LongeCityNews Last Updated: 06 February 2026 - 09:29 PM

Life Biosciences has announced that its trial of cellular reprogramming aimed at two age-related vision diseases has received a go-ahead from the FDA. We spoke with the company’s CSO to get more details.

Life Biosciences, the biotech company based on Harvard professor David Sinclair’s research into cellular reprogramming, stunned everyone last year by announcing that its clinical trial, the first-ever human trial of a reprogramming technology, will commence in the first quarter of 2026. A few days ago, the company cleared the last major hurdle on its way to this ambitious goal by receiving an Investigational New Drug (IND) clearance from the FDA to test the experimental drug ER-100 against optic neuropathies.

ER-100’s story begins with highly successful experiments in rodents, where Sinclair’s team used their own partial cellular reprogramming recipe to restore vision after a severe optic nerve injury, and then proceeded to a successful trial in non-human primates. This upcoming trial is focused on open-angle glaucoma (OAG) and non-arteritic anterior ischemic optic neuropathy (NAION), which is a “stroke of the eye” that can cause sudden blindness. Both diseases are age-related, with NAION being the most common acute optic neuropathy in adults over fifty.

Life Biosciences uses a proprietary reprogramming cocktail based on three out of four of the original Yamanaka factors: OCT-4, SOX-2, and KLF-4 (OSK). The company believes that this approach solves several problems that plagued early reprogramming research.

“It’s incredibly meaningful to see this science reach clinical testing after more than 30 years of work,” Sinclair said to Lifespan News. “I’m grateful to the many students, collaborators, and partners whose dedication helped bring these ideas from the lab to this milestone. For me personally, it’s deeply rewarding to see this work move into the clinic, with the potential to protect and restore vision for patients and to help unlock a new generation of therapies that target the diseases of aging across tissues.”

As this is the first reprogramming clinical trial, and one of the first longevity therapy clinical trials, many people in this industry view it as a seismic event. “This is a huge milestone for the entire partial reprogramming field, and it aligns with what we’ve seen as well: the FDA has been notably open and forward-thinking in how it engages with this approach,” said Yuri Deigin, CEO of YouthBio, which is developing its own anti-Alzheimer’s reprogramming-based therapy. “It’s also a strong signal for the broader longevity space that regulators are increasingly willing to evaluate therapies that aim to modify upstream epigenetic drivers of aging, rather than only treating downstream symptoms.”

We have long followed Life Biosciences and interviewed both David Sinclair and Life CSO Sharon Rosenzweig-Lipson. Following the FDA clearance announcement, we spoke with Sharon again to get her perspective on the trial timeline, Life Biosciences’ experience of interacting with the FDA, and the company’s future trajectory.

When are you planning to start the actual trial, and when can we expect results?

We’re in the final stages of getting our first site activated. We expect that to happen within a few weeks and to start enrolling patients right after that. By March, we’ll have begun enrolling patients.

And the ETA on results?

Because it’s a gene therapy, we’re going to enroll patient number one, wait 28 days, then enroll patients two and three, wait another 28 days. Then we’ll make decisions about going up and down on the dose. It’s going to take time to get through that, but we hope to have enough information by the end of the year on one or more doses. This will allow us to make decisions about whether we go to Phase 2 and start planning the next stage. We’re as eager as everybody else to move this as quickly as possible.

Usually, partial reprogramming involves pulsing with very carefully calculated doses so that the cells don’t undergo dedifferentiation. I understand that your therapy is “one-shot” – based on a single round of continuous administration.

I want to separate what we call partial reprogramming from what others do, which is transient reprogramming. Sometimes, you see transient reprogramming where you give it one or two days, wait a few more days in animals, then give it one or two more days. That’s often done with all four factors.

That’s not what we’re doing. We’re going to give doxycycline systemically – it’s an inducible system – keeping OSK on for an eight-week period. We have data showing that we can do it not just for two months, but for three months, or even beyond that in mice, demonstrating that we can achieve good reprogramming and good safety with a more continuous expression system.

Do you see at least some shift toward dedifferentiation with more time on the therapy?

We do not. What’s amazing about using OSK is that it’s not causing de-differentiation. It’s resetting the epigenetic code. That code, which made normal hearts, lungs, livers, retinal ganglion cells, gets degraded as we age or with age-related diseases. Our therapy resets that code back to a healthy, youthful state, but not all the way back, not to pluripotency. Cell identity is maintained.

It looks like you cracked one of the hardest problems in partial reprogramming by taking out the M out of the original four-factor Yamanaka cocktail.

Exactly. Taking the M out makes it impossible to go all the way back. You just can’t push the system hard enough.

