Lifeboat Foundation

A study at the University of Cologne’s CECAD Cluster of Excellence in Aging Research has identified a protein complex that is activated by defects in the spliceosome, the molecular scissors that process genetic information. Future research could lead to new therapeutic approaches to treat diseases caused by faulty splicing.

The genetic material, in the form of DNA, contains the information that is crucial for the correct functioning of every human and animal cell. From this information repository, RNA, an intermediate between DNA and protein, the functional unit of the cell, is generated. During this process, the genetic information must be tailored for specific cell functions. Information that is not needed (introns) is cut out of the RNA and the important components for proteins (exons) are preserved.

A team of researchers led by Professor Dr. Mirka Uhlirova at the University of Cologne’s CECAD Cluster of Excellence in Aging Research has now discovered that if the processing of this information no longer works properly, a protein complex (C/EBP heterodimer) is activated and directs the cell towards a dormant state, known as cellular senescence. The results appear under the title “Xrp1 governs the stress response program to spliceosome dysfunction” in Nucleic Acids Research.

A preventative anti-aging therapy seems like wishful thinking.

Yet a new study led by Dr. Corina Amor Vegas at Cold Spring Harbor Laboratory describes a treatment that brings the dream to life—at least for mice. Given a single injection in young adulthood, they aged more slowly compared to their peers.

By the equivalent of roughly 65 years of age in humans, the mice were slimmer, could better regulate blood sugar and insulin levels, and had lower inflammation and a more youthful metabolic profile. They even kept up their love for running, whereas untreated seniors turned into couch potatoes.

Ageing, as you might expect, had a big impact on participants’ feelings of loneliness. The deaths of partners and loved ones was particularly difficult, while participants also commented on how loss of mobility restricted their social activities. Social skills were also identified as a risk factor: one participant noted that those without strong social skills may be more likely to suffer.

Emotionally, loneliness was (unsurprisingly) connected to feelings of emptiness, sadness and lack of meaning. One participant described herself as feeling “lost… and not having control, and sometimes it can lead you to not be able to make decisions and then it just gets worse”, whilst another described loneliness as “the feeling of nothing”

But many participants also commented on strategies they used to protect against loneliness. Though ageing was a risk factor, acceptance of ageing had more positive outcomes. As one participant put it: “I used to mountain climb… If I can’t walk anymore, I’ll crawl. You have to learn how to be realistic and not brood about it. I know I’m getting older, but I consider life a transition.” Compassion was also useful: being proactive about helping others, for example, helped some participants prevent being lonely.

More deathism from Mr Tyson. Really I’m a big fan but I dislike this sort of thinking. I commented on the vid.

What if we could live forever? Neil deGrasse Tyson takes us through life and death: if we could live forever what would life really mean? We explore why fresh flowers have meaning and why dogs make every day count. Learn about the Cretaceous-Tertiary Event, The Permian-Triassic Extinction, The Holocene Epoc, and how Earth is one killing machine.

Continue reading “Would We Want to Live Forever?” »

Scientists have discovered a mechanism that lets senescent tumor cells undermine chemotherapy. With this mechanism blocked, standard chemotherapy led to complete regression of mammary tumors in mice [1].

Senescent yet still dangerous

Chemotherapy and radiation therapy, still the two most common treatments for solid tumors, subject cells to powerful stress as they are designed to do. This stress drives cellular senescence. Since senescent cells stop proliferating, inducing senescence in cancer cells is considered a desirable outcome. However, this is not the end of the story.

Acetamiprid-induced oxidative stress can harm DNA and tRNA, leading to health problems. A study conducted by Huixia Zhang at Macau University of Science and Technology in 2023 introduced a comprehensive approach to assessing acetamiprid-induced oxidative damage to tRNA in human cells through oxidized nucleotide and tRNA profiling. Acetamiprid, a modern insecticide, is known for causing oxidative stress and related toxicity. Despite its impact on oxidative stress, the effects of acetamiprid-induced oxidative stress on RNA, especially tRNA, remained unexplored until this study.

Acetamiprid was found to elevate reactive oxygen species (ROS) production in HepG2 and LO2 cells, contributing to mitochondrial damage, free radical generation, and antioxidant status depletion. Oxidative damage to DNA and RNA can harm organisms, with prior research addressing RNA damage in aging, neurodegenerative diseases, and mental illnesses. However, its role in acetamiprid-induced toxicities has not been investigated.

The study employed TMSD labeling-based LC-MS/MS to measure oxidized nucleotide levels in HepG2 and LO2 cells treated with two mM acetamiprid. It also examined the impact of acetamiprid on the 8-oxo-G content of tRNAs and created volcano plots to compare RNase T1 digestion products of tRNAs from untreated and acetamiprid-treated cells.

Reverse Aging Revolution

During my pursuits, I’ve come across an increasing number of exciting nontraditional routes for funding scientific research. The efforts of Adam Marblestone and Benjamin Reinhardt have been particularly instrumental in stimulating this ecosystem, but many other great people have contributed as well. These new funding routes are a welcome relief since many of the most innovative and far-reaching projects are not especially suited for receiving governmental NIH, NSF, etc. funding. If you would like to find a more comprehensive list of such alternative funding sources, you should check out https://arbesman.net/overedge/. My own list (below) consists of funding sources that stand out to me as particularly promising. I hope you find this useful and feel free to reach out if you have any questions!

PDF version

Amaranthe Foundation https://amaranth.foundation/bottlenecks-of-aging “We outline initiatives which, if executed, could meaningfully accelerate the advancement of aging science and other life-extending technologies. The resulting document is a philanthropic menu, for which Amaranth is seeking both talent to execute on and co-funders. If you are a founder, researcher, or philanthropist interested in executing or co-sponsoring one or several of the projects or proposals below, please reach out to us”

Cancer treatments, including chemotherapy, in addition to killing a large number of tumor cells, also result in the generation of senescent tumor cells (also called “zombie cells”). While senescent cells do not reproduce, they do, unfortunately, generate a favorable environment for the expansion of tumor cells that may have escaped the effects of the chemotherapy and eventually result in tumor regrowth.

An international team of researchers led by Dr. Manuel Serrano at IRB Barcelona has described in Nature Cancer how cancer cells that have become senescent after chemotherapy activate the PD-L2 protein to protect themselves from the immune system while recruiting immune suppressor cells. The latter creates an inhibitory environment that impairs the ability of lymphocytes to kill cancer cells.

Based on these findings, scientists wondered what would be the effect of inactivating PD-L2. Interestingly, senescent cells lacking PD-L2 are rapidly eliminated by the immune system. This intercepts the capacity of senescent cells to create an immunosuppressive environment and, as a result, lymphocytes retain their full capacity to kill those cancer cells that may have escaped the effects of chemotherapy.