npj aging最新文献

In the subterranean rodent (Nanno)spalax galili, evolutionary adaptation to hypoxia is correlated with longevity and tumor resistance. Adapted gene-regulatory networks of Spalax might pinpoint strategies to maintain health in humans. Comparing liver, kidney and spleen transcriptome data from Spalax and rat at hypoxia and normoxia, we identified differentially expressed gene pathways common to multiple organs in both species. Body-wide interspecies differences affected processes like cell death, antioxidant defense, DNA repair, energy metabolism, immune response and angiogenesis, which may play a crucial role in Spalax's adaptation to environmental hypoxia. In all organs, transcription of genes for genome stability maintenance and DNA repair was elevated in Spalax versus rat, accompanied by lower expression of aerobic energy metabolism and proinflammatory genes. These transcriptomic changes might account for the extraordinary lifespan of Spalax and its cancer resistance. The identified gene networks present candidates for further investigating the molecular basis underlying the complex Spalax phenotype.

The extent of hearing loss requiring hearing aid (HA) to prevent cognitive decline is unclear; we assessed this post-midlife along with the relationship between hearing thresholds and cognitive function in those who had never used HA (non-users) or used HAs for >3 years (long-term users). This study comprised 117 individuals ≥55 years with an average hearing threshold of ≥25 dB HL in their better ear and 55 of the non-users and 62 of the long-term users. The Mini-Mental State Examination, the Symbol Digit Modalities Test (SDMT), and pure-tone and sound-field audiometry were assessed. Mean ± SD hearing levels of the non-user and long-term user group were 40.83 ± 8.16 and 51.13 ± 14.80 dB HL. Non-users showed a significant association (P = 0.01) between the hearing thresholds and SDMT scores, with a cutoff value of above 38.75 dB HL identified as affecting cognitive function. There were no significant associations for long-term users.

Therapy-induced senescence (TIS) alters calcium (Ca²⁺) flux and Mitochondria-ER Contact Sites (MERCS), revealing critical vulnerabilities in senescent cells. In this study, TIS was induced using Doxorubicin and Etoposide, resulting in an increased MERCS contact surface but a significant reduction in ER-mitochondria Ca²⁺ flux. Mechanistically, TIS cells exhibit decreased expression of IP3R isoforms and reduced interaction between type 1 IP3R and VDAC1, impairing Ca²⁺ transfer. This flux is crucial for maintaining the viability of senescent cells, highlighting its potential as a therapeutic target. Inhibition of ER-mitochondria Ca²⁺ flux demonstrates senolytic effects both in vitro and in vivo, offering a novel strategy for targeting senescent cells.

Understanding the impact of early vascular aging (EVA) on acute ischemic stroke (AIS) outcomes may provide new insights for improving prognostic assessments and developing targeted therapeutic strategies. This study aimed to validate the EVA ambulatory score (EVAAs) in AIS patients, assessing its association with stroke type, severity, and prognosis. Among the 2,730 AIS patients with a mean age of 72.0 ± 14.4 years, 83.4% exhibited EVA. EVA was identified as an independent predictor of poor outcome at both discharges (aOR:1.72, 95%CI:1.25-2.36, p < 0.001) and at 90 days (aOR:2.22, 95%CI:1.49-3.31, p < 0.001). In subgroup analyses, EVAAs showed improved predictive value in AIS patients with a lower cardiovascular disease burden and a non-atherogenic lipid profile. The EVAAs, as an indicator of EVA that could be easily integrated into daily clinical practice, are a significant predictor of adverse outcomes in AIS patients.

Cellular senescence is a stress response that limits tumor formation by promoting the removal of damaged cells through the immune system. In this study, we observed accumulation of senescent cells during human aging gingival tissue, by increased levels of γH2A.X, 53BP1, and SAHF, along with a greater distance of H3K9me3 from the nuclear periphery. Additionally, primary gingival fibroblasts from older individuals displayed an enlarged nuclear area and perimeter, accompanied by DNA damage responses and increased Lamin B1 invaginations. The combination of phospho-p38 (Thr180/Tyr182) foci with form factor demonstrated an 79.27% predictive accuracy for aging in gingival fibroblasts, with an AUC of 0.83. In co-culture experiments, our findings revealed that senescent fibroblasts from aged donors exhibit slower and fewer recruitment of PBMCs and decreased levels of the Natural Killer cell receptor ligand MICA/B and the CD112R ligand Nectin-2, suggesting potential impairment in immune surveillance mechanisms during aging.

Ageing is associated with cognitive decline, which is a significant factor in the development of dementia. Vitamin B12 (VB12) is crucial for maintaining proper nervous system function, as well as for protein, fat, and carbohydrate metabolism, and DNA synthesis. Moreover, it helps prevent serious health conditions such as pernicious anemia, neurodegenerative diseases, and Alzheimer's disease. VB12 deficiency is common among the elderly population. We found that serum VB12 levels were significantly elevated in centenarians. Interestingly, VB12 supplementation delayed aging but also improved learning and memory in nematodes. Our results suggest that increasing VB12 activates ptp-3 and helps maintain good cognitive function in centenarians. Furthermore, aging is the gradual decline in bodily functions that impacts nearly all living organisms, with significant effects on salivary glands. Salivary gland degeneration may contribute to VB12 deficiency in the elderly, underscoring the crucial role of salivary regulation in VB12 absorption for centenarians.

An artificial intelligence (AI)-enabled electrocardiogram (ECG) model has been developed in a healthy adult population to predict ECG biological age (ECG-BA). This ECG-BA exhibited a robust correlation with chronological age (CA) in healthy adults and additionally significantly enhanced the prediction of aging-related diseases' onset in adults with subclinical diseases. The model showed particularly strong predictive power for cardiovascular and non-cardiovascular diseases such as stroke, coronary artery disease, peripheral arterial occlusive disease, myocardial infarction, Alzheimer's disease, osteoarthritis, and cancers. When combined with CA, ECG-BA improved diagnostic accuracy and risk classification by 21% over using CA alone, notably offering the greatest improvements in cancer prediction. The net reclassification improvement significantly reduced misclassification rates for disease onset predictions. This comprehensive study validates ECG-BA as an effective supplement to CA, advancing the precision of risk assessments for aging-related conditions and suggesting broad implications for enhancing preventive healthcare strategies, potentially leading to better patient outcomes.