What can you tell me about your interactions with the FDA? Was there something that pleasantly surprised you?

We met with the FDA almost two years ago to plan for our tox studies and make sure that they bought into what we were doing in a way that we could move it forward. We went through a series of questions and together with our recommendations and their recommendations, we outlined a path for our toxicology studies, distribution studies, and what they wanted to see us do clinically. We were very conscious of all the FDA guidance. Overall, we had a very smooth interaction with the FDA as it related to our IND clearance.

Since it’s the very first human trial of cellular reprogramming, you would think they would be extremely cautious to the point of seriously slowing you down, but you’re saying it was smooth sailing?

Our experience was very collaborative and positive. We have a lot of data that we walked into the room with supporting the safety profile. We had data in mice, data in non-human primates. We had our IND studies. We walked in with a lot of safety data, and I think that really helped.

Do you think this signals a broader change in the FDA’s attitude toward longevity therapies in general?

It’s hard for me to say. It’s a one-off, right? We haven’t put seven things through the FDA, so it’s hard to get a bigger picture of what this means for them. We’re pleased that for what we did, it was positively perceived and most importantly, we got to our “may proceed” letter without any major issues.

If we look past the indications you’re currently working with, what’s next for Life Biosciences?

We’ve already talked publicly about having nice data on reprogramming in the liver, which is quite exciting. We’re continuing to work on the liver, and you may see in the next few months a little more information on some other indications we’re working on. We’re excited that we’re continuing to achieve proof of concepts across a range of indications.

This is an example of the very earliest stages of research leading to drug discovery, the identification of a potential target protein, here CUL5, that can be manipulated to change cell metabolism in a specific way, here meaning a reduction in the amount of tau protein in the cell. Aggregation of altered tau is a feature of late stage Alzheimer's disease, a cause of cell dysfunction and death in the brain. Reducing tau levels is one possible approach to the problem, though given that tau has a normal and necessary function in the brain, it may not be the best possible approach. At this stage, researchers do not know how CUL5 functions to affect tau levels, and thus a good deal of further work stands between the present discovery and the emergence of any practical outcome.

Aggregation of the protein tau defines tauopathies, the most common age-related neurodegenerative diseases, which include Alzheimer's disease and frontotemporal dementia. Specific neuronal subtypes are selectively vulnerable to tau aggregation, dysfunction, and death. However, molecular mechanisms underlying cell-type-selective vulnerability are unknown. To systematically uncover the cellular factors controlling the accumulation of tau aggregates in human neurons, we conducted a genome-wide CRISPR interference screen in induced pluripotent stem cell (iPSC)-derived neurons.

In comparison to other tau screens previously reported in the literature, our data have broadly similar patterns of hit genes. A previous genome-wide screen for modifiers of tau levels performed in SHY5Y cells has several shared classes of genetic modifiers. Surprisingly, this screen identified CUL5 as a negative modifier of tau levels. Since CUL5 regulates hundreds of substrates, it is not surprising that CUL5 knockdown has different phenotypes in different contexts.

We find CUL5 expression to be correlated with resilience in tauopathies along with genes encoding CUL5 interactors, including ARIH2 and SOCS4. However, the molecular mechanisms by which CUL5 affects neuronal vulnerability in AD remains to be identified. A broad distribution of CUL5 expression is seen in different neuronal subtypes in the Seattle Alzheimer's Disease Brain Cell Atlas suggesting that CUL5 may modulate disease vulnerability via multiple mechanisms. For instance, it is possible that CUL5 expression affects vulnerability via tau ubiquitination. But, considering CUL5's known role in immune signaling, another possibility is that CUL5 expression affects vulnerability via the neuro-immune axis.

Link: https://doi.org/10.1016/j.cell.2025.12.038

Parkinson's disease is driven by the spread of misfolded α-synuclein through the brain. The most evident symptoms result from the death and dysfunction of motor neurons, caused by the presence of misfolded α-synuclein. Once α-synuclein misfolds, it is capable of inducing other molecules of α-synuclein to misfold in the same way, and this dysfunction can slowly spread from cell to cell. In recent years, researchers have shown that in a sizable fraction of Parkinson's disease cases misfolded α-synuclein first emerges in the intestines and then spreads to the brain. Here, researchers uncover more of the mechanisms by which this transmission takes place, with an eye to finding ways to intervene in the earliest stages of the condition in order to prevent later consequences.

