α-Klotho - the "Longevity Protein"

Longevity and Quality of Life

α-Klotho’s wide-ranging protective effects make it a promising target for treating age-related diseases and developing anti-aging therapies. Research is advancing drug development, gene therapy, and methods to increase α-Klotho levels to reduce health risks in aging populations and transform treatments for conditions like heart disease, cancer, and neurodegeneration. Leveraging α-Klotho could extend healthy lifespans and enhance everyone's quality of life.

Discovering Klotho

α-Klotho Decreases with Age

Deficiency in α-Klotho accelerates age-related decline, leading to conditions like vascular calcification, osteoporosis, chronic kidney disease, cardiovascular issues, and cognitive impairment, with circulating levels naturally decreasing in humans as they age.

Conversely, overexpression of α-Klotho in animal models extends lifespan, enhances cognition, and protects against cardiometabolic diseases, highlighting its role as an “aging-suppressor” gene. Higher levels are associated with a reduced risk of age-related diseases and a 30% increased lifespan.

Replenishing α-Klotho Levels

Klotho, discovered in 1997 through mouse studies on accelerated aging, is a vital anti-aging protein primarily found in the kidney, brain, and parathyroid gland, existing in membrane-bound, soluble, and intracellular forms with diverse biological roles.

Avaí and Austrianova's Approach

Because α-Klotho plays a crucial role in aging and longevity, our therapy utilizes microencapsulated cells that have been genetically modified to continuously produce the α-Klotho protein, which is then released into the bloodstream, potentially restoring youthful levels, promoting health and extending lifespan. By encapsulating our therapies, we provide a body armor for the living cells, which protects, shields and extends the life of the α-Klotho producing cells inside.

α-Klotho Levels Decline with Age

α-Klotho naturally decreases as we grow older

Research shows a clear trend. Humans produce their highest levels of the α-Klotho protein early in life. As the decades pass, α-Klotho steadily declines. Lower α-Klotho is strongly associated with the onset of many age-related conditions.

What researchers have observed:
• Children and high-performance athletes show the highest α-Klotho levels
• α-Klotho begins to drop after age 30
• Lower α-Klotho levels correlate with a greater risk of age-related diseases including heart, kidney, lung, metabolic, neurodegenerative, and cancer-related conditions

Maintaining healthy α-Klotho levels may be essential to protecting resilience with age.

Demonstration of Klotho protein levels declining with age

α-Klotho Overexpression Improves Healthspan in Animals

Higher α-Klotho levels support resilience and improve survival in aging

In multiple independent studies, mice engineered to produce more α-Klotho lived significantly longer than normal mice. They also showed improved health outcomes as they aged.

Key findings from landmark studies:
• α-Klotho-overexpressing mice lived up to ~30% longer than wild-type controls
• α-Klotho-deficient mice developed rapid, premature aging and survived only a small fraction of a normal lifespan
• Results demonstrate α-Klotho’s role as a master regulator of aging biology

Increasing α-Klotho levels improved health and extended survival without other interventions.

Survival curves for mice with Klotho overexpression (example)
Studies: Kurosu et al., Science (2005); Kuro-o et al., Nature (1997)

Human α-Klotho Levels and Longevity

High α-Klotho protects long-term health and supports healthy aging

Human population data reveal that individuals with higher circulating α-Klotho levels are more likely to live longer, healthier lives. Those with low α-Klotho experience a noticeable increase in age-related mortality risk.

Key insights from a study of 10,069 U.S. adults (ages 40–79):
• Participants with low α-Klotho (<666 pg/mL) had a 31% higher risk of death over the study period¹
• Individuals with higher α-Klotho showed the greatest long-term survival¹
• Findings support α-Klotho as an important biomarker of healthy aging

📚 Reference
¹ Kresovich JK, Bulka CM. Low Serum Klotho Associated With All-Cause Mortality Among a Nationally Representative Sample of American Adults. (PubMed ID: 34628493)

Survival curve demonstrating the relationship between human Klotho levels and mortality risk

Live Cell Encapsulation

Klothonova’s Unique Cell Protection Strategy

Unique delivery technology: Utilizes Austrianova’s clinically proven microencapsulation protection technology (Cell-in-a-Box®) to protect and deliver α-Klotho-producing cells.

Microencapsulation protects the α-Klotho-producing cells from immune rejection and allows for sustained protein production over months and years, enhancing therapeutic benefits.

What advantages does microencapsulation offer?

Combining a α-Klotho Expressing Cell Line with Cell-in-a-Box® Encapsulation Technology: Continuous Production of α-Klotho to Avoid Short Half-Life Issues

Preclinical data shows high level of secreted α-Klotho from encapsulated cells.

An example of a α-Klotho producing cell line, combined with Austrianova’s micro-cell encapsulation, yielded:

• ~580pg Klotho protein/ 1000 cells /24 hrs

• ~8120pg Klotho protein/ capsule/24 hrs

In cell culture, α-Klotho producing cell lines can be encapsulated and have around 14,000 cells/capsule.

1.5 mls of medium or 150 capsules required to “boost” α-Klotho levels in humans.

Encapsulated α-Klotho producing cells produce ~580pg Klotho/1000 cells.