Nature aging最新文献

Older adults have been shown to engage more with untrustworthy online content, but most digital trace research has focused on political misinformation. In contrast, studies of health misinformation have largely relied on self-reported survey measures. Using linked survey and digital trace data from a national US sample (n = 1,059), we examine exposure to low-credibility health content across websites and YouTube. Here we show that the overall exposure to low-credibility health content is limited but increases with age and is not solely driven by the volume of health-related browsing. Importantly, those who believe inaccurate health claims are more likely to encounter low-credibility content, suggesting that exposure is not merely incidental. While older adults consume less content on YouTube overall, a higher proportion of what they view is from low-credibility sources. Additionally, individuals who consume low-credibility political news are significantly more likely to encounter low-credibility health content. This suggests a shared consumption profile that spans topics and platforms. These results raise new concerns about how online communication environments may potentially shape public health and well-being.

Different neuron types show distinct susceptibility to age-dependent degeneration, yet the underlying mechanisms are poorly understood. Here we applied aging clocks to single neuron types in Caenorhabditis elegans and found that distinct neurons differ in their biological age. Ciliated sensory neurons with high neuropeptide and protein biosynthesis gene expression show accelerated aging and degeneration, correlating with loss of function, which could be prevented by pharmacological inhibition of translation. We show that the C. elegans neuronal aging transcriptomes correlate with human brain aging patterns and anticorrelate with geroprotective interventions. We performed an in silico drug screen to identify potentially neuroprotective small molecules. We show that the natural occurring plant metabolite syringic acid and the piperazine derivative vanoxerine delay neuronal degeneration, and propose these compounds as neuroprotective interventions. Furthermore, we identify neurotoxins that accelerate neurodegeneration, indicating that distinguishing aging trajectories between neuron types can inform on protective interventions as well as risk factors.

Platinum-based chemotherapy is commonly used for non-small cell lung cancer (NSCLC) and high-grade serous ovarian cancer (HGSOC) treatments, yet clinical outcomes remain poor. Cellular senescence and its associated secretory phenotype (SASP) can have multiple tumor-promoting activities, but both are largely unexplored in these cancers. In this study, using xenograft, orthotopic and Kras^G12V-driven murine NSCLC models, we demonstrate that cisplatin-induced senescence strongly promotes malignant phenotypes and tumor progression, which is stimulated by aging. Mechanistically, we found that a transforming growth factor-beta (TGFβ)-enriched SASP drives pro-proliferative effects through TGFBR1 and AKT/mTOR. TGFBR1 inhibition with galunisertib or senolytic treatment reduces tumor progression driven by cisplatin-induced senescence, and concomitant use of TGFBR1 inhibitors with platinum-based chemotherapy reduces tumor burden and improves survival. Finally, we validate the translational relevance of tumor-promoting TGFβ-enriched SASP using clinical NSCLC and HGSOC samples from patients who received neoadjuvant platinum-based chemotherapy. Together, our findings identify a potential cancer therapy resistance mechanism and provide preclinical proof of concept for future trials.

Cellular senescence contributes to aging and disease, and senolytic drugs that selectively eliminate senescent cells hold therapeutic promise. Although over 20 candidates have been reported, their relative efficacies remain unclear. Here we systematically compared 21 senolytic agents using a senolytic specificity index, identifying the Bcl-2 inhibitor ABT263 and the BET inhibitor ARV825 as most effective senolytics across fibroblast and epithelial senescence models. However, even upon extended treatment with these most potent senolytics, a proportion of senescent cells remained viable. We found that senolytic resistance was driven by maintenance of mitochondrial integrity through V-ATPase-mediated clearance of damaged mitochondria. Imposing mitochondrial stress via metabolic workload enhanced the senolytic efficacies of ABT263 and ARV825 in vitro, and in mouse models, ketogenic diet adoption or SGLT2 inhibition similarly potentiated ABT263-induced and ARV825-induced senolysis, reducing metastasis and tumor growth. These findings suggest that mitochondrial quality control is a key determinant of resistance to ABT263-induced and ARV825-induced senolysis, providing a possible framework for rational combination senotherapies.

Cardiac aging is a major driver of cardiovascular diseases and associated mortality, yet its therapeutic options are limited. While long interspersed nuclear element-1 (LINE-1) retrotransposons are known to drive cellular senescence, their role in cardiac aging is poorly defined. Here we showed that LINE-1 expression increased in the heart with age. To investigate their role in cardiac aging, we generated cardiomyocyte-specific Mov10-knockout mice, which failed to suppress LINE-1. These mice developed LINE-1 derepression, cardiac dysfunction and premature cardiac aging by 3 months of age, accompanied by cGAS-STING activation. Pharmacological inhibition of LINE-1 reverse transcription (with 3TC) or STING (with H-151) suppressed cGAS-STING activation and attenuated senescence in Mov10-knockout H9C2 cells. Notably, both inhibitors improved cardiac function and reduced cardiac inflammation and senescence phenotypes in naturally aged mice. Together, our findings establish LINE-1 as a driver of cardiac aging via cGAS-STING activation, highlighting LINE-1 and its downstream effectors as therapeutic targets for age-related cardiac dysfunction.