I’m a cliche, I know. Like so many privileged, middle-aged men today, I’m increasingly obsessed with my health span. It’s not just about extending lifespan anymore but rather ensuring that quality of life remains high until the end—which, ideally, comes moments after I finish an ice-cold gin martini, though not too soon. So, I have embraced the longevity movement in moderation, avoiding the extremes that Bryan Johnson and company insist are essential, while tweaking my lifestyle at the edges for maximum impact. One such effort: I took a genetic test in August 2024 to see which markers for disease I might carry. I was not unduly worried; my family is remarkably healthy. My mother, nearly 94, has no chronic medical conditions and still lives alone at home, and my father was completely fit until just months before he died at 91.
Even so, I was unprepared for the news. Sure enough, the test turned up no worrisome markers for cancer, Alzheimer’s, or the like. More intriguingly, it flagged a mutation known as KL-VS, which I learned is estimated to occur in perhaps as few as one or two in 20 people. “You are a lucky, lucky man,” the doctor told me, with theatrical flair
It was good news. My genetic quirk bolsters the levels of a naturally produced protein called Klotho, which has become one of the longevity industry’s current obsessions. Klotho is extraordinary, if still only partially understood: a gene that has emerged as the loudest buzzword in age-fighting medicine. Forget stem cells. The true pioneers are jonesing for a jab of the stuff, and a raft of entrepreneurs are jostling to become the go-to providers of this bleeding-edge therapy.
It has taken a while. Klotho was discovered in the late 1990s, by accident, by a group of Japanese scientists who were tinkering with the genes of mice. All mammals produce the protein; in humans, the gene sits on chromosome 13. The lead scientist stumbled onto a startling finding: Knocking out the standard gene that instructs the body to make Klotho caused those mice to age prematurely. They lived for two months rather than the typical two years, died of diseases associated with old age, such as osteoporosis and atherosclerosis, and suffered geriatric memory loss. The scientist, Makoto Kuro-o, quickly recognized the potential impact of his discovery. He named the gene Klotho after the Greek goddess and daughter of Zeus; she’s one of the trio known as the Fates and spins the thread of life. Kuro-o spelled it with a “K” rather than a “C,” as a nod to his own name.
“It’s now referred to as the anti-aging gene,” says Joe Sinkule, a Florida-based scientist who has spent the past six years working on treatments centered around the protein. Put simply, it appears to be highly protective for many of our organs, the brain included, as well as the body’s overall functioning. If the body were an army, Klotho would be a brigadier general, directing operations from a high-ranking post. Various forms help preserve kidney health by regulating calcium and phosphate levels, for example, and support mitochondria—the energy plants inside each cell—so they work more efficiently. It helps keep the vascular system flexible enough to reduce the risk of heart attack or stroke, maintains brain plasticity, and may stave off Alzheimer’s. The problem, of course, is that it naturally ebbs with age, just when the body needs it most. “It’s what I call the Klotho clock,” Sinkule says.
Klotho crests in youth before settling in adulthood and dwindling in middle age. “By the age of 80 or 90, it’s almost not measurable in the blood,” Sinkule says, adding that readings in early onset Alzheimer’s patients of any age might also be undetectable. Testing is available with different numerical scales, and my score, at age 51, fell within the middle of the top tier
I have KL-VS to thank. This variant prompts the body to keep churning out Klotho at high levels, regardless of chronological age. “Those people are very lucky: They live longer, they are healthier, they’re resistant to many diseases of aging, and they are smarter by an IQ difference of at least six points…. It’s [also] a tumor suppressor,” says Carmela Abraham, a Boston-based researcher and the chief science officer of Advantage Therapeutics and Klothea Bio, two new entrants in the field. What’s more, Abraham says, KL-VS carriers may also be protected against Alzheimer’s, even when they carry other risk factors such as the APOE4 gene.
