Globally, throughout human history, a significant increase in the aging population has been observed over the past two decades. According to the World Health Organization (WHO), a trend towards human longevity has been observed, as evidenced by the increase in life expectancy from 66.8 years in 2000 to 73.4 years in 2019. . Increased life expectancy often correlates with improved quality of life. However, the prevalence of age-related diseases, especially neurodegenerative diseases associated with oxidative stress such as Alzheimer’s disease and Parkinson’s disease, increases (Soo et al., 2020). As a result, we expect to see an increase in the global economic burden and a decline in the quality of life. Furthermore, neurons are known to be post-mitotic cells and cannot be replaced once damage occurs, making them highly sensitive to oxidative stress (Grimm & Eckert, 2017). Therefore, interventions that promote healthy aging are a promising research endeavor to modulate the biological processes of aging and protect against these devastating neurodegenerative diseases.
Human aging requires long-term measurements that typically take decades, making it impractical to conduct long-term studies. Therefore, to address this scenario, preclinical models such as cellular senescence represent a promising approach to study the aging process (de Magalhaes, 2004, Roda et al., 2023, Roda et al., 2022). Conclusive evidence has been documented that senescent cells (SCs) are abundant in aging organisms and cause age-related pathologies, and that ablation of SCs serves as a potential therapeutic target (Idda et al. ., 2020, Naylor et al., 2013). Non-replicative stress is the most common method used to induce cellular senescence. Normal or immortalized cells are transformed into senescent cells after exposure to various types of stressors, including chemical and physical factors that induce oxidative stress, mitochondrial dysfunction, or DNA damage (Debacq- Chainiaux et al., 2016, Zia et al., 2022). Tert-butyl hydroperoxide (t-BHP) has been shown to be effective in various cell types such as fibroblasts (Wedel et al., 2020), chondrocytes (Xu et al., 2021), and endothelium (Unterluggauer et al., 2021). It is widely used to induce cellular senescence in cells. , 2003), retinal pigment epithelium (Manoharan et al., 2022) and neurons (Sodero et al., 2011) by inducing oxidative damage to cells. This is due to its oxidative stress-inducing properties and the fact that the root cause of most age-related diseases is due to the accumulation of reactive oxygen species (ROS), which coincides with aging. is a well-accepted model. Mitochondrial theory of aging (Apparao et al., 2022). SC is highly induced by age-related pro-oxidants. Functional foods containing high antioxidant compounds may act as anti-aging agents that regulate the aging process. Since the past decades, cancer (Park, 2022), cardiovascular diseases (Krittanawong et al., 2021), diabetes (Das et al., 2022) and neurodegenerative diseases (Abitbol et al., 2022, Phan et al. ., 2015). Mushrooms are a good source of primary and secondary metabolites such as riboflavin, selenium, vitamin D, beta-glucan, erinacin, herisenone, and ergosterol (Corana et al., 2019, Elkhateeb and Daba, 2022).
Of particular interest, ergothioneine (EGT) is a naturally occurring amino acid known to be one of the most powerful dietary antioxidants found in common foods such as oat bran, grains, and chicken liver. I am. However, early studies have demonstrated that mushrooms contain the most sources of EGT compared to other foods (Ey et al., 2007, Kalaras et al., 2017) . Therefore, it is noteworthy to study the role of mushrooms as a major source of antioxidant-rich foods. EGT is produced only by certain fungi and bacteria and is therefore only available from dietary sources (Pfeiffer et al., 2011). EGT has also received special attention as a potential antioxidant due to the presence of the specific cation transporter type 1 (OCTN1), also known as ergothioneine transporter (ETT) (Gründemann, 2012). ETT is found in various tissues, such as the small intestine, brain, kidney, and bone marrow, and efficiently transports EGT throughout the body (Gründemann et al., 2022). The most notable role of EGT is that it does not undergo autoxidation, unlike other antioxidants such as glutathione, due to its stability due to its existence in the thiol-thione tautomeric form (Cheah & Halliwell, 2012 ). Also, mounting evidence shows that EGT is a powerful scavenger of free radicals (Franzoni et al., 2006, Han et al., 2021), an anti-inflammatory agent (Ito et al., 2011), and an anti-aging agent (Paul ). , 2022).
In our previous study, we were able to demonstrate that EGT protects HT22 cells from neurotoxicity through the antioxidant mechanism of the nrf2 pathway (Kushairi et al., 2020a). In this study, we would like to verify that EGT from mushrooms as a food source is present in sufficient amounts to act as a neuroprotective and anti-aging agent and can exert therapeutic effects within the food matrix of aging HT22 neurons. That’s what I think. The role of EGT underlies various oxidative stress mechanisms; in vitro Although models have been studied, little is known about the role of EGT as an anti-aging compound. However, prior to this study, there had been no attempt to directly measure the effects of extracts containing this compound on neural senescent cells. According to the ‘free radical theory of aging’, increased oxidative stress associated with the aging process causes progressive damage to DNA, proteins and lipids, contributing to age-related diseases, particularly neurodegenerative diseases. Widely accepted. Golden et al., 2002, Hajam et al., 2022). Similarly, antioxidant treatments that reduce oxidative stress may be an important strategy against aging mechanisms. Antioxidant-rich foods have great benefits in promoting healthy aging and preventing age-related diseases. Therefore, to substantiate this speculation, we identified the mushrooms containing the highest EGT levels and investigated the role of EGT-rich mushrooms as anti-aging and anti-aging compounds in hippocampal cells.