Aggregator

No abstract

The potential of proteomic aging clocks for obesity research, and the extent of nonlinearity in longitudinal associations between body weight and biological aging, remain underexplored. We investigated how BMI at ages 18 and ~60, as well as changes in BMI from age 18 to ~60, relate to downstream epigenetic and proteomic aging. We also examined nonlinearity and interactions in these associations. Analyses were conducted in 401 Finnish twins with up to nine self-reported or measured BMI values...

CONCLUSION: These findings place mitochondrial proteome collapse at the center of aging and AD-seeded pathology, distinguish Aβ- and Tau-driven proteotoxic routes, and nominate a conserved panel of aggregation-prone proteins as mechanistic drivers and candidate biomarkers for early detection and intervention in AD.

Long-overlooked Kepler signal discovered by citizen scientists reveals promising world worth a closer look

Blood-brain barrier (BBB) dysfunction is a hallmark of many diseases of the brain, including those that represent the largest healthcare burden (for example, Alzheimer disease and stroke). Despite this, rejuvenation and repair of the BBB is not a mainstream concept. During life, the BBB is subjected to perturbations and stresses from a wide range of endogenous or exogenous sources, which can promote brain health or can lead to brain pathologies. The BBB supports many functions that are critical...

Emerging evidence suggests that Parkinson's disease (PD) may have its origin in the enteric nervous system (ENS), from where α-synuclein (αS) pathology spreads to the brain^(1-4). Decades before the onset of motor symptoms, patients with PD suffer from constipation and present with circulating T cells responsive to αS, suggesting that peripheral immune responses initiated in the ENS may be involved in the early stages of PD^(1,5-7). However, cellular mechanisms that trigger αS pathology in the...

Blood-brain barrier (BBB) dysfunction is a hallmark of many diseases of the brain, including those that represent the largest healthcare burden (for example, Alzheimer disease and stroke). Despite this, rejuvenation and repair of the BBB is not a mainstream concept. During life, the BBB is subjected to perturbations and stresses from a wide range of endogenous or exogenous sources, which can promote brain health or can lead to brain pathologies. The BBB supports many functions that are critical...

No abstract

Spatiotemporal changes in the nuclear lamina and cell metabolism shape cell fate, yet their interplay is poorly understood. Here we identify lamin A/C as a key regulator of cysteine catabolic flux essential for proper cell fate and longevity. Its loss in naive mouse pluripotent stem cells leads to upregulation of the cysteine-generating and catabolizing enzymes, cystathionine γ-lyase (CTH) and cystathionine β-synthase (CBS), thereby promoting de novo cysteine synthesis. Increased cysteine flux...

Integrated circuits for communications play an enabling role when it comes to outer-space exploration thanks to their small footprint and low weight^(1-3). However, owing to the severe irradiation effects of space energetic particles, the implementation of radiation-tolerant electronic circuits remains a challenge^(4-6). Here we report the observation of the space radiation effect on a satellite-based device and find that atomically thin materials are expected to accumulate minimal...

CONCLUSION: This claims-based frailty prediction model showed reasonable performance and prognostic value. It may support efficient, population-level frailty screenings where questionnaire-based assessments are impractical.

Serial multi-omic analysis of proteome, phosphoproteome, and glycoproteome is pivotal for elucidating drug mechanisms, discovering biomarkers, and identifying therapeutic targets. However, simultaneous multi-level post-translational modifications (PTMs) analysis via parallel processing is hampered by laborious, time-consuming procedures and inconsistent reproducibility. We present an integrated Multi-level PTMs-Proteomic Enrichment platform (MuPPE), enabling sequential glycoproteome,...

Environmental differences in genetic effect sizes, namely, gene-environment interactions, may uncover the genetic encoding of phenotypic plasticity^(1-3). We provide a cross-population atlas of gene-environment interactions comprising 440,210 individuals from European and Japanese populations, with replication in 539,794 individuals from diverse populations. By decomposing the contributions from age, sex and lifestyles, we delineate the aetiology of these gene-environment interactions, including...