Emerging evidence suggests that Parkinson's disease (PD) may have its origin in the enteric nervous system (ENS), from where α-synuclein (αS) pathology spreads to the brain. Decades before the onset of motor symptoms, patients with PD suffer from constipation and present with circulating T cells responsive to αS, suggesting that peripheral immune responses initiated in the ENS may be involved in the early stages of PD. However, cellular mechanisms that trigger αS pathology in the ENS and its spread along the gut-brain axis remain elusive.

Here we demonstrate that muscularis macrophages (ME-Macs), housekeepers of ENS integrity and intestinal homeostasis, modulate αS pathology and neurodegeneration in models of PD. ME-Macs contain misfolded αS, adopt a signature reflecting endolysosomal dysfunction and modulate the expansion of T cells that travel from the ENS to the brain through the dura mater as αS pathology progresses. Directed ME-Mac depletion leads to reduced αS pathology in the ENS and central nervous system, prevents T cell expansion and mitigates neurodegeneration and motor dysfunction, suggesting a role for ME-Macs as early cellular initiators of αS pathology along the gut-brain axis. Understanding these mechanisms could pave the way for early-stage biomarkers in PD.

Link: https://doi.org/10.1038/s41586-025-09984-y

Aging research is not a field marked by its unity. At the high level there is some degree of consensus on the need to treat aging as a medical condition, and that this is a plausible goal given time and effort. But ask questions about any particular detail regarding the mechanisms of aging, how to progress towards therapies, the bounds of the possible, and the state of the field, and you will usually find almost as many opinions as there are researchers to hold them. This is characteristic of a field of study in which far more remains to be discovered than has been mapped to date. The research community cannot be said to fully understand the cell, let alone how an organism made up countless cells of many diverse types changes over time.

Still, enough is known to make inroads. We can target senescent cells for selective destruction. We can replace mitochondria. We can reprogram epigenetic patterns. And so forth. We can have opinions on how well any specific class of therapy will perform, but only by earnestly trying a given approach - building the therapies, conducting the clinical trials, and bringing drug into widespread use - will we actually find out how well that approach works.

As recent history demonstrates, the creation of novel therapies is a slow process in the present environment of medical regulation. Ten years is a rapid pace for the move from idea to first clinical trial. Another decade might pass between that first trial and commercial availability of the resulting drug for the average patient. Success for any given line of research is not inevitable. Viable therapies can be completely ignored because the drugs involved are generic, or the approach otherwise cannot be effectively patented and monopolized. A long road lies ahead, given the way in which medical research and development is presently conducted.

Past, present and future perspectives on the science of aging

Juan Carlos Izpisua Belmonte: In the next decade, I expect aging research to move from describing decline to restoring function. High-resolution human datasets, from single-cell and spatial maps to longitudinal studies, will provide a clearer picture of how aging progresses across tissues. At the same time, systemic biology will become even more important, with interorgan communication and circulating signals serving as key therapeutic entry points. Clinically, biological age measures will help to personalize prevention and allow earlier intervention. In the long term, I am hopeful that these developments will reshape medicine.

Steve Horvath: Over the next 10 years, I expect the field to shift decisively from measuring aging to modulating it in humans. I hope that epigenetic clocks will continue to mature into tools for evaluating interventions in individuals and even at population scale. My hope is that the aging field will identify safe, well-tolerated interventions that are capable of rejuvenating multiple human organ systems.

Bérénice A. Benayoun: In the next decade, I think the future of our field will be precision geroscience - understanding what shapes aging trajectories and which levers can be potentially acted upon to promote long-term health, not only based on private unique genetic variation but also other important factors that we are just beginning to appreciate/

Steve N. Austad: I see a takeover by massive omics. I am not suggesting this is a bad thing. It will certainly lead to a personalization of health and medical treatments, but I don't think it will lead to the kind of breakthrough that something like antibiotics represented. I think there will be more interventions on the market over that time (mostly supplements) - some might even be effective, although I doubt they will outdo what the best lifestyle choices do now. Real breakthroughs, if they come, will be further out than 5-10 years.

Terrie E. Moffitt: Over the next 5-10 years, I envision aging research evolving into an era of close integration between basic and clinical sciences, much like what has been achieved in hypertension, diabetes and cancer research. As our understanding of the molecular mechanisms that regulate aging deepens, we will see the identification of diverse therapeutic targets and an acceleration in the development of drugs, vaccines and other interventional strategies.

Guang-Hui Liu: The coming decade will probably see a shift towards precision geroscience. Multidimensional aging clocks may become clinically useful tools for quantifying biological age and intervention effects. We anticipate early human trials targeting newly recognized aging drivers, and advances in gene and cell-based regenerative strategies. Critically, the field is moving towards a unified medical paradigm: targeting the root causes of aging to prevent multiple chronic conditions together, rather than individually.

