aged cardiac tissue and confirm that mitochondrial transplantation efficiently rescues impaired mitophagy, ultimately rejuvenating the aging heart....

The gut microbiota plays a pivotal role in maintaining intestinal homeostasis and regulating host metabolism, yet its composition and function undergo substantial alterations with aging. However, the relationship between age-associated microbial changes and host intestinal physiology remains not fully elucidated. Here, we employed Bama miniature pigs, a model with close gastrointestinal similarity to humans, to investigate the impact of fecal microbiota transplantation (FMT) from young or...