Biotech
Water-Bear ‘Biostasis’ Mechanism May Hold Key to Enhancing Human Longevity
Securities.io is not an investment adviser, and this does not constitute investment advice, financial advice, or trading advice. Securities.io does not recommend that any security should be bought, sold, or held by you. Conduct your own due diligence and consult a financial adviser before making any investment decisions.
Biostasis and The Unkillable Water Bears
When studying biology and medicine, researchers have always been interested in discovering what seems to be “missing” in other species in humans. This has so far included, for example, sharks' resistance to cancer, immortal jellyfish, the longevity-enhancing effect of caloric restrictions on mice and monkeys, and reptiles' regeneration abilities.
Another animal that has intrigued researchers for decades is the “water bear,” “moss-piglets,” or tardigrade. This is a group of 1,100 species close to arthropods (insects, crustaceans). They are very small, less than 1mm / 0.04 inches in size, and live in water-rich environments in sand, mosses, flowering plants, and fresh and saltwater.
Source: Britannica
What makes the tardigrades special is their extreme resistance to extreme environmental conditions. They can put themselves in a state of biostasis, or “tun” state, where their metabolism is only 0.01% of what it is in normal conditions.
This ability to enter biostasis gives tardigrades extreme resistance to desiccation, allowing them to wait years and eventually decades until water comes back.
They have also been shown to survive a vacuum for 8 days and 3 days in an oxygen-free helium atmosphere. Specimens have also survived temperatures as low as −272 °C / −458 °F for several hours, as low as −190 °C / −310 °F (liquid air) for 21 months, and as high as 148 °C / 300 °F.
So, it is no surprise that if even a fraction of this extraordinary resilience through biostasis could be applied to humans, it could radically change human health and maybe longevity.
Biostasis Proteins
Researchers Silvia Sanchez-Martinez and Thomas Boothby at the University of Wyoming have discovered that tardigrades' resilience might be driven by specific proteins called CAHS (Cytoplasmic Abundant Heat Soluble).
In a recently published paper titled “Labile assembly of a tardigrade protein induces biostasis,” they have shown that these newly identified proteins cause the metabolisms to slow down, helping the tardigrades' weather conditions too harsh to survive without biostasis.
This discovery builds upon previous research done by the same scientists, showing that tardigrade proteins could be used to stabilize and preserve the pharmaceutical product human blood clotting Factor VIII at room temperature. This is normally a very fragile molecule that degrades whenever it is not in a precise temperature range.
Understanding Biostasis Proteins
The research investigated a few things about these proteins. First, it tried to understand the protein sequence responsible for its protective effects. Second, it tried to understand how they perform their function.
They discovered that CAHS proteins can form a gel-like structure. When diluted again, this gel can return to a liquid state. This is most likely the main mechanism activating CAHS proteins in the case of desiccation, the main threat to tardigrades in nature.
They also found that the CAHS proteins have a “dumbbell” 3d configuration, and were composed of mostly 3 parts.
Source: Protein Science
The gel-forming capabilities are mostly linked to β sheet with β-sheet 3D structures interactions, leading to complex, tube-like structures to form.
Source: Protein Science
Overall, the gel formed by tardigrades' CAHS proteins slows down the cell's metabolism from the inside. They also demonstrated that this metabolism slow down, and no other effect, is responsible for the increased survival rate.
Source: Protein Science
Applying Tardigrades Resilience through Biostasis To Humans
CAHS Proteins In Human Cells
The researchers also genetically engineered human cells grown in the lab to produce a CAHS protein. These cells demonstrated an increased survival rate when facing osmotic stress.
Source: Protein Science
They even proved that the same β-sheet interactions and gel-forming properties important in tardigrades' survival were also responsible for the increased resistance of modified human cells.
Lastly, they have shown that the biostatis induced by tardigrades protein in human cells was also reversible in humans.
Anti-Aging Applications
Aging is often correlated to metabolic activities and oxidation. Especially when combined with cellular stress induced by chemicals, pollutants, or overall poor environmental conditions.
This is considered one of the major reasons why reducing calorie intake tends to increase the longevity of many organisms.
As it seems that CAHS proteins can reduce metabolism in case of stress, it could also be helping to reduce one of the major causes of aging.
