This week on Lifespan News, Brent Nally talks about how the COVID-19 spike protein causes inflammation, a NASA challenge for engineering human tissue, and the complete sequencing of the human genome.
The spike protein that allows the SARS-CoV-2 virus to easily enter human cells might be responsible for an increase in the production of inflammatory cytokines by senescent cells. So, are there any treatments for this in humans? Vascularized human tissue has been created by two different teams at the Wake Forest Institute for Regenerative Medicine! This achievement earned them a prize that NASA and the Methuselah Foundation put up in 2016. And the human genome has finally been fully sequenced, telomere-to telomere! You’ll find these stories in this episode of Lifespan News.
Welcome to Lifespan News on X10, your source for longevity science updates. I’m your host, Brent Nally. We encourage you to check the description below for links to these stories.
For our first story, the COVID-19 spike protein is shown to increase the senescence-associated secretory phenotype, or SASP. New research published in the journal Science has shown that the infamous spike protein that allows the SARS-CoV-2 virus to enter human cells causes senescent cells to secrete more SASP. SASP is a mix of chemicals that is produced by senescent cells and is known to contribute to age-related chronic inflammation. We also discussed SASP in last week’s episode of Lifespan News. Previous studies had already found a correlation between the severity of COVID-19 and known factors of the SASP. Wanting to see if there was more to it than a mere correlation, the researchers ran a few different experiments involving lab mice and human cells. The first step for the scientists was to expose healthy human cells to the SASP. After exposure, kidney cells had two key viral defense genes suppressed—an effect that was partly reversed upon administration of antibodies against some of the SASP factors. Other SASP-exposed cells showed greater expressions of genes that are critical to SARS-CoV-2’s entry into the cells or anyway facilitate the infection. The scientists then sought to assess the effects of pathogen exposure on senescent cells. To that end, the scientists exposed lab mice to pet store mice, which unlike the former, generally carry many common murine diseases. Of the exposed mice, 89% of young ones survived, but 100% of 20-month-old mice (which is quite old, for mice) died within two weeks of exposure. The scientists’ analyses revealed that SASP factors were significantly increased in older exposed mice compared to younger ones, which backs up the researchers’ hypothesis that pathogen exposure makes senescent cells go hyperactive. According to the data, a particular type of coronavirus, mouse hepatitis virus, or MHV, was largely responsible for the high mortality observed in older mice. Immunizing old mice against MHV protected them against death due to microbe exposure. Further, the scientists tried to see whether reducing the senescent cell burden of older mice would protect them against the lethal effects of MHV. To do that, the scientists administered 20-month-old mice with fisetin, a well-known compound able to clear senescent cells. As a result, half of the mice survived MHV, whereas all the controls that did not receive fisetin died. Similar results were obtained with different senolytic compounds, such as dasatinib and quercetin. The researchers concluded that removal of senescent cells through senolytics might therefore be a possible approach to reduce the effects of coronavirus infection in humans, though this remains to be seen. Future human trials of senolytics may shed some light on that question.
For our next story, scientists engineered complex human tissues and won top prizes in a NASA challenge. Scientists from the Wake Forest Institute for Regenerative Medicine in North Carolina have won the vascular tissue challenge that NASA threw all the way back in 2016. The Vascular Tissue Challenge was launched in cooperation with the Methuselah Foundation, a well-known charity in the longevity space with a goal to accelerate regenerative medicine progress to make “90 the new 50 by 2030”. The Methuselah Foundation received a generous multi-million dollar cryptocurrency donation from Vitalkin Buterin a few weeks ago which we reported on Lifespan News. Using different 3D-printing techniques, the first- and second-place teams managed to engineer lab-grown human liver tissues that were able to survive and function similarly to authentic tissue. The small cube of tissue they created functioned for 30 days in the lab. The potential applications of this technology range from research to therapeutic: they could accelerate drug testing, disease modeling, and over the longer haul, may lead to custom-created replacement organs for patients in need, thereby helping to end organ shortage. The true challenge of creating replacement tissue for human organs is that real tissue is vascularized — that is, it contains blood vessels, which are needed to supply the tissue cells with nutrients, oxygen, and remove metabolic waste. Recreating a similar network in engineered tissue is anything but easy, and it’s the reason why the challenge was thrown in the first place. The 3D-printing technologies employed by the two winning teams allowed them to create gel-like scaffolds with a network of channels that, much like blood vessels, allowed the engineered tissue to survive in the lab for 30 days, as required by the challenge terms. Besides medical applications here on Earth, the technology has applications in space, too: this type of tissue could be used to study the effects of radiation exposure or organ function in microgravity conditions, which is one of the reasons why NASA was interested. The competition was executed by New Organ Alliance, an initiative by the aforementioned Methuselah Foundation. The prize money was provided by the Methuselah Foundation and NASA’s Centennial Challenges. Our congratulations to the winning teams, and huge thanks for their contribution to bringing healthy longevity a step closer to reality.
As we’ve shared over the last month on Lifespan News, Lifespan.io launched a crowdfunding campaign on May 17th, 2021 to support longevity research by funding a large human trial called the Participatory Evaluation of Aging with Rapamycin for Longevity Study, or PEARL. A huge thanks to everyone who donated to help us achieve our stretch goal of $160,000 USD. We’re currently at about $166,000 USD. Funding ends June 17th, 2021. Check the link in the description below to learn more about PEARL and make a donation.
For our final story, the human genome has finally been fully sequenced for the first time, telomere-to-telomere, more than two decades after the first draft of its sequencing. The previous project left gaps that have been filled by new sequencing technologies. The human genome was first sequenced about 20 years ago. This draft included roughly 90% of the genome, which took scientists about ten years to achieve. The task was declared completed three years later, in 2003, but almost 8% of the genome remained undeciphered because of technical constraints. Regions with multiple tandem repeats, such as centrosomes and telomeres, were too difficult to properly assemble with the sequencing approaches available. With the advent of sequencing technologies using longer read lengths, that technical hurdle has been overcome. Researchers used sequencers from PacBio and Oxford Nanopore to complete the missing segments. This added almost 200 million base pairs of novel sequences that contain more than 2,000 paralogous gene copies. 115 of the newly found genes are predicted to code for proteins – which is a small but considerable portion – and many more probably code for RNA that is not translated into proteins but is still used in gene regulation in what is known as RNA interference. Now that the gaps in the genome have been filled, the next challenge is to capture a more diverse snapshot. The current reference was assembled from the genes of 13 anonymous volunteers, and most of the sequencing data that has been accumulated is from people of European descent. Building reference genomes from other populations to capture the complexity and diversity of our genetic endowment is vital to get an accurate picture of genomic variation and its consequences.
That’s all the news for this episode. Lifespan News now has a couple new stories every week on X10’s parent YouTube channel, Lifespan.io, so make sure you’re subscribed so you don’t miss any videos. Is there a recent life extension story that you think we should have covered but haven’t yet? And what was your favorite story from this episode? Let us know what you think in the comments below and we’ll see ya in the next episode.