Aging & Longevity

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...

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)...

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...

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.

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...

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...

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...

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...

Aging in the mammalian brain involves significant structural, functional, and metabolic changes, including a decrease in glutamate concentration. Glutamate-weighted chemical exchange saturation transfer (gluCEST) MRI provides a non-invasive method for mapping glutamate distribution with high spatial resolution. Collecting data from a large cohort of healthy mice aged 2 to 23 months, scanned in vivo at 17.2 T, we demonstrate that gluCEST can differentiate multiple brain regions, and introduce a...

CONCLUSION: Age-related differences in CMI were more prominent for gait than for memory tasks. Findings support that DT performance incrementally declines with age. Middle-aged and older adults had similar gait destabilization in different DT walking demands, but older adults had higher interference with DT walking of auditory processing demands. Retrieval tasks during walking expose early deficits in middle-aged adults that differentiate them from younger adults. Results further suggest...

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Supplemental oxygen (hyperoxia), often provided to premature infants, can disrupt lung growth and contribute to development of neonatal and pediatric lung diseases, necessitating understanding of underlying mechanisms. We previously showed that even moderate hyperoxia (< 60% O(2)) induces detrimental cellular senescence in 18-22 weeks human fetal airway smooth muscle (fASM), a key cell type in airway contractility and remodeling. In this study, we examined the ability of senotherapeutics...

Among older adults with early breast cancer, the risk of chemotoxicity can vary widely despite similar chronological age. Here, we evaluated whether epigenetic indicators of biological age can stratify the risk of chemotoxicity in this population. In a prospective study of 394 women age > 65 with stage I-III breast cancer treated with neo/adjuvant chemotherapy, we analyzed peripheral blood DNA methylation patterns to estimate epigenetic age acceleration (EAA) before chemotherapy. We tested five...

Aging profoundly alters the neuromotor and cognitive systems that support gait control, leading to increased variability and instability that predict functional decline and dementia risk. In this pilot study, conducted to inform the design of the Semmelweis Study gait assessment pipeline, we examined how aging and cognitive load influence the magnitude and temporal organization of gait fluctuations. The Semmelweis Study is a large, prospective workplace cohort at Semmelweis University designed...

Although plasma pTau181 has been shown to accurately discriminate patients with Alzheimer's disease from healthy older adults, there are few studies of plasma biomarkers among middle-aged populations. Given the potential utility of plasma AD biomarkers such as pTau181 in screening for disease risk, examining pTau181 in a middle-aged cohort without AD is important for future implementation. The objectives of this study were to characterise plasma pTau181 in a middle-aged birth cohort aged 45...

Chronic sympathetic nerve activity (SNA) to end organs plays a crucial role in the pathophysiology of obesity-induced hypertension. Oxidative stress and neuroinflammation in the rostral ventrolateral medulla (RVLM), a key brainstem region regulating sympathetic outflow, have been implicated in the sympathetic overactivity in obesity. However, the upstream mechanisms driving RVLM neuroinflammation remain unknown. We hypothesized that obesity induces cellular senescence, a stress response...

CONCLUSION: Through integrated transcriptomic analysis together with in vitro experimental validation, this study indicates that TMEM140 may be a candidate bridge molecule connecting PD and AD comorbidity. TMEM140 may participate in shaping the peripheral-central immunosenescence network and contribute to the cross-system transmission of inflammatory signaling.

Aging involves morphological and functional changes across different organs, but how these changes are linked among the different organs remains to be elucidated. Here, we uncover a central role of platelets in systemic aging. In aged mice, the levels of platelet-secreted pro-inflammatory factors (PSPF) increased greatly in the serum and platelets, leading to a diffuse increase of platelet infiltration in the brain, liver, lung, kidney, and aortic root. The RNA-binding protein HuR/ELAVL1, a...

Deoxyribonucleic acid provides unmatched information density and longevity for data storage, yet its easy amplification by polymerase chain reaction enables unauthorized replication at negligible cost. We introduce ZAT-DNA, which encodes information in patterns of canonical adenine and noncanonical 2-aminoadenine. As DNA polymerases cannot distinguish adenine from 2-aminoadenine, polymerase-based amplification erases these patterns, enforcing molecular-layer non-replicability intrinsic to the...

By eliciting lung necrosis, which enhances aerosol transmission, Mycobacterium tuberculosis (Mtb) sustains its long-term survival as a human pathogen. In studying the human-like necrotic granuloma lesions characteristic of Mtb-infected B6.Sst1S mice, we found that lung myeloid cells display elevated senescence markers: cell cycle arrest proteins p21 and p16, the DNA damage marker γH2A.X, senescence-associated β-galactosidase activity, and senescence-associated secretory phenotype (SASP). These...