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Remove subsidies to solve India’s fertilizer-overuse problem
AlphaFold 3 is great — but it still needs human help to get chemistry right
Advising policymakers can’t be taught — researchers must learn by doing
Philanthropic foundations must step in to shield science from Trump’s cuts
How should we test AI for human-level intelligence? OpenAI’s o3 electrifies quest
New Zealand’s giant birds feasted on colorful, trufflelike fungi, fossil poop reveals
The extinction of moa may have left native fungi with no way to spread their spores
Is obesity a disease? Not always, new expert report says
A more scientific definition of obesity should guide decisions about weight loss treatment, researchers argue
Gene editor may have cured infant of a deadly metabolic disorder
Result could be first success at stitching a curative gene into a chromosome’s “safe harbor,” reducing cancer and other risks
Copy cats: Kitties mirror each other’s faces to get along
The behavior—also seen in humans and other social animals—is a key to bonding
The emerging role of oxygen redox in pathological progression of disorders
Neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and Huntington disease, pose serious threats to human health, leading to substantial economic burdens on society and families. Despite extensive research, the underlying mechanisms driving these diseases remain incompletely understood, impeding effective diagnosis and treatment. In recent years, growing evidence has highlighted the crucial role of oxidative stress in the pathogenesis of various neurodegenerative...
Association Between Multimorbidity and End-of-Life Outcomes Among Middle-Aged and Older Adults: Evidence From 28 Countries
CONCLUSIONS AND IMPLICATIONS: Our findings underscore the significant impact of multimorbidity on end-of-life experiences and highlight the importance of coordinated care strategies to address the complex needs of patients with multimorbidity and alleviate their symptom burden.
Genome-wide association study unravels mechanisms of brain glymphatic activity
Brain glymphatic activity, as indicated by diffusion-tensor imaging analysis along the perivascular space (ALPS) index, is involved in developmental neuropsychiatric and neurodegenerative diseases, but its genetic architecture is poorly understood. Here, we identified 17 unique genome-wide significant loci and 161 candidate genes linked to the ALPS-indexes in a discovery sample of 31,021 individuals from the UK Biobank. Seven loci were replicated in two independent datasets. Genetic signals...
Increased SOAT2 expression in aged regulatory T cells is associated with altered cholesterol metabolism and reduced anti-tumor immunity
Immune functions decline with aging, leading to increased susceptibility to various diseases including tumors. Exploring aging-related molecular targets in elderly patients with cancer is thus highly sought after. Here we find that an ER transmembrane enzyme, sterol O-acyltransferase 2 (SOAT2), is overexpressed in regulatory T (Treg) cells from elderly patients with lung squamous cell carcinoma (LSCC), while radiomics analysis of LSCC patients associates increased SOAT2 expression with reduced...
Early prediction of healthy ageing and age-related diseases using blood protein biomarkers
No abstract
Longitudinal serum proteome mapping reveals biomarkers for healthy ageing and related cardiometabolic diseases
The blood proteome contains biomarkers of ageing and age-associated diseases, but such markers are rarely validated longitudinally. Here we map the longitudinal proteome in 7,565 serum samples from a cohort of 3,796 middle-aged and elderly adults across three time points over a 9-year follow-up period. We pinpoint 86 ageing-related proteins that exhibit signatures associated with 32 clinical traits and the incidence of 14 major ageing-related chronic diseases. Leveraging a machine-learning...
Somatic mutation as an explanation for epigenetic aging
DNA methylation marks have recently been used to build models known as epigenetic clocks, which predict calendar age. As methylation of cytosine promotes C-to-T mutations, we hypothesized that the methylation changes observed with age should reflect the accrual of somatic mutations, and the two should yield analogous aging estimates. In an analysis of multimodal data from 9,331 human individuals, we found that CpG mutations indeed coincide with changes in methylation, not only at the mutated...
Epigenetic ageing clocks: statistical methods and emerging computational challenges
Over the past decade, epigenetic clocks have emerged as powerful machine learning tools, not only to estimate chronological and biological age but also to assess the efficacy of anti-ageing, cellular rejuvenation and disease-preventive interventions. However, many computational and statistical challenges remain that limit our understanding, interpretation and application of epigenetic clocks. Here, we review these computational challenges, focusing on interpretation, cell-type heterogeneity and...
Lifetime risk and projected burden of dementia
Understanding the lifetime risk of dementia can inform public health planning and improve patient engagement in prevention. Using data from a community-based, prospective cohort study (n = 15,043; 26.9% Black race, 55.1% women and 30.8% with at least one apolipoprotein E4 (APOE ε4) allele), we estimated the lifetime risk of dementia (from age 55 years to 95 years), with mortality treated as a competing event. We applied lifetime risk estimates to US Census projections to evaluate the annual...
The impact of co-housing on murine aging studies
Analysis of preclinical lifespan studies often assume that outcome data from co-housed animals are independent. In practice, treatments, such as controlled feeding or putative life-extending compounds, are applied to whole housing units, and as a result, the outcomes are potentially correlated within housing units. We consider intra-class (here, intra-cage) correlation in three published and two unpublished lifespan studies of aged mice encompassing more than 20,000 observations. We show that...
Higher Intron Retention Levels in Female Alzheimer's Brains May Be Linked to Disease Prevalence
Multimodal study of Alzheimer's disease (AD) dorsolateral prefrontal cortex (DLPFC) showed AD-related aberrant intron retention (IR) and proteomic changes not observed at the RNA level. However, the role of sex and how IR may impact the proteome are unclear. Analysis of DLPFC transcriptome showed a clear sex-biased pattern where female AD had 1645 elevated IR events compared to 80 in male AD DLPFC. Increased IR is correlated with lower mRNA levels, suggestive of nonsense-mediated mRNA decay. Two...