Water-Bear ‘Biostasis’ Mechanism May Hold Key to Enhancing Human Longevity

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

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.

“Slight differences in capsid proteins can modulate the efficiency with which different capsids deliver genes to different cells, thus allowing different AAV capsids to be selected to most effectively target particular 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.