Klotho Neuroscience Unveils Groundbreaking Approach to Extend Lifespan by Reactivating the Silenced Alpha-Klotho Gene

June 9, 2025

Pre-clinical research highlights the potential of alpha-Klotho gene expression to reverse age-related degeneration and increase both lifespan and health span

DENVER, Colo., Jun 09, 2025 (247marketnews.com)- Klotho Neuroscience (NASDAQ:KLTO) reported compelling findings from recent pre-clinical studies suggesting that reactivation and elevated expression of the alpha-Klotho (α-Klotho) gene may hold the key to extending human lifespan and reversing age-associated degeneration across multiple organ systems.

The company’s research is built upon the foundational discovery made by Professor Makoto Kuro-O in 1997, which revealed that lower levels of Klotho protein in the bloodstream are closely correlated with shorter lifespans in mammals. Further studies from Kuro-O’s lab demonstrated that genetic overexpression of full-length Klotho in mice increased average lifespan by 30–40%, sparking global interest in Klotho as a master regulator of aging.

Recent breakthroughs now focus on the secreted form of the Klotho protein (s-KL), which exerts powerful biological effects on pathways linked to metabolism, inflammation, and cellular repair. A 2025 study led by Joan Roig-Soriano et al., published in Molecular Therapy, demonstrated that administration of s-KL using an AAV9 gene therapy vector in both naturally aging and accelerated-aging mouse models led to significant improvements in physiological function and a 20% extension in lifespan.

Dr. Joseph Sinkule, Klotho’s CEO, said, “KLTO has secured an exclusive worldwide license for s-Kl from Universitat Autònoma de Barcelona (UAB) and Institució Catalana de Recerca i Estudis Avançats (ICREA) in Spain. As a result, we have the exclusive use of patents issued in the USA, Europe, and China covering a secreted splice variant of mammalian Klotho referred to as s-KL, as a treatment for neurodegenerative and age -related disorders. Professor Makoto Kuro-O is also a scientific advisor to KLTO. This recently published paper provides further credence to our development of s-KL as a treatment to reduce age-associated degeneration where, as a company, KLTO has a particular focus on neurodegenerative diseases such as ALS, Alzheimer’s and Parkinson’s disease. The results disclosed in the paper show the potential of elevating s-KL protein expression, resulting in the reduction of age-associated degeneration in multiple organs, increasing both life and health span.”

The company’s proprietary platform leverages adeno-associated virus serotype 9 (AAV9) to deliver the secreted Klotho gene isoform directly into the bloodstream, leading to sustained expression and elevated circulating s-KL levels. This delivery system is designed to target multiple tissues and activate protective pathways associated with cognitive health, skeletal integrity, and immune resilience.

Key Highlights:

  • ✅ 20% Increase in Lifespan observed in s-KL-treated mice
  • ✅ 30–40% Increase in lifespan observed with full-length Klotho gene overexpression (prior studies)
  • ✅ s-KL shown to mitigate markers of neuroinflammation, sarcopenia, and osteoporosis
  • ✅ Utilization of AAV9 vector ensures broad tissue distribution and efficient gene delivery

These findings position Klotho Neuroscience as a leader in the emerging field of longevity biotechnology, with a unique focus on restoring function through genetic activation of silenced anti-aging pathways. The company is now advancing its lead AAV9-Klotho gene therapy candidate toward clinical readiness.

 

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