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Multimodal clocks of human aging

1 week 6 days ago
Human aging is characterized by complex structural and functional decline, but quantifying its heterogeneity and assessing biological age remain challenges. We present the mCAS (multicentric Chinese aging standardized cohort) developed from 2,019 Chinese individuals aged 18-91 years. Integrating high-dimensional clinical, physiological, and molecular-level data, we constructed a three-tiered aging framework: the core capacity clock (CC-clock) to quantify clinical physiological decline, the...
Jiaming Li

Even single-domain decline in physical performance predicts short- and long-term mortality in older adults

1 week 6 days ago
CONCLUSIONS: These results suggest that even decline confined to a single physical performance domain may signal an early transition toward increased vulnerability. Monitoring trajectories of physical performance may therefore help identify older adults at increased mortality risk before more widespread functional deterioration becomes apparent.
Chiara Ceolin

Developmental origins of exceptional health and survival: a four-generation family cohort study

1 week 6 days ago
Descendants of longevity-enriched sibships demonstrate a broad health and survival advantage throughout the life course. However, little is known about manifestations during very early life. Here we show a pattern of lower risk of adverse early-life outcomes in third-generation grandchildren (N = 5637) of Danish longevity-enriched sibships compared to the general population, including infant mortality (Hazard Ratio = 0.53, 95% CI [0.36, 0.77]) and a range of neonatal health indicators. These...
Matthew Thomas Keys

sc-ChromAging: A Single-Cell Chromatin Accessibility-based Clock Decodes Cell-Type-Specific Epigenetic Aging Trajectories

1 week 6 days ago
sc-ChromAging, a chromatin accessibility-based aging clock, was developed using single-cell ATAC-seq from 401 Chinese individuals. It identified CD4⁺ naive T cells as the most accurate predictors of age. This clock linked immune aging with pathways in inflammation, infection, and tumor susceptibility, and connecting chromatin changes to plasma metabolites like triacylglycerols.
Xindi Wei

Scientists found the “holy grail” gene that could one day help humans regrow limbs

1 week 6 days ago
Scientists studying axolotls, zebrafish, and mice have uncovered a shared set of genes that may one day help humans regrow lost limbs. By identifying powerful “SP genes” involved in regeneration, researchers discovered that disabling these genes stopped proper bone regrowth in salamanders and mice. They then used a gene therapy inspired by zebrafish biology to partially restore regeneration in mice, marking a major step toward future treatments that could replace damaged limbs with living tissue instead of prosthetics.

New obesity discovery rewrites decades of fat science

2 weeks ago
Scientists have uncovered a surprising secret hidden inside fat cells that could reshape how we think about obesity and metabolic disease. A protein called HSL, long believed to simply release stored fat when the body needs energy, turns out to have a second job deep inside the nucleus of fat cells—helping keep those cells healthy and balanced. Even more surprising, people and mice missing this protein don’t become obese as expected; instead, they lose fat tissue in a dangerous condition called lipodystrophy.

A common constipation drug shows surprising power to protect kidneys

2 weeks ago
A common constipation drug may have unexpectedly unlocked a new way to slow chronic kidney disease — a condition that affects millions and often leads to dialysis. In a clinical trial involving 150 patients, researchers found that lubiprostone, a medication normally used to treat constipation, helped preserve kidney function in people with moderate CKD. Scientists traced the effect to changes in gut bacteria that boosted production of spermidine, a compound linked to healthier mitochondria and reduced kidney damage.

Lipid dysregulation as a central contributor of neurodegenerative diseases: Emerging therapeutic targets and strategies

2 weeks ago
Lipid homeostasis is essential for preserving the structural integrity and functional capacity of the brain. A diverse array of lipids, including cholesterol, phospholipids, and sphingolipids, has been identified as playing pivotal roles. Dysregulation of lipid metabolism is increasingly recognized as a central pathological mechanism in neurodegenerative diseases, including Alzheimer's Disease, Parkinson's Disease, Amyotrophic Lateral Sclerosis, Huntington's Disease, and Cerebrotendinous...
Jiajie Zhang

Exceptional Longevity Modifying Allele APOE2 Promotes DNA Signaling Pathways Resisting Cellular Senescence in Human Neurons

2 weeks ago
Genome-wide association studies (GWAS) have identified APOE2 allele as linked to exceptional longevity, with carriers exhibiting a reduced risk of Alzheimer's disease (AD). Apolipoprotein E (APOE), a glycoprotein involved in lipid transport, has three major alleles. However, alterations in lipid metabolism alone do not fully explain APOE2's protective effects. In contrast, APOE4 is the strongest genetic risk factor for AD. To investigate how APOE2 promotes neuronal longevity and confers...
Cristian Gerónimo-Olvera

