Throughout my years in aging research, I’ve observed numerous promising rejuvenation treatments rise and fall. The cycle began with resveratrol, hailed by Sartoris Pharmaceuticals as a potential anti-aging miracle. In 2008, GlaxoSmithKline acquired the company for $720 million, only to abandon it five years later when it failed to deliver results. Disappointments similar to this have occurred with caloric restriction and other promising approaches, including the aging master switch MTOR and senescent cell destruction, aimed at eliminating the aging-causing “zombie cells.”

So, when I learned about the first clinical trials of a new class of rejuvenating drugs, I tried to temper my excitement. But as I observed developments, I began to believe that perhaps this time could be different due to the concept of “partial reprogramming,” showing real promise.

The journey began in 2006 when Shinya Yamanaka presented a revolutionary paper at Kyoto University, detailing groundbreaking work conducted with his colleague Kazutoshi Takahashi. They discovered that by adding just four genes to mature skin cells, they could revert them to a fetal state, termed induced pluripotent stem cells (iPSCs). This breakthrough opened doors in biological sciences.

The therapeutic potential of iPSCs became quickly apparent. Numerous age-related diseases stem from damaged cells, which could theoretically be treated by creating iPSCs from a patient’s own cells. These reprogrammed cells could then be utilized to repair damaged organs—essentially providing rejuvenation. Additionally, iPSCs offer a way to source stem cells without the ethical dilemmas associated with cloning or embryo destruction.

However, the transition from lab discoveries to clinical applications would be long and arduous. Yamanaka’s research was primarily conducted on mice, posing uncertainties for human applications. Furthermore, while these cells mimic embryos, they fundamentally differ, and the efficiency of the process remained low—less than 1 in 1000 cells became pluripotent. Adding to the complexity, the use of retroviruses to deliver genes carried the risk of integrating into the host genome, potentially leading to cancer.

For many, these challenges obscured the therapeutic potential of iPSCs, despite their scientific validity, which ultimately warranted Yamanaka a Nobel Prize in 2012. In 2008, Tom Okama, president of the biotechnology company Geron, referred to them as “substitutes for nature” that would be impractical and prohibitively expensive for clinical use.

Yet, obstacles have been systematically addressed. Yamanaka confirmed this technique is viable in human cells, even without the c-Myc gene. Researchers have also developed alternative methods to bypass retroviral delivery, such as using adenoviruses. In 2016, the innovative concept of partial reprogramming emerged, enabling temporary activation of genes, allowing cells to rejuvenate while minimizing risks—successfully reversing this direction.

Returning to the current clinical trial, this marks the first human test of partial reprogramming. The focus is on glaucoma and non-arteritic anterior ischemic optic neuropathy (NAION), both age-related degenerative eye diseases.

A group of eighteen participants (12 with glaucoma and 6 with NAION) will receive a single intraocular injection of a non-infectious virus that includes Yamanaka factors, excluding c-Myc. Following the injection, patients will take oral medication for 56 days, activating the factors before deactivating them. This is a Phase I trial aimed at demonstrating safety. If successful, the trial will progress to Phase II to assess potential degeneration reversal. While it may take years to determine outcomes, the drug’s developer, Life Biosciences of Massachusetts, aims to explore treatments for numerous other age-related conditions.

Stay tuned—partial reprogramming could revolutionize rejuvenation therapies and fundamentally transform our approach to aging. As João Pedro de Magalhães at the Institute of Aging and Chronic Disease noted in 2019, “If even one company succeeds in slowing the aging process, it will have a monumental impact on medicine and society.”