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Aging is related to a progressive decline in physiological functions and is affected by environmental factors. Metal exposures are linked with many health effects, but have poorly understood associations with aging. In this study, a total of 33,916 participants from the Dongfeng-Tongji cohort were included to establish biological age (BA) predictors by using recent advanced algorithms, Klemera and Doubal method (KDM) and Mahalanobis distance. Two biological aging indexes (BAIs), recorded as KDM-accel [the residual from regressing KDM-BA on chronological age] and physiological dysregulation (PD), were separately defined and tested on their associations with mortality by using Cox proportional hazard models. Among 3320 subjects with laboratory determinations of 23 metals in plasma, the individual and overall associations between these metals and BAIs were evaluated by using multiple-linear regression and weighted quantile sum (WQS) models. Both BAIs were prospectively associated with all-cause mortality among the whole participants [KDM-accel: HR(95%CI) = 1.23(1.18, 1.29); PD: HR(95%CI) = 1.37(1.31, 1.42)]. Each 1-unit increment in ln-transformed strontium and molybdenum were cross-sectionally associated with a separate 0.71- and 0.34-year increase in KDM-accel, and each 1 % increment in copper, rubidium, strontium, cobalt was cross-sectionally associated with a separate 0.10 %, 0.10 %, 0.09 %, 0.02 % increase in PD (all FDR 0.05). The WQS models observed mixture effects of multi-metals on aging, with a 0.20-year increase in KDM-accel and a 0.04 % increase in PD for each quartile increase in ln-transformed concentrations of all metals [KDM-accel: β(95%CI) = 0.20(0.08, 0.32); PD: β(95%CI) = 0.04(0.02, 0.06)]. Our findings revealed that plasma strontium, molybdenum, copper, rubidium and cobalt were associated with accelerated aging. Multi-metals exposure showed mixture effects on the aging process, which highlights potential preventative interventions.

Mitochondria are essential organelles that execute fundamental biological processes, while mitochondrial DNA is vulnerable to environmental insults. The aim of this study was to investigate the individual and mixture effect of plasma metals on blood mitochondria DNA copy number (mtDNAcn).This study involved 1399 randomly selected subcohort participants from the Dongfeng-Tongji cohort. The blood mtDNAcn and plasma levels of 23 metals were determined by using quantitative real-time polymerase chain reaction (qPCR) and inductively coupled plasma mass spectrometer (ICP-MS), respectively. The multiple linear regression was used to explore the association between each metal and mtDNAcn, and the LASSO penalized regression was performed to select the most significant metals. We also used the quantile g-computation analysis to assess the mixture effect of multiple metals.Based on multiple linear regression models, each 1% increase in plasma concentration of copper (Cu), rubidium (Rb), and titanium (Ti) was associated with a separate 0.16% [β(95% CI) = 0.158 (0.066, 0.249), P = 0.001], 0.20% [β(95% CI) = 0.196 (0.073, 0.318), P = 0.002], and 0.25% [β(95% CI) = 0.245 (0.081, 0.409), P = 0.003] increase in blood mtDNAcn. The LASSO regression also confirmed Cu, Rb, and Ti as significant predictors for mtDNAcn. There was a significant mixture effect of multiple metals on increasing mtDNAcn among the elder participants (aged ≥65), with an approximately 11% increase in mtDNAcn for each quartile increase in all metal concentrations [β(95% CI) = 0.146 (0.048, 0.243), P = 0.004].Our results show that plasma Cu, Rb and Ti were associated with increased blood mtDNA, and we further revealed a significant mixture effect of all metals on mtDNAcn among elder population. These findings may provide a novel perspective on the effect of metals on mitochondrial dysfunction.

Osteoarthritis (OA) is a common chronic inflammatory joint disease characterized by cartilage degradation. p-Coumaric acid (PCA), a dietary phenolic compound, has exerted anti-inflammatory and anti-oxidative activities in various diseases. However, the effects of PCA on OA have not been reported. In the present study, we aimed to investigate the effects of PCA on interleukin-1β(IL-1β)-induced inflammatory responses and cellular senescence in rat chondrocytes. Our results revealed that PCA remarkably downregulated IL-1β-induced inflammatory factors such as COX2 and iNOS and cartilage-degrading enzymes like matrix metalloproteinases (MMP1, MMP3, and MMP13) and aggrecanases (ADAMTS4 and ADAMTS5) in chondrocytes. The IL-1β-induced degradation of cartilage matrix (collagen II and aggrecan) could also be suppressed by PCA. Besides, PCA treatment effectively inhibited the IL-1β-induced p16INK4a protein expression and SAβ-gal activities in vitro. Mechanism analysis showed that PCA suppressed IL-1β-induced activation of mitogen-activated protein kinase (MAPK) and nuclear factor-kappaB (NF-κB) pathways. In vivo, we also found that PCA could alleviate the development of OA in a rat model. Altogether, our findings implicate that p-coumaric acid attenuates IL-1β-induced inflammatory responses and cellular senescence via inhibition of the MAPK and NF-κB signaling pathway in chondrocytes, and p-coumaric acid may be a promising candidate for the treatment of osteoarthritis.

Exposure of humans to parabens is widespread and urinary parabens are widely used as exposure biomarkers. However, are the levels of these chemicals suitable to assess exposure to parabens? We conducted an intervention study by controlling the use of personal care products (PCPs) to explore the exposure of parabens. Ten female participants were recruited who were treated with different types of PCPs during the 18-day study period. The concentrations of parabens and their metabolites in matrices of different exposure pathways (dust, drinking water and dietary food) and urine samples were determined. We demonstrated that PCPs were the major sources of parabens, accounting for >99% of total exposure. The metabolites were nonspecific to individual parabens and could not be used as exposure biomarkers. Urinary paraben concentrations were positively correlated with external exposure levels. However, poor reproducibility was observed, with intraclass correlation coefficients (ICC) ranging from 0.125 to 0.295 in unadjusted urinary concentrations. Creatinine-adjusting could not significantly improve the ICC values in random spot samples. After adjusting for both creatinine and kinetic models, the ICC values ranged from 0.695 to 0.886, indicating a good reproducibility. So, toxicokinetic parameters may be taken into consideration for precise monitoring of exposures for the non-persistent pollutants.