Trehalase-trehalose axis in the human brain: A potential modulator of neuroprotection and neurodegeneration

2 weeks ago
Trehalase, the primary enzyme responsible for the degradation of gastrointestinal trehalose ("mushroom sugar"), is well-characterised in the human gut, but has not been conclusively identified in the human brain. Trehalose itself has shown promise in neuroprotection through diverse molecular mechanisms, including the autophagy-driven clearance of cellular debris and neurotoxic aggregates. However, the mechanisms activating trehalose and its integration into human central nervous system processes...
Kalle Keisu

Muscle-derived Mimecan regulates hypothalamus-brown adipose tissue communication and promotes health and lifespan in mice

2 weeks ago
Inter-organ communication plays a critical role in mammalian aging and longevity control. Here, we identified Mimecan from transcriptomic comparisons between young and aged skeletal muscles. Skeletal muscle-derived Mimecan regulates core body temperature via brown adipose tissue (BAT), which is impaired in aged mice. Skeletal muscle-specific loss- and gain-of-function models demonstrate that Mimecan activates melanocortin 4 receptor (MC4R)-positive neurons in the dorsomedial hypothalamus (DMH)...
Kentaro Mori

Garlic-derived metabolite activates LKB1, promotes adipose eNAMPT secretion, and improves age-related muscle function via hypothalamic signaling

2 weeks ago
Garlic (Allium sativum L.) and its aged extract contain many bioactive compounds that can bring health benefits to humans. Among them, S-1-propenyl-L-cysteine (S1PC) has recently drawn significant attention in the field of nutriceutical research. However, the mechanism of its molecular action has remained poorly understood. Here, we show that S1PC significantly activates liver kinase B1 (LKB1) through enhancing its tertiary complex formation with STRAD and MO25, leading to stimulating the...
Jun-Ichiro Suzuki

Gut microbial signatures for aging-related sarcopenia and dietary links among community-dwelling old-old adults: A metagenomic study

2 weeks ago
CONCLUSION: In old-old adults, we identified distinct gut microbiota signatures associated with sarcopenia. R. lactatiformans and P. faecium emerged as candidate features. The dietary-microbiota correlations suggest potential nutrition strategies. These findings provide a basis for exploring microbiota-based approaches in advanced aging.
Ting Zhang

Exceptional Longevity Modifying Allele APOE2 Promotes DNA Signaling Pathways Resisting Cellular Senescence in Human Neurons

2 weeks ago
Genome-wide association studies (GWAS) have identified APOE2 allele as linked to exceptional longevity, with carriers exhibiting a reduced risk of Alzheimer's disease (AD). Apolipoprotein E (APOE), a glycoprotein involved in lipid transport, has three major alleles. However, alterations in lipid metabolism alone do not fully explain APOE2's protective effects. In contrast, APOE4 is the strongest genetic risk factor for AD. To investigate how APOE2 promotes neuronal longevity and confers...
Cristian Gerónimo-Olvera

Liquid-derived, solvent-free vapor-mediated dimensional reconstruction yields a record fill factor in inverted perovskite solar cells

2 weeks ago
Despite recent advances, the fill factor (FF) of perovskite solar cells remains limited, largely owing to defect-related recombination. Paradoxically, most defect passivation approaches still depend on solvents, which deteriorate stability and pose challenges for large-scale fabrication. Here, we introduce a vapor-phase deposited from a liquid triethylammonium pentafluoropropionate (TEA-PFP) layer on top of perovskite. During deposition, TEA⁺ reacts with residual PbI(2) to generate a...
Yinjiang Liu

Circulating levels of insulin-like growth factor binding protein 7 are associated with risks of chronic diseases and death

2 weeks ago
Relationships between the concentration of circulating IGFBP-7 and risk of disease and mortality have been suggested by small-scale investigations. In this prospective study, we investigated these relationships among 53,003 UK Biobank participants. Higher IGFBP-7 level was significantly associated with increased risk for liver cancer, all-cause mortality, diabetes, and other diseases. Associations were robust across sex and age groups and persisted over long follow-up. IGFBP-7 polygenic risk...
Zhi Li

Calibrating T cell responsiveness through interactions with self

2 weeks ago
During an immune response, T cells face one of the most consequential decisions of their lifespan upon recognition of a ligand they have not previously encountered: whether to exit the naive basal state, undergo clonal expansion and acquire effector functions. This process is often portrayed as a binary switch, in which naive cells from a highly diverse repertoire transition from an 'off' state to an 'on' state. However, this digital view overlooks the crucial prior information that T cells...
Judith N Mandl