Phthalates are commonly used as plasticizers to improve the durability, resistance, and flexibility of polyvinyl chloride (PVC) and other plastic materials. They are one of the most abundant synthetic chemicals, accounting for 65% of plasticizer usage (Larsson et al., 2017). They are commonly used as plasticizers to improve the durability, resistance, and flexibility of plastic materials such as polyvinyl chloride (PVC) and are bound to non-covalent bonds in PVC products (Nardelli et al., 2017; Rowdhwal and Chen, 2018; Zhang et al., 2019). Diethylhexyl phthalate (DEHP) (Fig. 1a) and diisononyl phthalate (DINP) (Fig. 1b) are the most commonly used phthalates and are important components in a wide range of plastic materials, including food packaging, children's toys, and medical devices. DEHP can be transferred to the environment from plastic materials and has bioaccumulation effects on organisms (Al-Saleh et al., 2017; Zhang et al., 2019). Therefore, DEHP is recognized as a typical environmental endocrine disruptor and is strongly associated with many toxicities in both people and animals (Hauser and Calafat, 2005; Mariana et al., 2016; Erythropel et al., 2014). Numerous studies on both people and animals have demonstrated that exposure to phthalates can cause a number of harmful health effects. The endocrine system is one of DEHP's most frequent targets because it has been demonstrated to be directly connected to the manufacture of sex hormones, altering hormone levels and causing problems with glucose and lipid metabolism (Parks et al., 2000; Wong and Gill, 2002). A lot of studies demonstrated that metabolic disorders are associated with higher mortality rates and shorter lifespans (Biessels et al., 2008; Okada-Iwabu et al., 2013; Flegal et al., 2013; Magliano et al., 2020).

Aging is the dysfunction of cells, tissues, and organs caused by external and internal factors during organism growth at specific life stages (Qiao et al., 2019). The insulin-like growth factor-1 (IGF-1) signaling (IIS), mammalian target of rapamycin (mTOR), AKT, P53, and silent mating type information regulation 2 homolog-1(SIRT1) pathways have been linked to aging in yeast, worms, flies, and mammals (Kloet, 1813). When insulin or IGF-1 binds to the IGF-1 receptor, it causes phosphatidylinositol-3-kinase (PI3K) to become phosphorylated. This, in turn, stimulates the downstream AKT pathway, which phosphorylates forkhead transcription factors of the oclass (FOXO) and heat shock factor 1 (HSF-1) (Strilbytska and Storey, 2020). The AKT/FOXO pathway is also important to the aging process (Kloet, 1813). The mTOR signaling pathway is implicated in metabolic disease, cardiovascular disease, and the aging process (Bulut-Karslioglu et al., 2016; Cornu et al., 2013). The p53 tumor suppressor protein responds to various cellular stresses, and many studies have found that p53 plays a significant regulatory role in the aging process (Feng et al., 2012; Tyner et al., 2002). Several studies discovered that the hypoxia inducible factor-1 (HIF-1)/heme oxygenase 1 (HO-1) and reactive oxygen species (ROS)/mTOR signaling pathways involved in DEHP exposure induced negative effects in vivo (Hong et al., 2021; Wu et al., 2022). Zhang demonstrated that the signal transducer and activator of transcription 5 A (STAT5A) signaling pathway participates in MEHP-induced oxidative damage in BRL-3 A hepatocytes. (Zhang et al., 2022). However, there have been few investigations on the impact of phthalates on the aging process, and the underlying mechanisms remain unknown.

In biological sciences, the insect Drosophila melanogaster (D. melanogaster) has been widely used as a model organism (Odenthal and Brinkkoetter, 2019; Zhang et al., 2021). D. melanogaster, as an in vivo model, performs well in determining toxicological effects due to its short lifespan, high fertility, and easy identification of male and female individuals (Chifiriuc et al., 2016; Rand et al., 2010; Zhang et al., 2021). Furthermore, approximately 60% of the genes in D. melanogaster are orthologs to mammals, and the increasing use of Drosophila in toxicity studies has even resulted in the emergence of a research field known as Drosophotoxicology (Chifiriuc et al., 2016; Demir, 2020; Rand et al., 2010; Scott and Buchon, 2019). As a result, D. melanogaster is emerging as a useful model for studying aging and signal pathways (Bilen and Bonini, 2005; Fox et al., 2020). To investigate whether DEHP and DINP could accelerate the aging progress of D. melanogaster, we analyzed the toxicity of DEHP and DINP exposure on the lifespan and aging of D. melanogaster fed with a normal diet or HFD. Moreover, to explore the underlying mechanisms involved in the effect of DEHP and DINP exposure on the lifespan of D. melanogaster. we also introduced the gene linked to the aging-related signal pathway knockout flies to test the lifespan of D. melanogaster. We demonstrated that exposure to DEHP and DINP reduces the lifespan, vitality, and fecundity of both female and male of D. melanogaster when fed either a regular diet or a high-fat diet. Moreover, the molecule mechanism investigation revealed that akt and foxo were required for the detriment.