1️⃣ Genomic Instability 2️⃣ Telomere Attrition 3️⃣ Epigenetic Alterations 4️⃣ Loss of Proteostasis 5️⃣ Nutrient Sensing Goes Awry 6️⃣ Mitochondrial Dysfunction 7️⃣ Cellular Senescence 8️⃣ Stem Cell Exhaustion 9️⃣ Altered Intercellular Communication.
Explore these horsemen and the strategies being deployed to defeat this decline in Chapter 10 — The Future of #Longevity ➡️ futurefasterbook.com
Removal of an essential gene was a major contributor to preterm labor, according to recent research.
Researchers from Cincinnati Children’s Hospital Medical Center started with a pathway linked to the tumor suppressor gene known as transformation-related protein 53 (Trp53), which encodes another protein: p53. Mutations of Trp53 are found in a variety of cancers, but the gene’s function in female reproduction and other normal physiological processes is not well understood. The role of p53, sometimes referred to as the “guardian angel gene,” is to help preserve genetic stability and prevent mutation.
The researchers targeted certain signaling pathways that function both in pregnancy and during the formation of cancerous tumors. During pregnancy, the pathways are usually tightly regulated. In tumor development, however, they can become dysfunctional.
Nearly every day, new discoveries are pushing the genetics revolution ever-forward. It’s hard to imagine it’s been only a century and a half since Gregor Mendl experimented with his peas, six decades since Watson and Crick identified the double helix, fourteen years since the completion of the human genome project, and five years since scientists began using CRISPR-cas9 for precision gene editing. Today, these tools are being used in ways that will transform agriculture, animal breeding, healthcare, and ultimately human evolution.
Common practices like in vitro fertilization (IVF) and preimplantation embryo selection make human genetic enhancement possible today. But as we learn more and more about what the genome does, we will be able to make increasingly more informed decisions about which embryos to implant in IVF in the near term and how to manipulate pre-implanted embryos in the longer-term. In our world of exponential scientific advancement, the genetic future will arrive far faster than most people currently understand or are prepared for.
Human genetic science is one of the most important and potentially beneficial advancements of our time, but the monumental health and well-being benefits of these technologies could be overwhelmed by fear, hysteria, and international conflict if a foundation for informed and inclusive public and governmental dialogue is not laid as soon as possible.
Freeman Dyson, renowned scientist and scholar, has died at 96, according to his daughter Mia.
The British-born scientist and professor emeritus spent much of his career as a physics professor at the Institute for Advanced Study in Princeton, according to his biography on the institute’s website. He was among 29 scientists who supported the Obama administration’s 2015 nuclear deal with Iran. In 1967, he also acted as a military adviser regarding the use of tactical nuclear weapons in the Vietnam War, and in 1984 he wrote a book on the dangers of nuclear warfare.
A futurist and space-enthusiast, Dyson had several scientific concepts named after him, including the “Dyson Tree,” a genetically engineered plant that would be able to survive in a comet and grow in space. One of his ideas, the Dyson Sphere, was featured in an episode of the sci-fi series Star Trek.
O.o um what?
Over the past few years biologists have developed several lines of evidence showing that one particular protein molecule inside cells plays an extraordinary variety of life-protecting roles, so much so that the molecule has been dubbed a “guardian angel.” The findings are leading to greater knowledge of how life works and to a deeper understanding of the root causes of cancer.
So pervasive is the molecule’s role that scientists in four areas of biology were on the trail of it, each field unaware, until recently, of the protein’s importance in the others.
Molecular biologists, for example, were trying to learn more about how cells repair the genetic damage that is routinely inflicted by radiation, chemicals and even body heat. In another area of research, cell biologists were trying to understand how cells govern the timing of when they divide. Other cell biologists wanted to know how cells carry out a natural process called “programmed cell death,” or apoptosis, in which a cell literally commits suicide. And, finally, cancer researchers were puzzled by the fact that at least half of all victims had tumors with mutations in one particular gene — so many that they called the gene a “tumor suppressor” on the grounds that when it was knocked out, a cell was predisposed to become cancerous. A Four-Team Effort.
