Why “reprogramming” is the buzziest approach to reversing aging right now

Earlier this week, Life Biosciences, a biotech company focused on reversing age-related diseases, announced that it had dosed its first volunteer. A person with glaucoma has had an experimental treatment injected straight into their eyeball.

The idea is to try to treat the disease—which can cause vision loss—by regenerating healthy nerves in the eye. But David Sinclair, the chairman and cofounder of the company behind the trial, hopes to go further. If the treatment can reverse glaucoma, perhaps similar treatments can reverse other diseases of aging. Maybe, just maybe, they can reverse aging altogether.

The approach is designed to work by “reprogramming” cells to a younger state. It’s one of many strategies being explored by biotech companies looking to slow and reverse the process of aging. But of all of them, it seems to be the one that is truly taking off.

Aging is complicated. As we get older, we experience so many changes across pretty much all our biological systems. Scientists have tried to categorize these effects. In 2013, one team published a seminal paper describing nine “hallmarks of aging.” That list features many of the processes scientists have attempted to target. But some of those targets have fallen in and out of fashion over the years.

Take telomere attrition, for example. Telomeres are DNA sequences at the ends of our chromosomes, often likened to the plastic caps that stop the ends of our shoelaces from fraying. When cells divide, telomeres shorten until, eventually, the DNA is vulnerable to damage.

When I started reporting on aging, telomere shortening was all the rage. Shrinking telomeres had been linked to age-related diseases of the heart and brain. Shortened telomeres were considered a sign of premature aging. In 2017 Liz Parrish, CEO of the biotech company BioViva, injected herself with an experimental gene therapy that she hoped might lengthen her telomeres.

Then it suddenly seemed to go out of style. Research continued, but all the excitement within the aging and longevity community seemed to move on to another hallmark. (Parrish also continued with self-experimentation; she calls herself “the most genetically modified person on Earth.”)

That hallmark was cellular senescence. This happens when cells stop dividing but don’t die, instead entering a “zombie” state in which they churn out chemicals that can cause harmful inflammation.

Senescent cells gradually accumulate in pretty much every organ studied, where they are thought to contribute to age-related damage. Why not just periodically clear them out? When a team of scientists took that approach in mice in 2011, they found they could delay the onset of age-related conditions like cataracts and hunchback. The treated mice even looked younger.

But when scientists at Unity Biotechnology trialed a similar approach in people with osteoarthritis and an age-related eye condition in the late 2010s and early 2020s, the results were disappointing. The company laid off every employee in May last year and has since shuttered entirely.

Again, that doesn’t mean senolytic drugs that target “zombie cells” won’t work. But it feels as if many in the field have moved on. These days, the buzz is all about ✨reprogramming✨.

The idea here is to essentially return cells to a young state. It’s based on the Nobel Prize–winning discovery that four genetic factors can turn an adult cell into a stem cell, which can be encouraged to develop into pretty much any other cell type.

Some promising studies in mice suggest that this approach might help wind back the clock. It seems to improve tissue healing, restore vision, and even improve learning and memory.

Running parallel to all this research are repeated injections of hundreds of millions of dollars in funding. In 2021, my colleague Antonio Regalado reported on the founding of the biotech company Altos Labs to pursue reprogramming for rejuvenation.

Altos was funded by the billionaire Yuri Milner—reportedly along with Jeff Bezos, among others—to the tune of $3 billion, a previously unheard-of figure for a biotech startup. Other well-funded companies have since sprung up in this space.

There’s Retro Biosciences, for instance, which is pursuing reprogramming (among other approaches) in an effort to add 10 years of healthy life to human lifespans. Retro’s launch was supported by $180 million from OpenAI’s Sam Altman. Last month, the company announced a valuation of $1.8 billion.

NewLimit, another billionaire-backed biotech exploring reprogramming, says it has promising results from research in mice. It plans to trial a drug designed to rejuvenate the liver in people next year. Last week, the company announced it had raised $435 million toward reaching that goal, among others.

Life Biosciences, which was founded by the Harvard biologist David Sinclair, most recently secured $80 million to support its research. The eye trial is now officially underway, but Sinclair also has plans for whole-body rejuvenation. Earlier this week, he told my colleague Antonio that he plans to test a “highly, highly confidential” oral reprogramming drug as part of a $101 million competition organized by the XPrize Foundation. 

Reprogramming has certainly caught the attention of scientists, biotech companies, and investors. Studies in mice are hugely promising. Human trials are launching. And research in the field has billions of dollars’ worth of support.A lot of people in the field are really excited about reprogramming. But it comes with risks. And we still don’t know if it will work. The question now is: Do we finally have a rejuvenation drug within reach? And if not, what will the next research trend look like?

This article first appeared in The Checkup, MIT Technology Review’s weekly biotech newsletter. To receive it in your inbox every Thursday, and read articles like this first, sign up here.

