Could something in my kitchen slow down the cells that make me old? Mayo Clinic’s newest press release put that question in my head, because tucked inside its roundup of seven “zombie cell” studies is “a natural compound present in tomatoes.” The compound is tomatidine. In mice that started treatment at 21 months old, it lowered frailty scores, improved performance on memory tests and cooled inflammation in the brain. The study gave it to no people. And two of the paper’s coauthors are shareholders and officers of the company that licenses patents on tomatidine’s use in muscle and metabolic health.
The Mayo announcement, carried by ScienceDaily on October 26, concedes the first point itself: “These results remain preliminary in terms of medical applications,” and “More research will be necessary to establish whether the approaches are safe and effective in people.” That admission sits under a headline saying Mayo “discovers new ways to fight” the cells that drive aging. The seven papers didn’t land together, either. They came out between late 2024 and September 2026 as part of the NIH-funded SenNet effort to map senescent cells across the body, and the release bundles a couple of years of solid lab work so it reads like one breakthrough.
The cells are worth understanding first. A senescent cell has stopped dividing and resists the signals that would normally clear it away. Many of them keep releasing a mix of inflammatory molecules that researchers call the senescence-associated secretory phenotype, or SASP. You want a few of these cells around a healing wound. Over decades, though, they pile up in the liver, skin and brain, and what they pour out nudges the surrounding tissue toward chronic, low-grade inflammation. For about ten years the field’s big idea was to kill them with drugs called senolytics. I opened the tomato paper expecting another kill switch, and it turned out to describe something else.
Quiet, not dead
Costa and colleagues in EMBO Molecular Medicine screened a small panel of natural products against senescent cells and landed on tomatidine, the sugar-free core of tomatine, a compound concentrated in green tomatoes. They mixed 0.05% tomatidine into the chow of aged mice, roughly the late sixties in human terms, and fed it for three months.
Then they tried it on human cells, specifically lung fibroblasts and brain blood-vessel cells pushed into senescence with radiation in a dish. Tomatidine showed no senolytic activity in either type. The cells kept their p16 and p21, the molecular brakes that mark them as senescent, but their SASP genes went quieter. The authors call that a senomorphic effect. So the compound sold to the public as a zombie fighter didn’t kill the human senescent cells it was tested on. It turned their volume down, and I’m honestly more curious about that than I would be about one more kill switch. (In senescent mouse cells, higher concentrations did cut cell numbers.)
The mice told a mixed but mostly encouraging story. Treated animals scored lower on a frailty index, did better on a pole test of motor coordination, spent more time exploring the new arm of a Y-maze and made fewer errors in a Stone T-maze, both memory tests. On the rotarod, a standard coordination test, they did no better than untreated mice. Fewer cells carried p16 and p21 in the liver, skin and hippocampal neurons, brain microglia were less activated, and the cells lining brain blood vessels held onto more of the tight-junction proteins that seal the blood-brain barrier. Whether those falling marker counts mean cells were cleared or just calmed is unsettled. The authors write that the precise molecular targets of tomatidine in senescent cells “have not yet been defined.”
The best paper in Mayo’s roundup follows the same quiet-don’t-kill idea down to the fuel supply. In Nature, Martini, Passos and colleagues show that senescent cells ramp up a mitochondrial pathway that turns pyruvate into citrate, ships it out through a transporter called SLC25A1, and converts it into acetyl-CoA, the raw material cells use to pry open the DNA at inflammatory genes. The mitochondria are paying for the inflammation. Blocking SLC25A1 with a drug called CTPI2 for three months delayed frailty in aged mice, improved grip strength and hanging time, and enlarged muscle fibers, though it “did not improve spine and femur bone microarchitecture.” A companion paper in Nature Communications traces a second route, with mitochondrial RNA leaking into the cell’s interior and driving the SASP. Cutting the fuel line instead of torching the cell is a lovely idea. So far it lives in mice and dishes.
Two officers of Emmyon
Here is the tomatidine paper’s competing-interests statement, in full: “CMA is an inventor on patents for the use of tomatidine in muscle health and metabolic health, which are licensed to Emmyon, Inc., where CMA and SME are shareholders and officers.”
