Note: This is commentary and scientific context only, not medical advice.
Image credit: MIT Technology Review.
Image credit: MIT Technology Review.
An MIT Technology Review article about our work was published recently (December 22, 2025). Although Vladimir Leshko and Ivan Morgunov provided extensive interviews, the final piece didn’t go as deep into the details as we would have liked.
We did not, of course, request any changes to the experts’ opinions; those are subjective viewpoints and stand as they are. However, we feel it is important to address the broader expert commentary in detail, as some statements about our technology (without specific reference to our protocol, delivery method, or design choices) contributed to potential confusion for some of the readers. Our goal in doing so is not to suppress criticism but to minimize future distortions.
Quote: “But some experts are concerned that the trial involves giving multiple gene therapies to small numbers of healthy people. It will be impossible to draw firm conclusions from such a small study, and the trial certainly won’t reveal anything about longevity, says Holly Fernandez Lynch, a lawyer and medical ethicist at the University of Pennsylvania in Philadelphia.”
We fully acknowledge the valid concerns raised by experts like Holly Fernandez Lynch regarding the administration of multiple experimental gene therapies to small numbers of healthy volunteers. Indeed, such small-scale studies (n=10–15) cannot provide statistically robust conclusions about long-term safety, effect reproducibility, or any meaningful impact on longevity, and we make no claim that this follistatin + VEGF combination is a ready-made “longevity therapy.” It is positioned only as a potential early step toward modulating age-related markers, primarily body composition (muscle mass via DEXA, body fat percentage, and strength), where we anticipate large, observable phenotypic changes.
We also recognize the deeper ethical questions highlighted by critics: whether it is appropriate to expose healthy (or aging but otherwise healthy) individuals to the known and unknown risks of gene therapies, including potential immune responses, off-target effects, or long-term uncertainties, even when the technologies carry serious safety questions, even in life-threatening disease contexts. These are legitimate points, and we do not dismiss them lightly. All participants in our trial are fully informed and provide voluntary consent after detailed risk disclosure, and participate under the oversight of an institutional review board. We prioritize participant safety through non-integrating vectors, careful dose escalation, and rigorous monitoring.
At the same time, we believe there is a compelling ethical case for pursuing accelerated, innovative pathways in this field. Traditional regulatory processes, while essential for ensuring broad safety and efficacy, are inherently slow and resource-intensive, often taking many years or decades for therapies targeting age-related decline. Meanwhile, aging itself causes immense suffering: over 120,000 people die daily from age-related causes worldwide, and millions more endure progressive loss of function, independence, and quality of life. In this context, deliberately slowing progress on interventions that could meaningfully address sarcopenia, vascular decline, and other hallmarks of aging, when preliminary evidence from animal models is promising, raises its own ethical questions. We view inaction or excessive caution as potentially unethical when the human cost of delay is so high.
This is why we deliberately pursue this paradigm — prioritizing substantial effect sizes (~20–50%+ on key biomarkers) detectable even in small series — because it dramatically accelerates iteration cycles and enables rapid elimination of non-viable approaches. This approach draws inspiration from the early stages of breakthrough therapies, where potent, unambiguous effects were first evident in individual patients or small groups before large-scale trials (insulin, antibiotics, Viagra). Traditional large Phase III trials with hundreds of participants are essential for detecting subtle effects (5–15%) where high statistical power is required to separate signal from noise, but they are often unnecessary and even counterproductive at the early proof-of-concept stage for interventions expected to produce significant outcomes.
We recognize both the strengths and limitations of each strategy: small-n with large effect sizes offers speed, low cost, immediate visual feedback on success or failure, and agile adaptation; large cohorts provide reliability, detection of rare adverse events, and generalizability. We do not reject the latter, but at the current stage in well-regulated jurisdictions, our focus on rapid, high-signal iteration is critical. If an intervention is truly potent, it will declare itself unambiguously even in a single person or small group. If it does not, we learn that lesson quickly and move forward. This is not a dismissal of risk or ethics, but a deliberate, evidence-informed strategy to achieve meaningful improvements in aging biology as efficiently and rapidly as possible, while always placing participant welfare first.
Quote: “VEGF is a powerful compound, says Seppo Ylä-Herttuala, a professor of molecular medicine at the University of Eastern Finland who has been studying VEGF and potential VEGF therapies for decades. He doesn’t know how many people have had VEGF gene therapy in Russia. But he does know that the safety of the therapy will depend on how much is administered and where. Previous attempts to inject the therapy into the heart, for example, have resulted in edema, a sometimes fatal buildup of fluid. Even if the therapy is injected elsewhere, VEGF can travel around the body, he says. If it gets to the eye, for example, it could cause blindness. …And while the therapy has been approved in Russia, there’s a reason it hasn’t been approved elsewhere, says Ylä-Herttuala: The clinical trials were not as rigorous as they could have been. While “it probably works in some patients,” he says, the evidence to support the use of this therapy is weak…”
We fully respect Professor Seppo Ylä-Herttuala's expertise; he is a true pioneer in cardiovascular gene therapy, having been the first to apply adenoviral VEGF gene transfer to human arteries in 1995, leading multiple Phase I–III trials, and founding Ark Therapeutics (now FinVector). His long-standing caution about VEGF's potential risks is well-founded: as a powerful angiogenic factor, it can induce edema, excessive vascular permeability, and unwanted neovascularization, particularly with systemic delivery, high doses, or viral vectors targeting sensitive areas like the heart or coronary arteries, where early trials indeed reported serious complications.
