Lifeboat Foundation

Males may have shorter lifespans than females due to repetitive sections of the Y chromosome that create toxic effects as males get older. These new findings appear in a study by Doris Bachtrog of the University of California, Berkeley published April 22 in PLOS Genetics.

In humans and other species with XY sex chromosomes, females often live longer than males. One possible explanation for this disparity may be repetitive sequences within the genome. While both males and females carry these repeat sequences, scientists have suspected that the large number of repeats on the Y chromosome may create a “toxic y effect” that shortens males’ lives. To test this idea, Bachtrog studied male fruit flies from the species Drosophila miranda, which have about twice as much repetitive DNA as females and a shorter lifespan. They showed that when the DNA is in its tightly packed form inside the cells of young male flies, the repeat sections are turned off. But as the flies age, the DNA assumes a looser form that can activate the repeat sections, resulting in toxic side effects.

The new study demonstrates that Y chromosomes that are rich in repeats are a genomic liability for males. The findings also support a more general link between repeat DNA and aging, which currently, is poorly understood. Previous studies in fruit flies have shown that when repeat sections become active, they impair memory, shorten the lifespan and cause DNA damage. This damage likely contributes to aging’s physiological effects, but more research will be needed to uncover the mechanisms underlying repeat DNA’s toxic effects.

A natural compound previously demonstrated to counteract aspects of aging and improve metabolic health in mice has clinically relevant effects in people, according to new research at Washington University School of Medicine in St. Louis.

A small clinical trial of postmenopausal women with prediabetes shows that the compound NMN (nicotinamide mononucleotide) improved the ability of insulin to increase glucose uptake in skeletal muscle, which often is abnormal in people with obesity, prediabetes or Type 2 diabetes. NMN also improved expression of genes that are involved in muscle structure and remodeling. However, the treatment did not lower blood glucose or blood pressure, improve blood lipid profile, increase insulin sensitivity in the liver, reduce fat in the liver or decrease circulating markers of inflammation as seen in mice.

The study, published online April 22 in the journal Science, is the first randomized clinical trial to look at the metabolic effects of NMN administration in people.

Our ultimate goal is to improve regeneration of functional skin—and maybe other organs with the a similar endogenous mechanism.

University of Manchester scientists have cast new light on how our skin repairs itself, bringing the possibility of regeneration of the organ a step closer.

The study team, funded by the Medical Research Council and Helmut Horten Foundation, showed the activation of specific parts of the DNA leading to better division of human skin cells. The study is published in Nucleic Acid Research.

Continue reading “Scientists cast new understanding of how skin repairs itself” »

From a serendipitous meeting of minds to laser-enabled precision, Cellino is leveraging AI and pluripotent stem cells for longevity.

Telomeres are large nucleoproteins structures that cap the ends of chromosomes in eukaryotic cells. When a cell divides, a small portion of the telomere is lost due to the inherently incomplete process of genome replication. If left unchecked, over time the telomeres will reach a critically short length and the cell will face genomic instability, deterioration or death. To offset this shortening, an essential enzyme called telomerase rebuilds the telomeres by synthesizing new telomeric DNA repeats at chromosome ends. Kelly Nguyen’s group, in the LMB’s Structural Studies Division, has solved the first complete atomic model of this enzyme and discovered a histone dimer as novel telomerase subunits.

Telomeres act as a barrier to protect the genetic information from progressive degradation arising from incomplete DNA replication. Additionally, telomeres distinguish the natural chromosome ends from DNA double-strand breaks, thereby avoiding an illicit DNA damage response and preventing intrachromosomal fusion. This makes telomeres essential for the preservation of genome and chromosome stability. In previous research, Kelly had discovered the architecture and composition of human telomerase holoenzyme at 8 Å (Ångströms) resolution using cryo-EM. However, to understand the molecular mechanism governing telomerase mediated telomere maintenance, a high-resolution structure of the complex was required.

To conduct this study, Kelly’s group, in collaboration with Kathleen Collins at the University of California, Berkeley, and Rhiju Das at Stanford University, prepared telomerase by extracting it from cultured human cells, before imaging using cryo-EM—resulting in the collection of almost 44000 images. This data was analyzed using RELION—a complex computer program developed at the LMB—in order to achieve the 3.4−3.8 Å structure of telomerase. From this Kelly and members of her group, George Ghanim, Adam Fountain, and Marike van Roon, were able to build the first complete atomic model of telomerase, with 12 protein subunits and telomerase RNA. By completing the structure to such a high resolution, the group was not only able to illuminate how common RNA and protein motifs work together, but also to highlight new interactions.

Any discussion of rejuvenation biotechnology almost certainly includes the subject of and the objection that medical advances that directly address the various processes of aging will lead to an overpopulated world. Such dire predictions are a common theme in many discussions involving advances in medicine that could increase human lifespans.

Overpopulation is a word that gives the simple fact of population growth a negative connotation. It implies that an increase in the number of people will harm our lives in different ways, such as famine, scarcity of resources, excessive population density, increased risks of infectious diseases, and harm to the environment.

Continue reading “Increased Longevity and Overpopulation” »

There are several key technologies converging on an inevitable effect, namely a dramatic, explosive increase in human population. Currently around 40% of Earth’s total land area is dedicated to agricultural production to feed seven billion people, but, interestingly, while the human population will increase, the land area required to sustain this population will decrease, approaching zero land area to sustain a trillion human lives. In this era, bulk elements such as gold will have no value, since they will be so easy to produce by fusion separation of elements from bulk rock. Instead, value will be attached to biological material and, most importantly, new technologies themselves.

The several key emerging technologies that make this state of affairs unstoppable are listed along with aspects of their impact:

1) Most important is fusion energy, an unlimited, scalable energy, with no special fuel required to sustain it. This will allow nearly all agriculture to be contained in underground “vertical farm” buildings, extending thousands of feet downwards. Cheap artificially-lighted, climate-controlled environments will allow the maximum efficiency for all food crops. Thus, agriculture will take up close to zero surface area, largely produced underground on Earth or the Moon.

Continue reading “Approaching a Singularity, When The Number of Humans Alive Will Equal The Number Who Have Ever Died” »

Rejuvenate Bio’s treatment is a gene therapy that dials up expression of the genes sTGFbetaR2 and FGF21 to reduce levels of the cytokine TGF-beta1 and boost levels of the hormone FGF21, respectively. Both genes are associated with longevity.

“What we have seen from using a combination of two genes is the ability to affect multiple age-related diseases at once,” Oliver said.

Rejuvenate Bio published data in November 2019 showing that targeting these two genes in mice reduced kidney atrophy and reversed weight gain and Type 2 diabetes. The company had given extra copies of those genes, alone and in combination with each other and another gene called alpha-Klotho to see if they could boost the mice’s health and life spans. It found out that more isn’t necessarily better, as mice that were given all three genes together fared worse than the other animals did.

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