Defying Aging #aging #health #longevity #hypoxia #senescence #senolytics # immune system #collagen

The original presentation is available as a PDF file. https://drive.google.com/file/d/1ICWYi3NE2P11Xnaggm95BU4XgM3VK6Wi/view?usp=sharing Компьютерный перевод текста презентации на русский язык также доступен для скачивания по ссылке: https://drive.google.com/file/d/10kQlL4GsDWq8Lg1ZU6jF8aHP9QR77tRn/view?usp=drive_link Join my Telegram channel: https://t.me/OlegKulikov to communicate with me Join your_health_longevity group: https://t.me/+PbE43EFvEFRjYzU9 If you think humans deserve to live a long, healthy, and productive life and have a galactic future, you may support my project: https://buymeacoffee.com/drolegkulikov To keep this project growing, I’m looking to upgrade my equipment and software to keep an online server and train AI on my materials to answer your questions without any delay through a website. Your support would make a huge difference in helping me achieve this goal. In return for your support, I am offering exclusive access to all my materials and presentations, early access to uploaded videos, and my answers to your questions, if you have any. You can personally join my project with Patreon: (https://paypal.me/drolegkulikov?country.x=TH&locale.x=en_GB). or make donations through PayPal: (https://www.paypal.me/IrinaDumic). Don’t hesitate to contact me with proposals and questions by email (oleg.kulikow@gmail.com). Also, subscribe to my channel, share this information with your friends and relatives, and click on a bell button to get notifications on the new content. I am not a medical professional but a Dr. in science and have a PhD in physics and math. While I rely on thorough research of scientific literature and practical experience for personal benefit, I recognize that what works for me may not work for others. Therefore, I don't offer medical advice, but I hope the information and links provided can help others make informed decisions. The use of information on this YouTube channel or materials linked to my project is at the user’s own risk. The aging process is largely driven by the loss of elasticity in the extracellular matrix (ECM), which provides structural support for the cells in our body, and the hardening of blood vessels. This persistently impairs blood circulation and causes low oxygen levels in tissues, known as chronic hypoxia. Under hypoxic conditions, cells switch to producing the energy molecule ATP by anaerobic glycolysis, a less efficient process that does not require oxygen. Low oxygen levels also harm the mitochondria, the organelles that generate most of the ATP in cells and lead to increased production of reactive oxygen species (ROS). ROS are unstable molecules that can damage proteins and cellular membranes in cells. As a consequence of this damage, some cells undergo programmed cell death or apoptosis, and others enter a state of senescence or cellular aging. Senescent cells enlarge and secrete various inflammatory molecules, collectively called the senescence-associated secretory phenotype (SASP). SASP molecules stimulate fibrocytes, the cells that produce collagen, a major component of the ECM. This further increases the local stiffness of the ECM, which in turn induces more cells to become senescent and secrete more SASP. Eventually, high levels of SASP attract immune cells such as macrophages, which are supposed to clear the tissue from dead cell debris, break down excess collagen, and eliminate senescent cells. However, in older age, the immune system is often overwhelmed by various challenges and fails to control the excessive accumulation of senescent cells and the development of fibrosis, which is abnormal tissue scarring due to excess collagen. Naked mole rats (NMRs) are remarkable for their exceptional longevity, with a lifespan exceeding 37 years, compared to just a few years for most other rodents like mice. NMRs live in a hypoxic environment in underground colonies in East Africa and are highly tolerant of hypoxia. These animals have evolved several unique adaptations to resist aging-related pathologies. For instance, NMRs have strong resistance to age-related diseases such as cancer and Alzheimer's disease. One of the factors contributing to their longevity is their ability to resist the accumulation of senescent or "senescent" cells. While they do accumulate senescent cells with age, these cells do not secrete SASP, which is associated with aging-related chronic inflammation. This unique characteristic may contribute to their longevity and ability to resist aging-related pathologies. The removal of senescent cells has been shown to extend the healthy lifespan of mice and alleviate age-related disorders, as demonstrated in a study [DOI: 10.1016/j.cell.2019.10.005]. Interestingly, naked mole rats (NMRs) possess natural mechanisms for eliminating senescent cells. Specifically, NMR fibroblasts are particularly susceptible to the accumulation of hydrogen peroxide (H2O2) in hypoxic conditions, as evidenced by research