A good way to understand the KL-VS advantage is to think of the body as a biological photocopier. Imagine taking a piece of paper and xeroxing it; the first copy is an exact replica. Now take that copy and xerox it once more, and keep going until you are squinting at the pixelated, fuzzy text of the 20th dupe. Much the same happens in our bodies as cells replicate over time: Errors are introduced, and they lead to problems, including cancer. Like a vigilant technician, Klotho steps in at each stage and adjusts the focus back to the original, ensuring that those biological copies remain accurate and legible. The issue, of course, is that Klotho levels decline precisely when that assistance is most needed—except in those of us who carry KL-VS, where the higher levels appear to fight aging at the cellular level. Strangely, one copy of KL-VS is fortuitous, but inheriting one from each parent can backfire, reducing Klotho levels and curtailing lifespan for reasons scientists do not fully understand. My only copy came courtesy of my mother.
Klotho, then, offers remarkable benefits to the body at high levels, at least according to a growing number of researchers. But there are also natural ways to elevate it, including exercise. Given its apparent upside, why hasn’t it been commercialized sooner? In part, the answer is technical: Large proteins such as Klotho are difficult to manufacture in a lab. They also have short half-lives, meaning even if a treatment had been developed decades ago, it might have required twice-daily injections to be effective. New techniques like mRNA—the term that became a household name during the Covid pandemic—are making Klotho therapy more viable. The focus now is on regulatory approval through disease treatment. The F.D.A. won’t sign off on new drugs based on indications around lifespan—because aging itself is not a disease. But if Klotho can be turned into an injection that treats a specific condition, it will, presumably, be much easier to introduce to the mainstream.
That is the path Joe Sinkule has chosen with his firm, Klotho Neurosciences. The 46-year veteran of drug development was first contacted four years ago by a high-net-worth individual with polycystic kidney disease that risked tipping over into chronic renal failure. The would-be client learned that artificially increasing his Klotho levels could potentially short-circuit the problem and wanted Sinkule’s help finding a company that could produce it for him. The request prompted Sinkule to explore the protein’s therapeutic potential himself. “The more I read, the more [it] sucked me in,” he says. His well-funded start-up centers on promising animal-trial data around A.L.S., the disease that took actor Eric Dane’s life last February, at age 53. The data from those animal trials showed a 400 percent uptick in lifespan, largely thanks to Klotho’s protective impact on the brain. Sinkule says the first recipients of the experimental therapy should be scheduled before the end of the year, and that the treatment is roughly two and a half years away from market.
We have a pandemic of Klotho deficiency
Abraham’s experience with Klotho is different. She has been working on it for more than 20 years and is preparing a Phase 2 clinical trial for an Alzheimer’s drug and a Phase 1 clinical trial of an mRNA-based regimen to help otherwise healthy adults elevate their Klotho levels for age-fighting benefits. That trial proposes testing biomarkers from blood and urine at the outset, then comparing chronological and biological age over time. Her boss, Dr. Agustin Fernandez Santana, has put himself forward to be a guinea pig in the interim. The 50-year-old C.E.O. has been receiving IV infusions of Klotho-boosting serums for two years overseas, tinkering with dosages to see what is most effective. “I have a very unhealthy lifestyle, I don’t exercise, and I try to enjoy life as much as I can,” he says with a laugh. “I’m not proud of it.”
Using a blood test that measures picograms per milliliter, his original levels were 980, or normal-to-low. Within 24 hours of his first shot, they hit 2,700. He has received infusions every four months or so—“It’s really hard to sleep the night of the treatment because you’re not tired”—and his last reading was 4,000. Santana evangelizes for the protocol by upending the equation. In his view, the goal isn’t to lift Klotho levels unnaturally but to correct a shortage in our bodies. He points to studies including healthy centenarians that consistently report higher-than-typical Klotho levels, even at 100 or older. “For a long time, we didn’t know scurvy was caused by a vitamin C deficiency. We had very low levels of vitamin D. The same thing is happening to Klotho. Everybody is low, so the deficiency becomes normalized—‘normal’ is deficient. The magic number is about three times that… I’m not tinkering with nature. We have a pandemic of Klotho deficiency.”
Red tape and regulations preclude him from offering that treatment stateside now, but it is available in some jurisdictions, including the libertarian microstate of Próspera in Honduras. Each infusion costs about $35,000. Próspera is also one of the locations for partner clinics of Minicircle, another longevity start-up readying its own Klotho gene therapy. Mini-circle already markets the muscle-increasing Follistatin, or FST-344, for $25,000 per dose and has more than 60 patients trialing its Klotho-based jab. Mac Davis is Minicircle’s founder. “Klotho is the darling of the longevity industry right now,” he says. “We’ve seen improved fluid intelligence, decreased brain fog and neuro inflammation. We’ve seen benefits from people with long Covid… and kidney function is greatly improved.”
