During Elon Musk’s visit to Davos last week, an interviewer inquired whether he believed aging could be reversed. Musk indicated that he hasn’t devoted much time to the issue but believes it is “highly solvable” and that when researchers uncover the reasons behind aging, it will likely be something “apparent.”
Shortly thereafter, Harvard professor and longevity advocate David Sinclair joined the discussion on X to strongly concur with the world’s wealthiest individual. “Aging has a comparatively straightforward explanation and is seemingly reversible,” Sinclair stated. “Clinical Trials will commence soon.”
“ER-100?” Musk queried.
“Yes,” Sinclair responded.
ER-100 is revealed to be the codename of a therapy developed by Life Biosciences, a modest Boston startup that Sinclair co-founded and which he confirmed today has received FDA authorization to move forward with the first targeted effort at age reversal in human subjects.
The organization intends to treat eye ailments using a groundbreaking rejuvenation method known as “reprogramming” that has recently garnered substantial investments from Silicon Valley companies like Altos Labs, New Limit, and Retro Biosciences, supported by numerous leading figures in technology.
This technique aims to restore cells to a more optimal condition by generally resetting their epigenetic controls—switches on our genes that dictate which ones are activated and inactivated.
“Reprogramming resembles the AI of the biological realm. It’s the focus of considerable funding,” remarks Karl Pfleger, an investor supporting a smaller UK startup, Shift Bioscience. He notes that Sinclair’s firm has been actively seeking more funds to continue advancing its treatment.
Reprogramming is so potent that it can sometimes introduce risks, even leading to cancer in laboratory animals, but the iteration of the technique being pursued by Life Biosciences has cleared initial safety assessments in animals.
Nevertheless, it remains highly intricate. The initial trial will focus on approximately a dozen patients suffering from glaucoma, a condition marked by increased pressure within the eye that harms the optic nerve. In these trials, viruses carrying three powerful reprogramming genes will be injected into one eye of each participant, as per a study description first released in December.
To prevent the process from going overboard, the reprogramming genes will operate under a unique genetic switch that activates them only while the patients are on a low dosage of the antibiotic doxycycline. They will initially take the antibiotic for about two months while monitoring the effects.
The company’s executives have indicated for months that a trial could commence this year, occasionally framing it as the starting signal for a new chapter in age reversal. “It’s an incredibly significant development for us as a field,” Michael Ringel, chief operating officer at Life Biosciences, stated at an event this autumn. “This will mark the first instance in human history, throughout millennia, of seeking something that rejuvenates … So stay tuned.”
The technology is founded on the Nobel Prize-winning discovery made 20 years ago that introducing a few powerful genes into a cell can revert it back into a stem cell, similar to those found in early embryos that develop into various specialized cell types. These genes, referred to as Yamanaka factors, have been compared to a “factory reset” button for cells.
However, they are also hazardous. When activated in a living organism, they can lead to a surge of tumors.
This led scientists to a novel concept called “partial” or “transient” reprogramming. The aim is to limit the exposure to the potent genes—or use only a selection of them—hoping to make cells behave younger without erasing their memory of their roles in the body.
In 2020, Sinclair asserted that such partial reprogramming could restore vision in mice after their optic nerves were damaged, claiming there was even evidence of nerve regrowth. His findings featured on the cover of the prestigious journal Nature with the headline “Turning Back Time.”
Not all scientists believe that reprogramming genuinely constitutes age reversal. Nonetheless, Sinclair has reaffirmed his stance. He has been promoting the idea that the gradual depletion of accurate epigenetic information in our cells is, in actuality, the primary cause of aging—precisely the kind of root cause Musk referenced.
“Elon does seem to be keeping an eye on the field and [is] apparently aligned with [my theory],” Sinclair mentioned in an email.
Reprogramming is not the first longevity solution advocated by Sinclair, who has authored popular books and commands high fees on the longevity lecture circuit. Previously, he praised the longevity advantages of molecules known as sirtuins and resveratrol, a compound found in red wine. However, some critics argue he significantly inflates scientific advancements, a backlash that culminated in a 2024 Wall Street Journal article that labeled him a “reverse-aging guru” whose ventures “have not materialized.”
Life Biosciences has been among the companies facing struggles. Established in 2017, it initially aimed to launch subsidiaries, each targeting a specific aspect of the aging dilemma. However, after making limited headway, in 2021 it appointed a new CEO, Jerry McLaughlin, who has redirected focus towards Sinclair’s mouse vision findings and the movement towards a human trial.
The company has explored the possibility of reprogramming other organs, including the brain. Additionally, Ringel, like Sinclair, entertains the notion that total body rejuvenation could one day be achievable. However, for the moment, it’s more prudent to view the study as a proof of concept that remains distant from a magical cure for youth. “The optimistic scenario is this could address some blindness for particular individuals and stimulate efforts for other applications,” comments Pfleger, the investor. “It’s not as though your physician will prescribe a pill that revitalizes you.”
Life’s treatment also relies on an antibiotic switching mechanism that, while commonly used in laboratory animals, has not been tested on humans previously. Since the switch employs genetic elements derived from E. coli and the herpes virus, it’s conceivable that it might provoke an immune reaction in humans, scientists caution.
“I’ve always considered that for widespread application, you might require an alternative system,” states Noah Davidsohn, who assisted Sinclair in implementing the technique and now serves as chief scientist at another company, Rejuvenate Bio. Life’s selection of reprogramming factors—it’s chosen three, abbreviated as OSK—may also introduce risks. These are forecasted to activate hundreds of other genes, and in certain instances, the combination could prompt cells to revert to a highly primitive, stem-cell-like condition.
Other companies investigating reprogramming assert their attention is centered on identifying the optimal genes to utilize, aiming for time reversal without undesirable side effects. New Limit, which has been extensively searching for such genes, states it will not be prepared for a human trial for another two years. At Shift, animal experiments are just commencing now.
“Are their factors the optimal solution for rejuvenation? We don’t believe they are. I think they’re working with what they have,” comments Daniel Ives, the CEO of Shift, regarding Life Biosciences. “But I believe they are significantly ahead of anyone else in progressing to human trials. They have identified a strategy to move forward in the eye, which is a neat, self-contained system. If it does not succeed, there’s still one left.”
