This years biggest breakthroughs in longevity (2024 edition) !!!

Hello and welcome to my favorite time of the year, the big longevity summary video of 2024. Massively influenced by what I read myself or find most interesting and important. As always, I have divided the articles and topics into sections so that they can jump between them more easily. However, I advise against doing this because I find all parts interesting. Since I now live in Japan, where Yamanaka has conducted research into induced puropotent stem cells, there is no better place to start the video than with stem cells. These cells are able to constantly divide themselves, but also to turn into specialized cells due to their ability of interest. Yamanaka discovered a way to turn specialized cells back into stem cells, by expressing the Yamanaka factors in 4 genes. This refers to what happens during development. And in fact, this first article, which I show, is about a work that was mainly carried out in Osaka and Kyoto and in which puropotent stem cells from coral epithelium were won for transplantation, an in-depth, open, first interventional study on humans in Japan. In the study, they used human-induced proline stem cells to create coral epithelial cell layers, which they could then use as a regenerative medical approach to treat the lack of lymphatic stem cells. What you see now is the procedure. Excuse me, maybe I should have warned you, but so far it has not caused any negative effects on the patients, and that over a period of two years. After a year, they already found that the corneal skin had become less cloudy and the visibility corrected in the distance. A larger clinical study is planned to further investigate the effectiveness of this procedure. Really amazing! But where do these stem cells come from? Well, in Japan they have now set up a clinical HLO bank, which corresponds to about 40% of the Japanese population, so that it can easily be used as a resource for regenerative medical approaches. However, it turns out that it could actually be possible to gain human-induced proline stem cells from people of all ages. In this study, they showed that stem cells from 100-year-olds and their children can be used to build a longevity-specific bank of induced puropotin stem cells. This groundbreaking study has created a valuable tool for examining the mechanisms of healthy aging and resistance to age-related diseases, which may lead to new therapeutic strategies to promote longevity. Another interesting clinical study on humans with stem cells was carried out this year, but this time no induced proprine stem cells were used from a biobank, but an alternative approach, namely the patient's own cells. In this scientific work on the transplantation of chemically induced puropotin stem cells, which were obtained from islands under the anterior rectum of the stomach in a type minus 1 diabetes, chemically induced puropotin stem cells were used. Instead of the gene expression approach with Yamanaka factors, laboratories have previously found a series of chemicals with which they can treat cells to achieve the same effect, so-called chemically induced puropotin stem cells. I will not go into detail how exactly they achieve this with the chemicals, because I already have a complete video on this, but you can divide it into four steps, in which you change the chemical composition in the media, inhibit or activate the various biological pathways within the cell. Let's take a look at their application instead. This published study reports on the successful transplantation of these chemically induced stem cells in a type minus 1 diabetes patient. It is based on work that they previously published on non-human primates. After this introduction of stem cells, the patient reached insulin dependence 75 days after implantation and had significantly improved blood sugar control. The cool thing is that it is also about autologous. This diagram shows how they took the metabolic stem cells obtained from fatty tissue from the patient, converted them into chemically induced puropotin stem cells, differentiated them into island-like cells and then injected them back into the same patient. Of course, this also helps to reduce a possible immune response. Now it is worth considering whether there is an advantage of the chemical compared to the reprogramming based on the Yamanaka factor, but at the moment I have no real opinion on this. Let's stay a little longer with clinical studies on humans and look at the skin this time. In this work, the ectopic fibroblast injection is used to change the skin identity. They took fibroblasts from the patient's soles and injected them into the thighs and observed a stronger thickening of the skin. In other words, the identity of the thigh tissue was changed much more by the skin on the feet. Here, however, they wanted to use this technique to increase the skin thickness in patients who have tissue stumps after an amputation. This concept of identity change or, in other words, a form of cellular reprogramming could be applied to old and young tissue. Maybe my imagination is too broad, but I think that the questions that this work raises are very important. But let's go from the skin to the ovaries. Okay. What are you doing, Nancy? I am researching the improvement of fertility rates in the old age by examining mice. Weddings? Yes, but of course not with mice. With mice, we restore the egg cells of young and old mice to increase fertility. I should have asked you to do that. You did. Here I am. But my research is only about improving fertility rates. I wished you wouldn't have refused. I did. Really? Not. In fact, we were able to quadruple the life expectancy of older mice. And it's true. Colin may be the god of sex, but fertility decreases with age, as is well known. And a groundbreaking study by researchers at the National University of Singapore showed this year that older mice can be rejuvenated in a young follicle environment by transplantation, as you can see here. This process improved mitochondrial function, reduced chromosome anomalies and quadrupled the life expectancy of mice. The importance of the environment for the egg cells is well covered by another fascinating discovery. Many of the proteins in the egg cells are extraordinarily long-living. A study published in E-Life showed that egg cells contain an extremely high number of long-living proteins. More than other tissues and even more than the brain. These stable proteins are not only found in the egg cells themselves, but also in other seed cells in the egg cells. And many of these long-living proteins have protective functions such as DNA repair or cell protection against damage. Interestingly, the concentration of many long-living proteins in the ovum and in the egg cells decreases with age. This gradual disappearance of long-living proteins from ovum and egg cells could explain why fertility decreases in female mammals after a certain age and provide a total of new insights into the mechanisms of reproductive aging and potentially new ways for the development of treatments for treatment of age-related fertility problems in humans. Research into both ovum