CMA is Christopher Adams, who reported at the University of Iowa in 2014 that tomatidine built muscle and trimmed fat in mice. He and colleagues founded Emmyon to push that work toward people, using tomatidine and ursolic acid as starting points for medicines against muscle atrophy and obesity. SME is Scott Ebert, his fellow coauthor and Emmyon officer. The disclosed patents cover muscle and metabolic uses, and the authors printed them, as they should. Still, a major medical center is now promoting a tomato compound against aging, and two of the paper’s twenty authors hold equity in, and help run, the company licensing tomatidine patents. You deserve to see that beside the headline, not only in a journal’s back matter.
- 2014tomatidine builds muscle in Iowa mice
- 2020UBX0101 misses its knee endpoint
- 2024dasatinib plus quercetin misses its bone endpoint
- 2026Mayo touts tomatidine in old mice
The commercial interest goes past one small company. Nathan LeBrasseur and Sundeep Khosla are both coauthors on the tomatidine paper, and LeBrasseur is also on the IL-23R biomarker paper in the same roundup. When Mayo announced its 2024 senolytic trial, its summary said LeBrasseur was one of three researchers who “have financial interests related to this research,” interests it tied to Mayo Clinic patents and pending patents on senolytic drugs. The researchers’ stakes are personal. The patents belong to the institution, which means the clinic issuing these press releases has its own reason to want the field to succeed.
The trials in people
None of the human evidence involves tomatidine, and what exists for other senolytics is thin. In the 2024 Nature Medicine trial led by Joshua Farr and Khosla, 60 postmenopausal women took intermittent dasatinib plus quercetin, the field’s flagship senolytic pair, or a control for 20 weeks. The primary endpoint, a blood marker of bone breakdown, didn’t separate from control: a median change of -4.1% on the drugs against -7.7% on control, P = 0.611. A bone-formation marker rose 16% relative to control at weeks two and four and had faded by week 20. Only in an exploratory subgroup, the women in the top third for p16 levels in their T cells, did wrist bone density rise 2.7%. Mayo’s own summary warned about people taking quercetin or fisetin “as anti-aging agents without knowing if they have high enough senescent cell numbers to benefit.”
Industry has done worse. Unity Biotechnology injected its senolytic UBX0101 into the knees of 183 people with osteoarthritis, and in 2020 the company reported “no statistically significant difference between any arm of UBX0101 and placebo at the 12-week endpoint.” It said it would not run pivotal studies.
That makes Carver, Schafer and colleagues in Nature Aging more useful than its dry title suggests. They gave aged mice one of four senotherapeutics (the cancer drugs venetoclax and navitoclax, or the plant flavonoids fisetin and luteolin), and the treatments reversed age-related shifts in blood proteins including IL-23R, CCL5 and CA13. In human plasma samples across the lifespan, IL-23R climbed with age. If the D+Q subgroup signal holds up, a blood readout of each person’s senescent-cell burden is the tool the field would need to pick who to treat.
You can’t order that test, because IL-23R hasn’t been validated as a clinical measure. Even a validated test wouldn’t tell anyone whether a drug helps, at what dose, or safely. The tomatidine authors write that “comprehensive toxicological and long-term safety studies remain to be conducted.” Back in 2014, Adams said “we don’t know how many green tomatoes a person would need to eat to get a dose of tomatidine similar to what we gave the mice.” Twelve years and one splashy press release later, I couldn’t find a human trial result that answers him.
I won’t spend a dollar on a tomatidine, fisetin or quercetin capsule sold as an anti-aging senolytic until a trial in people shows it improves something that matters, at a dose someone has proven safe.
Sources
- EMBO Molecular Medicine: Costa et al., Tomatidine is a senotherapeutic compound that improves cognitive function and reduces cellular senescence in aged mice (2026)
- Mayo Clinic via ScienceDaily: Mayo Clinic discovers new ways to fight the zombie cells that drive aging (2026)
- Nature: Martini et al., Mitochondrial metabolism and epigenetic crosstalk drive SASP (2026)
- Nature Communications: Victorelli et al., Mitochondrial RNA cytosolic leakage drives the SASP (2025)
- Nature Medicine: Farr et al., Effects of intermittent senolytic therapy on bone metabolism in postmenopausal women, phase 2 RCT (2024)
- Mayo Clinic via ScienceDaily: dasatinib plus quercetin trial results and disclosures (2024)
- Nature Aging: Carver et al., IL-23R is a senescence-linked circulating and tissue biomarker of aging (2024)
- Unity Biotechnology SEC filing: 12-week results of the UBX0101 Phase 2 knee osteoarthritis study (2020)
- University of Iowa via ScienceDaily: green tomato compound tomatidine and muscle atrophy in mice (2014)