That said, the concerns expressed in the article appear to reflect experience with those earlier, more invasive approaches (primarily adenoviral or catheter-based intracoronary/intramyocardial delivery), rather than the specific technology Unlimited Bio is employing: intramuscular injections of plasmid DNA encoding VEGF165. This non-viral, plasmid-based method is designed for predominantly local expression in skeletal muscle, with minimal systemic spread of the plasmid or transgene product, unlike viral vectors that can spread widely.
Post-marketing surveillance and long-term follow-up studies (up to 5 years) in over 200+ patients with peripheral artery disease have shown no significant increase in systemic complications such as edema, malignancies, impaired vision, or major cardiovascular events compared with controls, supporting a favorable safety profile for this delivery format.
For additional context, many practices already common in the longevity and biohacking communities, such as intensive hyperbaric oxygen therapy (HBOT) courses of 50–60 sessions, as publicly discussed by Bryan Johnson, can elevate circulating VEGF levels substantially, theoretically carrying similar risks of unwanted neovascularization in eyes or other tissues. Yet these endogenous VEGF boosts are pursued without the same level of regulatory scrutiny or long-term monitoring. Against that backdrop, a targeted, local plasmid VEGF approach may offer a more controlled and predictable profile than some widely adopted biohacking interventions.
In summary, we value Professor Ylä-Herttuala’s decades of experience and share his general concern about the potency of VEGF. At the same time, the risks he highlights are most relevant to high-expression viral vectors and systemic or cardiac delivery — approaches quite different from our intramuscular, plasmid-based VEGF165 platform, which produces lower and predominantly local expression. We believe this distinction matters and is supported by post-approval safety data accumulated over more than a decade. Still, we do not downplay the remaining uncertainties: any gene therapy carries risks. That is why we conduct our work under strict monitoring, informed consent, and regulatory oversight.
Quote: …At any rate, he adds, VEGF will only support the growth of blood vessels—it won’t tackle aging. “VEGF is not a longevity drug,” he says.
We appreciate Professor Seppo Ylä-Herttuala's perspective, yet we do not intend to claim that VEGF (alone or in combination with follistatin) is a proven life-extension intervention in humans. No such longevity drug currently exists with robust human evidence, and aging is a multifaceted process that will likely require dozens of targeted interventions (if we are fortunate). Our approach treats VEGF as one potential "brick" in a much larger structure, specifically aimed at supporting microvascular health, which declines with age through mechanisms like capillary rarefaction and impaired VEGF signalling.
Supporting evidence for the relevance of VEGF signaling in aging biology comes from high-impact preclinical studies, most notably Grunewald et al. (Science, 2021), which demonstrated that age-related VEGF signaling insufficiency (driven by increased decoy receptors like sFlt1) contributes to capillary loss, reduced tissue perfusion, and multiple hallmarks of aging (e.g., mitochondrial dysfunction, endothelial senescence, inflammaging). Restoring youthful VEGF signalling in aged mice prevented these changes, improved organ function, and extended median lifespan by 19–35% while enhancing healthspan metrics (reduced fat accumulation, sarcopenia, osteoporosis, etc.). This aligns with broader literature on microvascular rarefaction as a contributor to systemic aging, including reduced microvessel density limiting oxygen/nutrient delivery and disrupted VEGF signaling, exacerbating endothelial dysfunction. In humans, associations have been reported between VEGF gene polymorphisms and longevity differences (e.g., in Italian cohorts), further suggesting a role for this pathway in lifespan variation, though causality remains to be established.
In summary, we fully agree that VEGF is far from a standalone solution for longevity or aging. Rather, we view VEGF as one mechanistically plausible component, grounded in solid preclinical data and supported by emerging human associations, that may contribute to a broader, multi-pronged strategy. We remain committed to careful, evidence-based exploration, clear communication, and incremental progress without hype or overpromising.
Next, the article quotes the professor saying he is not optimistic about the hair approach, adding that hair growth is, quote, “largely hormonal.”
Regarding the professor's comment that hair growth is "largely hormonal," this is a reasonable simplification for the core mechanism of androgenetic alopecia (AGA), where DHT sensitivity drives follicle miniaturization. However, the full picture is multifactorial: age-related changes, including reduced perifollicular vascularization, capillary rarefaction around follicles, hypoxia, and lower VEGF levels in alopecic areas, can amplify and sustain the process beyond purely hormonal factors.
Minoxidil, one of the two gold-standard treatments for AGA, alongside finasteride, works in part by upregulating VEGF expression in dermal papilla cells, promoting perifollicular angiogenesis, increasing follicle size, and supporting regrowth (as shown in multiple studies since the late 1990s). Experimental models also link VEGF restoration to improved hair density and faster regrowth.