Like me, 34-year-old Davis is fortunate to carry one copy of KL-VS, but he still took a trial dose of his own formula to see whether it would be impactful. He talks of the sensation much like psychedelic acolytes describe their experiences. “It felt like my mind did when I was 12—I hadn’t realized how much it had aged and gotten into its set patterns. I looked at everything with a fresh pair of eyes. When I listened to music, it was as if I had never heard [it] before.”
Neorgana is another clinic currently providing Klotho treatments. It’s located in Mexico, where regulations are favorable to such experimental work. The Bahamas and Panama have become longevity hot spots for similar reasons. Omar Novelo, who runs the firm, says Klotho regimens are now 10 to 15 percent of his business. Neorgana has two types of therapy to choose from: an intra-nasal form, aimed squarely at the brain and associated cognitive improvement, for $65,000, and a whole-body IV for $240,000. A 60-something retiree came for the former a few months ago as part of an overall longevity package that also included stem-cell therapy. “He’s starting a new company now. He was like, ‘I retired, but now with this enhanced brain function, why wouldn’t I develop a new venture?’ ” Novelo says. Likewise, a couple in their 80s came seeking treatment for the wife’s Alzheimer’s, which was advanced enough that her husband was effectively a full-time caretaker. Neorgana treated her with a focus on increasing Klotho levels. “Now this lady is having a fully functional life,” Novelo says. “She’s still living with Alzheimer’s but has been asymptomatic for a couple of years.” (Robb Report was unable to independently verify that claim.)
It sounds like a miracle drug, of course, which is why a healthy dose of caution is warranted. But it’s hardly surprising that the people keen to monetize Klotho are so bullish about its potential. So, how does the rest of the longevity world view their assertions?
Dr. Michael Zemel, chief scientific officer of Kinexum, a Harpers Ferry, West Virgina–based consulting firm with specialty in this area, has no financial stake in any Klotho start-up and is far more skeptical. Zemel points to a recent 4,000-person study on extreme human longevity. Those with exceptionally long lives did, indeed, have high Klotho levels. “If you have a lot of Klotho, does it predict a longer lifespan? Unfortunately, the answer is not even close. It’s just a flat no.” he says of that study. “It’s not… [an] elixir of life.”
He acknowledges that the protein has beneficial effects on the body, including reducing inflammation, or what is known as inflammaging. But he believes it is likely a contributor to life-extension, not the secret itself. If Klotho helps stave off age-related illnesses, from cardiovascular disease to cancer, longevity may be an inevitable side effect, rather than its purpose. Would the 72-year-old undergo IV therapy like that proposed by Minicircle and others? “If I thought Klotho would do it for me, I would be on a plane,” he says, adding that there’s also no data on the safety of artificially juicing Klotho levels in people without KL-VS. “There are laws of unintended consequences that we may not fully understand.”
Lynne Chang is equally cautious. She is V.P. of product development at longevity firm Elysium Health. “I would recommend against it. I just don’t think the science is there yet, and I wouldn’t take it, personally,” she says, pointing to the lack of data on effective—or even dangerous—dosage levels, noting that there are no human clinical-trial results to reassure her. She advises raising Klotho naturally—through exercise. “And the Mediterranean diet, or diets that are high in antioxidants and anti-inflammatory compounds,” adding that both have shown to be associated with higher levels of the protein.
Better, then, to follow Chang’s lead: Treat Klotho levels less as a magic bullet than a marker. Think of it as something like the systemic equivalent of HDL cholesterol for the vascular system—a reading that indicates general health and creates a chance to intervene, at minimum, through lifestyle changes. Almost two years after first discovering my genetic jackpot, I’ve been exercising more rigorously and regularly than at any point in the first five decades of my life. And I’ve just taken another test to see whether it has affected my Klotho levels: I’m now at the lower end of optimal, so I guess I need to work a little harder on bolstering my numbers.