Opinion: I’ve spent 40 years in research. I have never seen a threat to science like the new grantmaking rule

Childhood leukemia, a likely death sentence when I was a medical student, is now survivable for most children. Cancer immunotherapy is extending life for many who would have died a decade ago. New technology is letting us repair genetic diseases at their source. The same American scientific research enterprise that produced these breakthroughs also gave us GPS, the modern semiconductor, and the early architecture of the internet.

All of it came out of an American research enterprise that the federal government is now proposing to fundamentally rewire for no good reason.

Read the rest…

How a diabetes conference sparked a controversy

The expulsion of five diabetes experts from the American Diabetes Association meeting in New Orleans earlier this week caused quite a stir. Many in the diabetes research community expressed shock and disbelief that their colleagues were threatened with arrest for passing out paper copies of an editorial. After a few days of doubling down in the face of significant backlash, the ADA did formally apologize on Wednesday. But is their mea culpa too little, too late?

In this week’s STATus Report, I chat with STAT cardiovascular disease reporter Elizabeth Cooney. She was in New Orleans for the diabetes meeting, and we discussed what exactly happened, what the reaction was like on the ground, what it says about the climate of biomedical research in the second Trump administration, and more. 

FEEL-GOOD: A Multicenter Trial of a Mindfulness-Based Group Therapy in Young Adults With Early Psychosis

Conditions: Early Onset Psychosis; First Psychotic Episode Within the Last 5 Years; First-episode Psychosis; Schizophrenia Spectrum Disorders (SSD); Psychosis; Psychosis NOS; Randomized Controlled Trial (RCT)

Interventions: Behavioral: FEEL GOOD; Other: Treatment as Usual (TAU)

Sponsors: Stephanie Mehl; German Research Foundation; Universitätsklinikum Hamburg-Eppendorf; Central Institute of Mental Health, Mannheim; University Hospital Augsburg; Ludwig-Maximilians – University of Munich; Charite University, Berlin, Germany; University Hospital of Cologne; Vivantes Klinikum am Urban; Philipps University Marburg

Recruiting

An Investigator-Initiated, Randomized, Double-Blind, Double-Dummy Study to Evaluate the Adjunctive Effect of CreNeuroS™ CNS Fish Oil Plus Softgels in Patients With Major Depressive Disorder Receiving Escitalopram.

Conditions: Adjunct in the Treatment of Depressive Disorder

Interventions: Combination Product: Escitalopram (as escitalopram oxalate) tablet +CreNeuroSTM CNS Fish Oil Plus Softgels; Combination Product: Escitalopram (as escitalopram oxalate) tablet +Placebo softgels

Sponsors: Sichuan Credit Pharmaceutical Co., Ltd.; Vivotech Research Lab Pvt Ltd

Not yet recruiting

Advancing Clinical Translational Research for Profound Autism

Autism Spectrum Disorder (ASD) has emerged as a key battleground in the federal assault on science. US government leaders have systematically ignored expert advice, reanimated baseless claims about the causal role of vaccines, forwarded thinly supported hypotheses blaming ASD on parental behavior, and promoted unsubstantiated treatments. This barrage comes at a time when the prospects for dramatic near-term advances in clinical translation, particularly for the severe end of the ASD spectrum, have never been greater.

Digital Health Monitoring and Intervention Suite for Stress in Frontline Nurses: Prospective Cohort Trial