rejuvenation and long-living proteins in the egg cells could thus pave the way for innovative treatments for fertility, which may increase the reproductive life span of women or improve the success rates of assisted reproduction technologies. But what exactly is aging? Of course we have the characteristics of aging that give us a framework to discuss processes related to aging. But what is it anyway? Well, unfortunately a disappointing realization. It seems that the leading minds in the field of longevity cannot agree on this answer either. A comprehensive survey conducted by Fedim Cladio and colleagues and published this year gave considerable differences of opinion among researchers on basic aspects of aging and clarified the ongoing challenges in defining aging, its causes and its beginning, which underlines the complexity of the field. However, Cladio says that the great variety of answers reflects the many unknowns in this field. He expects rapid progress in the efforts to define aging, including the development of biomarkers for tracking the biological age. It is a time of possibilities. However, there were a few studies this year that tried to answer this question of why we age. I have treated a study in which the non-linearity of aging was examined, in which they identified important changes in molecular markers at the age of about 44 and 60 years. These more dramatic changes were associated with immune regulation, metabolism and the risk of disease. In addition, they use advanced mitomics profiles and thus question the conventional view of aging as a linear process, as they assume that significant physiological changes occur in certain age groups. At the same time, another study was published, which described a proteomic aging. The scientists were able to determine which proteins changed with age and then use this information to reverse the aging process. They found that proteins that contribute most to aging are involved in numerous biological functions, including interactions with the extracellular matrix, immune responses and infections, hormone regulation and reproduction, neuronal structure and function, as well as development and differentiation. Obviously a whole series of processes, but as I explained in this video, both studies raise more questions than they answer. However, it is worth mentioning that immune regulation appears in both studies, and we will look at that next. Let's start with this work. IgG is an aging factor that promotes the fibrosis of the fat tissue and the metabolism. In this study, they found that the accumulation of IgG antibodies promotes tissue fibrosis and impairs metabolic health in mice. Interestingly, they found that a calorie restriction reduces this age-related IgG accumulation, which indicates a potential mechanism for the anti-aging effect of nutritional interventions. In continuation of this topic, another study was published this year. The spatial transcriptional landscape was examined under globulin-associated secretion as a sign of aging, where it turned out that it is not just about the fat tissue, but possibly about many tissues in which we can see this deposition. And in this work they correlated this deposition with the existence of secretion cells or secretion-sensitive cells, as they call them. At least this seems to be the conclusion of this mammoth work, which carried out spatial transcriptional imaging of various mouse tissues. So this suggests that these self-regulating antibodies are at least bad in relation to aging. But can we also use antibodies to extend the lifespan? So-called anti-aging antibodies? Well, maybe we can. This study, which was published at the beginning of the year, showed that the deposition of myoid hematopoietic stem cells by antibodies can protect mice from age-related immune weakness. It is based on an abundance of earlier data. In young mice, there is a balance between two types of blood stem cells, each of which provides another arm of the immune system. The adaptive arm produces antibodies and T-cells, which target certain pathogenic pathogens, and the innate arm generates extensive reactions, such as inflammation of infections. It seems that with increasing age, the latter arm tends to shift. Therefore, the researchers decided to develop antibodies that could bind to these blood stem cells to decimate them and increase the frequency of the adaptive arm. After this treatment, they were able to restore the immune system of the mice and also reduce inflammation. So we have just seen how antibodies can be used to reduce cells, but they can also be used to lower the protein level. Scientists have found that the inhibition of protein interleukin-11 can significantly increase the healthy lifespan of mice. This breakthrough resulted from a study published in Nature, which showed that the inhibition of interleukin-11 signaling by antibody treatments can increase both the health span and the lifespan. In fact, treatments with these antibodies extended their average lifespan by 22.4% in males and 25% in females from the age of 75 weeks. These mice did not only live longer, but also showed a lower incidence of cancer and other age-related diseases, which leads to an improvement of the general health condition. In contrast to these quite large changes in the lifespan, this newer study on lecithin acids, LCA phenotypes and anti-aging effects of calorie restriction also showed some consistent, if not significant, increases in the average lifespan of mice. And that if the mouse LCA was administered from the age of one year. But since we are already talking about studies on lifespan, it is time to take a look at the latest updates of the Interventions test program. As you can see from this table, The results show that 16-alpha-hydroxyoestriol and Candida had the most significant positive effects on the lifespan of men, but some of them also had negative effects on the lifespan of women. And this mentality unfortunately fits this last article, the improbability of a radical life extension in humans in the 21st century. This work tries to bring the former radical improvements of the human lifespan in accordance with improved public health and medicine with the much slower changes today and raises the question of how much longer people can live. And as stated in the title, they suggest that it is unlikely that there would be a radical life extension in this respect. The ITP results in combination with this last study seem to be a negative conclusion. And to be honest, I don't understand the mass here enough to fully understand how realistic these predictions are. But instead, I see it as a new challenge and a reminder that we have to work more intelligently and more ambitiously on longevity. And together with my knowledge, which of course I cannot put into a single video, I remain optimistic and hope to be able to make even more scientific contributions in the future. So that's it with my very preconceived views on longevity research in 2024, in which many, many, many articles were overlooked. I'm really sorry if I missed your research results. Please comment below what I missed. And with that I only have one thing to say. Happy New Year!