Biotech Applications
Medicine
Another potential application of tardigrades’ CAHS proteins is in the preservation of pharmaceutical biomolecules and stored cells. What was previously done for blood clotting Factor VIII could potentially be applied to medical treatments as diverse as mRNA vaccines, stem cells, hormones, drugs, etc.
Potentially, even food could benefit from these proteins being used to increase their shelf life without freezing or refrigeration altogether.
Farming
Because NAHS proteins provide strong protection against desiccation, they could also be used to improve crops' resistance against drought. The extra resistance to extreme temperatures might also apply to plants to some extent. With climate change increasingly impacting farming, this could be a strong new segment of possible application for tardigrade proteins.
Anti-Aging & Longevity Companies
1. MeiraGTx Holdings
MeiraGTx is a gene therapy company with a focus on aging and using the adeno-associated virus (AAV) as the vector for delivering genes. The focus on AAV allows the company to develop very customizable therapies for different pathologies and cell types.
The technology also comes with an on/off “riboswitch” that activates the gene added to the patient's body on demand, giving an extremely high level of control over the gene therapy.
The company is active in 3 therapeutic fields: ocular, neurodegenerative (including Parkison’s disease), and salivary gland diseases.
In December 2023, MeiraGTx entered into a $415M asset purchase agreement with Janssen for its X-linked retinitis pigmentosa (XLRP) treatment. The company also has 2 other ongoing ocular clinical trials in partnership with Janssen.
Source: MeiraGTX
The extreme level of control over the activation of the gene therapy of MeiraGTx technology could be highly relevant for future longevity therapy.
It could help reduce the risks of unwanted side effects often hindering the prospects of anti-aging therapies. If applying tardigrades' CAHS protein to human cells, it could make them expressed “on-demand” in specific tissues or respond to specific conditions, reducing medical and regulatory risks.
2. Lineage Cell Therapeutics
Lineage is producing 200+ different human cell types for implantation, starting with pluripotent cells and using a proprietary guided differentiation method.
Lineage has 2 potential products well advanced in phase 2 of clinical trials, and 3 other at an earlier stage.
Source: Lineage
The flagship product is OpRegen, in partnership with Genentech, which treats eye problems, including age-related macular degeneration (AMD). Lineage received from Genentech $50M up front and is eligible for $620M of milestone payments and double-digit royalties. The initial trial achieved unprecedented retinal regeneration for 5/12 patients.
The second more advanced program is OPC1 (Oligodendrocyte Cell Transplants) for spinal cord injury. The treatment could help protect the spinal cord and dramatically reduce the number of patients showing no improvement. The initial results have been encouraging, with many patients regaining sensations they would likely not have without the treatment.
Source: Lineage
“I couldn’t drink, couldn’t feed myself, couldn’t text or pretty much do anything, I was basically just existing. I wasn’t living my life, I was existing.” – Kris Boesen, OPC1 Patient
If cells with CAHS proteins are indeed more resilient (even without reaching tardigrade levels of resistance), it could be a new venue for developing new anti-aging solutions and add to the 200+ human cell line already in the catalog of Lineage Cell Therapeutics.
3. Bayer Crop Sciences
Bayer Crop Sciences, making up half of the group together with the pharmaceutical segment, focuses on innovations around seeds and traits and crop protection.
Source: Bayer
The company is partially a crop protection company, with a solution spectrum including herbicides, fungicides, and insecticides. The crop protection mechanism safeguards around 30 percent of yields worldwide, equivalent to 550 million tonnes of food that could feed more than 2 billion people.
It is also a very innovative company, with projects in virtually every possible way to improve plants and crops.
Its innovations have helped its biotechnology scientists to make targeted improvements within plant DNA. Its solutions help control weeds through built-in herbicide tolerance and help farmers preserve the genetic potential of their seed while growing more efficiently with substantially reduced environmental impact.
Drought-related losses in farming represented a cumulated loss of $166B between 1983-2009. And forecasts warn that climate change might increase this problem.
So if it turns out that CAHS proteins from tardigrades can reduce osmotic stress not only in animal but also plant cells, this could be an interesting venue for companies like Bayer to create drought-resistant crops through genetic engineering, adding to their existing roster of GM plants and gene editing R&D efforts.
