Research shows tardigrade proteins can slow metabolism in human cells

Wyoming researchers spotlight tardigrade proteins as potential candidates in tech centered on slowing the aging process.

Water, an essential element for life, is conventionally deemed indispensable for all metabolic processes. However, certain organisms challenge this notion by surviving extreme dehydration, essentially losing all cellular hydration. These desiccation-tolerant organisms enter a state of biostasis known as anhydrobiosis, wherein they become ametabolic until rehydration triggers a resumption of normal metabolism and development. Among these remarkable organisms, tardigrades stand out, using intrinsically disordered proteins (IDPs) to endure desiccation, particularly Cytoplasmic Abundant Heat Soluble (CAHS) proteins.

Longevity.Technology: Tardigrades, also known as water bears, are microscopic creatures measuring less than half a millimeter long. They possess extraordinary survival abilities, capable of withstanding being completely dried out, frozen to just above absolute zero, heated to extreme temperatures, irradiated several thousand times beyond human tolerance, and even the vacuum of outer space. While these talents are all worthy of research, the fact that aging-related deterioration can be temporarily arrested or slowed down due to the process of anhydrobiosis [1] means that understanding the role CAHS proteins play could lead to the development of novel therapeutics.

CAHS proteins, which are a tardigrade-specific family of IDPs, exhibit gelation properties which are thought to contribute to their protective function. However, despite some quite intense research in this area, several important facets of their biology are still to be explained.

CAHS proteins have been shown to form gels both in vitro and in vivo, linked to their protective capacity. However, the sequence features and mechanisms underlying gel formation, and the necessity of gelation for protection, have not been fully elucidated.

University of Wyoming researchers have recently made significant strides in understanding tardigrade survival mechanisms and the role of CAHS proteins. Led by Senior Research Scientist Silvia Sanchez-Martinez in the lab of UW Department of Molecular Biology Assistant Professor Thomas Boothby, recent research sheds new light on tardigrade biostasis [2].

The researchers found that in vitro, gelation restricts molecular motion, immobilizing and protecting labile material from the harmful effects of drying. In vivo, they observed that CAHS D, a CAHS protein derived from the tardigrade Hypsibius exemplaris, forms fibrillar networks during osmotic stress, improving survival of osmotically shocked cells. Two emergent properties associated with fibrillization were observed: prevention of cell volume change and reduction of metabolic activity during osmotic shock. Importantly, CAHS D’s fibrillar network formation is reversible, and metabolic rates return to control levels after CAHS fibers are resolved. This work provides insights into how tardigrades induce reversible biostasis through the self-assembly of labile CAHS gels.

“Amazingly, when we introduce these proteins into human cells, they gel and slow down metabolism, just like in tardigrades,” lead author Silvia Sanchez-Martinez, a Senior Research Scientist in the lab of UW Department of Molecular Biology Assistant Professor Thomas Boothby explained. “Furthermore, just like tardigrades, when you put human cells that have these proteins into biostasis, they become more resistant to stresses, conferring some of the tardigrades’ abilities to the human cells.”

Importantly, the research shows that the whole process is reversible: “When the stress is relieved, the tardigrade gels dissolve, and the human cells return to their normal metabolism,” Assistant Professor Thomas Boothby said.

The research not only enhances our understanding of tardigrade biology but also provides avenues for pursuing technologies centered around inducing biostasis in cells and whole organisms to slow aging and enhance storage and stability. Moreover, the research offers insights into how CAHS proteins from tardigrades might be harnessed or engineered to stabilize sensitive pharmaceuticals, opening new avenues for medical applications.

The study, published in the journal Protein Science, marks a significant step forward in unlocking the potential of tardigrade proteins in various fields, from biotechnology to medicine. As research delves deeper into the mechanisms of tardigrade survival, innovative solutions for combating aging, enhancing medical treatments, and improving the storage and stability of vital biological materials may be uncovered.

[1] https://zslpublications.onlinelibrary.wiley.com/doi/epdf/10.1111/jzo.12677
[2] https://onlinelibrary.wiley.com/doi/10.1002/pro.4941