Klotho (KL) is described as an anti-aging gene because mutation of Kl gene leads to multiple pre-mature aging phenotypes and shortens lifespan in mice. Growing evidence suggests that an increase in KL expression may be beneficial for age-related diseases such as arteriosclerosis and diabetes. It remains largely unknown, however, how Kl expression could be induced. Here we discovered novel molecular mechanism for induction of Kl expression with a small molecule ‘Compound H’, N-(2-chlorophenyl)-1 H-indole-3-caboxamide. Compound H was originally identified through a high-throughput screening of small molecules for identifying Kl inducers. However, how Compound H induces Kl expression has never been investigated. We found that Compound H increased Kl expression via demethylation in CpG islands of the Kl gene. The demethylation was accomplished by activating demethylases rather than inhibiting methylases. Due to demethylation, Compound H enhanced binding of transcription factors, Pax4 and Kid3, to the promoter of the Kl gene. Pax4 and Kid3 regulated Kl promoter activity positively and negatively, respectively. Thus, our results show that demethylation is an important molecular mechanism that mediates Compound H-induced Kl expression. Further investigation is warranted to determine whether Compound H demethylates the Kl gene in vivo and whether it can serve as a therapeutic agent for repressing or delaying the onset of age-related diseases.
Keywords: klotho, methylation, Pax4, Kid3, CpG island.
Pre-mature aging phenotypes were eminent in the klotho (Kl)-deficient mice, which have ~ 10 copies of a transgene integrated in the 5’ flanking region of the Kl gene disrupting its expression [1]. The klotho mice die around ~ 2 months of age after birth due to multiple aging-related organ failures [1]. Later, the role of KL in aging was confirmed by the reproduction of the same aging phenotypes in Kl knockout homozygous (Kl −/−) mice [2]. On the other hand, overexpression of KL extends lifespan by 20–30% [2, 3]. The protein products of Kl gene can be divided into two forms: membrane-integrated form of Kl and non-integrated form of Kl which includes secreted and soluble Kl (sKl). These two type of proteins are produced from the two transcripts that arise from a single kl gene due to alternative RNA splicing [4, 5].
The team compared germ-free (sterile) mice and mice with normal microbes. They used a laboratory technique called mass spectrometry to characterize the non-living molecules in every mouse organ. They identified as many molecules as possible by comparing them to reference structures in the GNPS database, a crowdsourced mass spectrometry repository developed by Dorrestein and collaborators. They also determined which living microbes co-locate with these molecules by sequencing a specific genetic region that acts as a barcode for bacterial types.
In total, they analyzed 768 samples from 96 sites of 29 different organs from four germ-free mice and four mice with normal microbes. The result was a map of all of the molecules found throughout the body of a normal mouse with microbes, and a map of molecules throughout a mouse without microbes.
A comparison of the maps revealed that as much as 70 percent of a mouse’s gut chemistry is determined by its gut microbiome. Even in distant organs, such as the uterus or the brain, approximately 20 percent of molecules were different in the mice with gut microbes.
The very nature of the human race is about to change. This change will be radical and rapid beyond anything in our species’ history. A chapter of our story just ended and the next chapter has begun.
This revolution in what it means to be human will be enabled by a new genetic technology that goes by the innocuous sounding name CRISPR, pronounced “crisper”. Many readers will already have seen this term in the news, and can expect much more of it in the mainstream media soon. CRISPR is an acronym for Clustered Regularly Interspaced Short Palindromic Repeats and is to genomics what vi (Unix’s visual text editor) is to software. It is an editing technology which gives unprecedented power to genetic engineers: it turns them into genetic hackers. Before CRISPR, genetic engineering was slow, expensive, and inaccurate. With CRISPR, genome editing is cheap, accurate, and repeatable.
This essay is a very non-technical version of the CRISPR story concluding with a discussion of Gene Drive[1], a biological technique which, when used with CRISPR, gives even greater power to genetic engineers. The technical details go very deep and for those who are interested in diving in, I’ve included a number of useful pointers. At the end, I will very briefly discuss the implications of these two new technologies.
Ogba Educational Clinic
A nightmarish scene was burnt into my memory nearly two decades ago: Changainjie, Beijing’s normally chaotic “fifth avenue,” desolate without a sign of life. Schools shut, subways empty, people terrified to leave their homes. Every night the state TV channels reported new cases and new deaths. All the while, we had to face a chilling truth: the coronavirus, SARS, was so novel that no one understood how it spread or how to effectively treat it. No vaccines were in sight. In the end, it killed nearly 1,000 people.
It’s impossible not to draw parallels between SARS and the new coronavirus outbreak, COVID-19, that’s been ravaging China and spreading globally. Yet the response to the two epidemics also starkly highlights how far biotech and global collaborations have evolved in the past two decades. Advances in genetic sequencing technologies, synthetic biology, and open science are reshaping how we deal with potential global pandemics. In a way, the two epidemics hold up a mirror to science itself, reflecting both technological progress and a shift in ethos towards collaboration.
Let me be clear: any response to a new infectious disease is a murky mix of science, politics, racism, misinformation, and national egos. It’s naïve to point to better viral control and say it’s because of technology alone. Nevertheless, a comparison of the two outbreaks dramatically highlights how the scientific world has changed, for the better, in the last two decades.