Background: Stress among health care workers (HCWs) contributes to burnout, workforce attrition, and adverse patient outcomes. Although virtual reality (VR), psychoeducation, ecological momentary assessments (EMAs), and wearables have independently shown promise in stress research, no integrated digital suite has combined controlled stress induction, intervention delivery, and longitudinal real-world monitoring in HCWs. Objective: This study aimed to evaluate the feasibility, engagement, and preliminary effectiveness of a multimodal Digital Health Monitoring and Intervention suite for Stress framework integrating VR simulation, psychoeducation, EMAs, and wearable biometrics. We examined (1) the impact of VR simulation and psychoeducation on stress outcomes and (2) associations between physiological and self-reported mental health outcomes. Methods: Ninety-nine nurses (mean age 33.7, SD 8.9 yr, 87% female) were enrolled in 2023. We conducted a single-arm prospective cohort study (NCT05923398). Using convenience sampling, participants were recruited from social media advertisements, flyers, and email notices distributed through professional listservs. Participants completed ≥2-week baseline monitoring, a single VR session (2 runs separated by a brief psychoeducation intervention), and 12-week follow-up. In-VR stress was assessed using the Subjective Units of Distress Scale (SUDS) and 4-item Moral Injury Outcome Scale (MIOS-4), with synchronous heart rate variability. Longitudinal outcomes included weekly and biweekly EMAs alongside 70 wearable-derived features. Paired tests, aligned rank transform ANOVA, and Pearson correlations informed study objectives, with P values adjusted for multiple comparisons. Qualitative content analysis classified emotional responses during and after VR. Results: VR significantly increased subjective stress across checkpoints in both runs, with attenuation in Run B relative to Run A (all <.001). No significant heart rate variability differences were observed between runs (.15). During VR, 92% (91/99) of participants felt stressed, 36% (36/99) reported anxiety or nervousness, and 51% (50/99)‐78% (77/99) endorsed anger, guilt, shame, and/or betrayal. Most (59/99, 60%) HCWs returned to an emotional baseline post-VR, although 12% (12/99) reported lingering distress. Immediate reliable improvements in anger, guilt, shame, and/or betrayal occurred for 50% (50/99)‐75% (74/99) of participants post intervention. Anxiety (mean −0.53, SD 2.34; .03) and stress (mean −3.05, SD 11.35; .01) decreased 2 weeks post intervention, but were not sustained at 12 weeks. Increased sleep restlessness was the only wearable feature showing significant changes (mean 2.46%, SD 5.43; <.001). In-VR stress correlated with 12-week real-world stress (SUDS: =0.57‐0.58; MIOS-4: =0.58‐0.61; all .01). Data completion exceeded 90%, with 71% achieving full compliance. Conclusions: This study moves beyond single-tool interventions to demonstrate the feasibility and preliminary effectiveness of an integrated, multimodal stress platform within a single coordinated framework. This trial demonstrates high engagement, short-term symptom responsiveness, ecological validity, and emotional safety. The framework provides a scalable model for proactive stress identification, skills training, and implementation in high-risk occupational settings. Randomized controlled trials are needed to establish sustained efficacy and optimize deployment for real-world implementation. Trial Registration: ClinicalTrials.gov NCT05923398; https://clinicaltrials.gov/study/NCT05923398 International Registered Report Identifier (IRRID): RR2-10.2196/54180

Examining the Social and Mental Health Benefits of Virtual and In-Person Physical Activity Intervention Among Postsecondary Students: Quasi-Experimental Study

Background: Physical activity (PA) is a promising prevention approach for supporting mental health and enhancing social inclusion among postsecondary students. However, it is unclear whether similar outcomes are realized when PA programming is delivered in-person versus virtually. Objective: Using data from a multiphase research project, the purpose of the study was to examine the influence of on-campus PA programming (virtual and in-person delivery) on mental ill health symptoms (ie, anxiety and depression), social inclusion indices (ie, social connectedness, emotional ties, and social relationship quality), and well-being. Three objectives were addressed: (1) to assess pre-post change in symptoms, social inclusion indices, and well-being for virtual and in-person delivery; (2) to evaluate whether outcome change over time differed by delivery mode; and (3) to examine whether change in symptoms and social inclusion indices predicted change in well-being for both delivery modes. Methods: Physically inactive postsecondary students experiencing mental ill health participated in a 6-week structured and supervised PA program. Pre-post intervention data were collected across 3 phases, and the analytical samples included: 1. In-person delivery (n=87; 82%, 69/84 young adults; 86%, 74/86 women; 38%, 33/86 White; 20%, 17/86 Chinese; 86%, 75/87 with mental illness; 2. Virtual delivery (n=62; 69%, 42/61 young adults; 95%, 59/62 women; 34%, 21/62 White; 21%, 13/62 South Asian; 55%, 34/62 with mental illness), and 3. Data from students who received in-person or virtual delivery: (n=92; 67%, 61/91 young adults; 90%, 83/92 women; 32%, 29/92 White; 20%, 18/92 South Asian; 59%, 54/92 with mental illness). Data were analyzed using 2-tailed paired samples tests to address objective 1, a 2 (delivery mode) × 2 (time: pre-post) repeated-measures ANOVA to address objective 2, and hierarchical regression analyses to address objective 3. Results: Both virtual and in-person PA delivery were effective for symptom reduction and social inclusion improvements across all outcomes (<.001), with moderate-to-large effects. There was no significant time × delivery mode (=0.72, ²=0.04, =.60) interaction effect. Change in social inclusion indices explained unique variance in well-being, beyond covariates (gender, mental illness, and ethno-racial identity), and symptom reduction for virtual ( = 0.75, 008001) and in-person ( = 0.72, =0.16, <.001) PA delivery. Conclusions: Online distance learning is increasing across postsecondary settings worldwide, underscoring the need for accessible, technology-enabled mental health prevention interventions. The results provide support for the effectiveness of virtual and in-person PA programming for reducing symptoms of anxiety and depression, while also enhancing social inclusion indices and overall well-being. Social inclusion indices were also a key contributor to improved well-being, emphasizing the relevance of social factors in both virtual and in-person PA-based mental health prevention strategies for postsecondary students.