Summary Antioxidant-rich diets affect telomere length, an integrative marker associated with age-related diseases. Yogurt exerts antioxidative capacity and is speculated to support healthy ageing. However, direct experimental evidence is missing. Here, the effects of yogurt and dairy-fermenting bacteria on D-galactose-induced ageing mice and chemically challenged HepG2 cells were evaluated. Relative telomere length (RTL) in leucocyte and liver were significantly longer in yogurt (1.21 ± 0.07; 1.23 ± 0.11) and Streptococcus thermophilus group (1.18 ± 0.15; 1.13 ± 0.12). When t -BHP-challenged HepG2 cells were treated with digested yogurt and S. thermophilus , the senescence index (13.67 ± 3.30; 19.67 ± 2.87) were lower and RTL (1.25 ± 0.11; 1.18 ± 0.10) were longer than the model. Antioxidative effects were observed for yogurt and S. thermophilus metabolites, whereas milk and Lactobacillus rhamnosus metabolites showed minimal influence on RTL and oxidative stress. In conclusion, this study showed that yogurt and S. thermophilus metabolites ameliorated telomere attrition in ageing mice and t -BHP-challenged HepG2 cells, possibly by reducing oxidative stress.
Aims Di (2-ethylhexyl) phthalate (DEHP), as an environmental endocrine-disrupting chemical (EDC), can induce male reproductive injury. N6-methyladenosine (m6A) plays a vital role in environmental exposure-induced diseases by regulating gene expression. Therefore, we aim to investigate the role of m6A in DEHP-induced reproductive injury. Main methods We established an in vivo model of mice exposed to DEHP to explore the effect of DEHP on reproductive injury and m6A. To further explore the molecular mechanism of DEHP toxicity, we built a model of GC-2 cells exposed to mono-(2-ethylhexyl) phthalate (MEHP) in vitro and further silenced Mettl3 in GC-2cells. Besides, we also conducted MeRIP-qPCR and RIP assays to identify the target genes for m6A modification. Key findings DEHP induced testicular injury and senescence. And telomeres shortening, reduced levels of telomere repeat–binding factor 1 (TRF1), TRF2, protection of telomeres 1 (POT1), and telomerase reverse transcriptase (TERT) can be observed in DEHP-treated testes. MEHP also induced GC-2 cellular senescence and telomere dysfunction. Besides, increased m6A mediated by METTL3 stabilized homeobox containing 1 ( Hmbox1 ) in an m6A-dependent manner in MEHP-exposed GC-2 cells. Mettl3 knockdown led to lower m6A modification and reduced Hmbox1 stability, resulting in further shortening of telomere length. Significance our work uncovered that DEHP led to male reproductive injury by telomere dysfunction and m6A modified Hmbox1 contributed to maintaining telomere homeostasis in this process, suggesting that accurate regulation of m6A modification level by drugs has potential value in the treatment of DEHP-induced male reproductive injury.
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