Another point could be related to the "DHT diffusion/washout" hypothesis that improved perifollicular blood flow could, in theory, facilitate faster clearance of DHT and other metabolites from the follicular microenvironment, thereby potentially lowering local androgenic exposure and mitigating damage. While direct clinical evidence for this specific mechanism remains limited, the underlying logic is biologically plausible: enhanced perfusion reduces metabolite stagnation and hypoxia around the follicle, which may contribute to sustaining the miniaturization process in AGA.
In this context, local VEGF delivery (as Unlimited Bio is exploring) represents a reasonable complementary approach to existing anti-androgen therapies, potentially addressing the microvascular component of age-related follicle decline. We emphasize that this is not positioned as a replacement for DHT blockade but as a targeted adjunct, grounded in established mechanisms of perifollicular vascularization and supported by preclinical and clinical precedents.
And he points out that we already have some treatments for hair loss and erectile dysfunction. While they aren’t perfect, their existence does raise the bar for any potential future therapies—not only do they have to be safe and effective, but they must be safer or more effective than existing ones.
We appreciate Professor Ylä-Herttuala's valid point that established treatments for hair loss (and erectile dysfunction) already exist, and any novel therapy must not only demonstrate safety and efficacy but also offer meaningful advantages, whether in effectiveness, convenience, tolerability, or duration, over current standards to justify its development.
This is precisely the gap Unlimited Bio aims to address with a potential scalp-targeted plasmid VEGF gene therapy protocol: to provide a longer-lasting, low-maintenance alternative to the current gold-standard topical minoxidil, which requires daily (often twice-daily) application for the whole life. Discontinuation of minoxidil typically leads to rapid reversal of benefits within months, while common side effects include local irritation (itching, redness, dryness), unwanted facial/body hair growth, initial shedding, and, in rare cases of excessive absorption, systemic issues such as tachycardia or edema.
Moreover, there is a significant difference in the mechanism of action of these therapies. To clarify, while minoxidil does upregulate VEGF expression and contributes to increased blood flow around hair follicles, its primary vascular effect is vasodilation—widening existing blood vessels—rather than robustly inducing the formation of entirely new capillaries (true angiogenesis). In contrast, direct VEGF gene therapy is designed to drive angiogenesis more effectively, building new capillary networks to counteract the well-documented capillary rarefaction (progressive loss and reduction in density of perifollicular blood vessels) that occurs both in AGA and with natural scalp aging. This rarefaction, confirmed in multiple studies, including histopathological analyses of AGA scalps and aging models, limits nutrient and oxygen delivery to follicles, exacerbating miniaturization, hypoxia, and hair loss over time. Therefore, strategies that actively increase capillary number and density (rather than just dilating what's already there) could offer a superior, more physiological approach to restoring and maintaining follicular health, especially in aging or alopecic scalps where vessel loss is a key contributor to progression.
In principle, a localized intramuscular or intradermal plasmid-based VEGF approach could offer several potential advantages:
- Duration: By promoting sustained local VEGF signaling and perifollicular angiogenesis, the effect might persist for months to years after a single course of injections (drawing analogy from post-marketing data on VEGF gene therapy for ischemia, where improved blood flow has been documented for several years, and from preclinical models showing enhanced follicle size and regrowth with VEGF upregulation).
- Compliance: A rare procedure (potentially once every several years) would eliminate the need for lifelong daily topical application.
- Mechanism: Minoxidil mainly dilates existing vessels, while targeted VEGF gene therapy directly drives angiogenesis, actively increasing the number and density of perifollicular capillaries, improving nutrient/oxygen delivery, and (though evidence remains indirect) facilitating better local clearance of DHT and other metabolites.
Of course, this remains an experimental concept, and we fully recognize that trials are essential to validate key aspects: actual duration of effect, comparative superiority (or added benefit) over minoxidil, and the absence of local off-target effects in the scalp (such as unwanted neovascularization, irritation, or other complications). Should the emerging data support these hypotheses, this could represent a meaningful incremental improvement for patients who struggle with minoxidil tolerability or adherence or who seek combination strategies alongside anti-androgens.
We deeply respect the concerns raised by experts, and we fully share their emphasis on rigorous safety, robust evidence, and the high bar set by existing therapies.
Our approach is deliberately incremental: we prioritize rapid, high-signal proof-of-concept in small series under ethical oversight in regulated jurisdictions, while fully acknowledging that large-scale assessments are essential for reliability, rare event detection, and broader approval. Also, we make no exaggerated claims that this combination (follistatin + VEGF) is a "longevity drug" or magic solution, but it is one potential early component among many needed to address complex hallmarks of aging, such as microvascular and muscular decline.
Ultimately, everything we do is driven by a single goal: to tackle the problem of aging as safely, as quickly, and as effectively as possible, minimizing unnecessary delays in a field where time is measured in human lives and quality of life lost every day. We proceed step by step, with full transparency, participant welfare as the absolute priority, and openness to expert input, scrutiny, and collaboration.
Have an incredible New Year, and thank you for engaging with the details!
Have an incredible New Year, and thank you for engaging with the details!