Xiamen Jenny Chemical Technology Company in Xiamen City. Best to contact Olivia Wang. Number (also on WhatsApp) is +86 166 2100 6118. They also have TM5441, but the scientific evidence in favour of TM5614 is slightly more advanced. I would go for TM5614. Happy to join an order as well to get a better rate. You have to negotiate with them for a competitive price.
Another new study on PIA-1:
Silencing the “Clot-and-Age” Protein: A Gene-Silencing Shot That Thins Old Blood and Stretches Lifespan
Analysis of: Ferraresso et al. “Age-associated increases in PAI-1 silenced with siRNA-lipid nanoparticles reduces thrombosis and prolongs lifespan.” Blood (2026), 147(18):2053–2063. doi:10.1182/blood.2025029834 , Published 2026 Apr 30
A single intravenous dose of a liver-targeted siRNA nanoparticle knocks down the pro-clotting, pro-aging protein PAI-1 by ~90% for about 10 days, shrinking blood clots and improving survival in old mice — and repeated dosing extended lifespan by 20% in a fast-aging mouse model.
As we age, a single protein quietly tips our blood toward clotting. Plasminogen activator inhibitor-1 (PAI-1) blocks the body’s own clot-dissolving machinery, and its levels climb steadily across the lifespan — from roughly 21 ng/mL in healthy young adults toward 50 ng/mL in older people. That climb tracks with the diseases of aging: thrombosis, obesity, diabetes, atherosclerosis, and Alzheimer’s. Tellingly, the rare humans born with partial PAI-1 deficiency don’t bleed dangerously, but they do enjoy less cardiovascular disease and, on average, live about 10% longer. PAI-1 has therefore become one of the more intriguing “druggable” levers in geroscience.
The problem has been hitting it. PAI-1 shape-shifts between active, latent, and cleaved forms, frustrating small-molecule and antibody inhibitors, none of which has yet won FDA approval. A team led by Christian Kastrup at the Versiti Blood Research Institute in Milwaukee took a different route: rather than blocking the protein, switch off its production. Borrowing the lipid-nanoparticle (LNP) technology behind the COVID-19 mRNA vaccines and the approved siRNA drug Onpattro, they packaged a small interfering RNA (siPAI-1) that homes to the liver — a primary source of circulating PAI-1 — and degrades its messenger RNA.
The results are striking in their consistency. One shot cut circulating PAI-1 by about 90% in mice, an effect lasting roughly 10 days before fading. Treated blood dissolved clots faster in the test tube, with no sign of impaired normal clotting. In a brutal surgical model of deep-vein thrombosis, treated young mice formed almost no clot, and — most notably — old mice given siPAI-1 survived at 83% versus just 33% of controls. The drug also normalized the sky-high PAI-1 of obese mice, trimmed cholesterol by 14% in atherosclerosis-prone mice, and, given weekly, extended lifespan by 20% in Klotho-deficient “fast-aging” mice.
The big idea is a shift in strategy: instead of chasing a slippery protein with a drug that lasts hours, you silence the gene that makes it for days to weeks, using a delivery platform already proven safe in humans. Six months of weekly dosing produced no detectable toxicity, organ damage, or excess bleeding. The caveats are equally important — these are mouse studies, the lifespan win came in a progeroid model rather than normally aging animals, and the human payoff remains hypothetical. But as a proof of concept that a clinically translatable RNA therapy can durably lower an aging-associated risk factor, it is a notable step.
Actionable Insights
This is a preclinical mouse study; there is no consumer intervention to adopt today. The take-home value is directional — it sharpens why PAI-1 is worth watching as a longevity target — and the effect sizes show why interest is warranted.
The headline magnitudes: a single dose produced ~86–90% knockdown of circulating PAI-1 lasting ~10 days. In old mice subjected to total vena cava ligation, survival rose from 33% to 83% — an absolute risk reduction of 50 percentage points, a relative risk of death of 0.25 (a 75% reduction), and a number-needed-to-treat of just 2. Clot burden in young mice fell ~93% (Cohen’s d ≈ 2.4). In atherosclerosis-prone mice, total cholesterol dropped 14% (287 → 246 mg/dL; d ≈ 1.6) — clinically meaningful, since a ~15% cholesterol reduction is associated with materially lower cardiovascular risk. Weekly dosing extended lifespan 20% in fast-aging mice.
The practical message for the longevity-minded reader: PAI-1 is a measurable blood biomarker that rises with age, obesity, and metabolic disease. Lifestyle factors that lower PAI-1 — weight loss, exercise, and improved insulin sensitivity — are already established and freely available. Asking a physician to include PAI-1 (or its driver, metabolic/visceral-fat status) in a risk panel is reasonable. But siPAI-1 itself is not available, not human-tested, and should not be inferred to be safe or effective in people from this work. [Confidence: High that PAI-1 is a valid aging biomarker; Low that the drug benefits translate to humans.]
Source:
- Lead Institution: Versiti Blood Research Institute, Milwaukee, Wisconsin (corresponding author Christian J. Kastrup). Collaborating institutions include the University of British Columbia (Canada), Medical College of Wisconsin, Michigan State University, and the University of North Carolina at Chapel Hill.
- Country: United States (with Canadian collaboration).
- Journal: Blood (American Society of Hematology).
Impact Evaluation
Blood carries a 2024 Journal Impact Factor of approximately 23.1 (CiteScore ~23, ~96th percentile in hematology). The impact score of this journal is 23.1, evaluated against a typical high-end range of 0–60+ for top general-science and clinical journals; therefore this is a High impact journal