Vadim N. Gladyshev: I expect to see organ- and systems-resolved aging maps and clinically qualified aging biomarkers; routine real-time biological age monitoring (omics, digital, wearables, and imaging); embryo-inspired rejuvenation cues; advances in replacement; insights from long-lived species on complex interventions that slow down aging; and advances in the theoretical understanding of aging.

Vera Gorbunova: I expect the first antiaging interventions to be approved and introduced to clinical practice. I see aging biomarkers to become a routine part of a health check-up linked to individualized recommendations on improving healthspan. I also expect the development of safe interventions focused on restoring a more youthful epigenome, and preventative strategies to enhance genome stability and improve DNA repair to become available.

David A. Sinclair: I expect the emergence of interventions that treat common diseases by resetting cellular age and allowing the body to heal itself. This will include Yamanaka factor mediated epigenetic reprogramming, due to be tested in humans in 2026, followed by epigenetic editing, small-molecule reprogramming drugs and AI-guided therapies. Within 10 years, I foresee whole-body rejuvenation.

George A. Kuchel: I firmly believe that the future of geroscience, and also its most important impact, will be in the prevention of multiple chronic conditions, which are among the most prevalent and typical features of aging in humans.

John W. Rowe: First, there will be a dramatic increase in the number of clinical trials focused on senescence and age-related disorders with interventions arising from geroscience. Second, we are lagging behind in care of older persons and geriatric medicine continues to suffer severe workforce inadequacies, especially for those with low or middle income. Societies must recognize the need and develop incentives, including financial, to bolster all facets of the eldercare workforce including public health, acute care and long-term care. Third, we have largely viewed aging as an accumulation of deficits and have systematically neglected the valuable capabilities that older people bring to society.

Oskar Hansson: In the space of neurodegenerative diseases, I think we are now moving into the therapeutic era, and I hope that the research community will develop several effective and safe interventions for these devastating brain diseases. Personally, I have especially high hopes for different genetic medicine approaches.

Anne Brunet: The field is moving forward very rapidly, and it is amazing to be part of it! I think there will be several translational breakthroughs in the next 5 to 10 years, notably for devastating age-related diseases such as Alzheimer's disease. Research-wise, it will be very cool to see what happens because so much more is feasible at the organismal level, and it will be an era of quantitative physiology that can be done at scale.

Ming Xu: In the next 5 to 10 years, I expect that the field of aging research will make incredible progress in these three directions. (1) I expect to see a significant rise in large-scale, human clinical trials for geroscience interventions. (2) Single-cell and spatial omics technologies will allow us to reveal the cellular and tissue-specific heterogeneity of aging. 3) AI will become an indispensable tool for aging research. AI and machine-learning models will be used to understand the complexity of multiomics data, identify novel aging targets and design personalized therapies.

Eiji Hara: Cellular senescence research is currently attracting considerable attention, with growing evidence that senescent cells are deeply involved in aging and various age-related diseases. Many studies suggest that targeting senescent cells could help to prevent or treat age-related conditions. Over the next 5-10 years, I expect we will gain a clearer understanding of several critical questions: which types of senescent cells drive specific pathologies, what are the optimal strategies for selective elimination versus functional modulation of these cells, and what are the potential risks of senolytic interventions.

Jing-Dong J. Han: I envision the next decade as the era when aging research becomes a predictive science. Big data will provide the 'language' of aging - a comprehensive, high-resolution dictionary of biological changes. AI models will be the 'translator', enabling us to read this language to forecast health trajectories, identify vulnerabilities and design personalized interventions long before clinical symptoms appear. The goal will be to move from treating age-related diseases to preemptively managing the aging process itself.

Felipe Sierra: As with all other areas of human activity, the field will be dominated by AI and other computer-based approaches to translate the biology of aging into interventions. In addition, I believe the field will succeed within the next 5 years at identifying predictive and clinically useful biomarkers that will take us into a more quantitative stage of research. I fear that, combined, AI and biomarkers will 'suck up the oxygen' from more basic mechanistic research, and this in turn will lead to progressively diminishing returns from AI and biomarkers.

Matt Kaeberlein: I am optimistic that the importance of geroscience will continue to gain recognition, and lead to greater investment from both public and private sectors. I expect substantial engagement from major pharmaceutical companies and anticipate the first FDA approval for a drug that slows aging, probably in companion animals. That milestone would mark a turning point for translational geroscience. Clinically, the landscape will remain frothy for a while. Some longevity clinics already practice evidence-based medicine, whereas others promote unproven or even unsafe interventions. Over time, I expect consolidation around data-driven, ethical standards.