Scientists de-age brains of mice by decades

"Researchers say they may have worked out how to reverse brain aging by decades in a ‘jaw-dropping’ scientific breakthrough.

Scientists at the University of California, San Francisco (UCSF) and the University of Queensland in Australia, found that when given PF4, a protein naturally found in the blood, older mice recovered the sharpness of middle age, and young mice got smarter.

Researchers examined the effects of PH4 on two-year-old mice, equivalent to a 70-year-old human, and said their cognitive function was restored to that of a 30 or 40-year-old." […]


My memory improvement has been off the charts over the past 3 years.

I remember the smallest details like inconsequential people’s names and things from decades ago that I thought I’d forgotten, but they just come back instantly.

I am confident it is the rapamycin and the lowering affect it has on inflammation. Similar to what the PF4 protein is doing.


“PF4, a blood cell made by platelets, can help restore brain function by calming the immune system and stopping inflammation, which leads to aging in the brain and body.”

You could be right: Rapamycin calms the immune system (immunomodulator) and stops inflammation! My memory is also very good.


I hate to get too excited about any one announcement too early on because other scientists often show up and pour cold water of realism on new announcemnts but this sounds VERY COOL.

This really seems to go along with the parabiosis studies really well.

The idea that exercise, increased klotho expression, and parabiosis are all increasing longevity in the same way (PF4) is a pretty fundamental discovery.

Since I’m not going to be getting young blood transfusions any time soon and I already do a decent amount of exercise, I’ve been looking into ways of increasing Klotho expression. There’s a good list over here at SelfHacked. Factors That Increase Klotho (Protein) + Gene Associations - SelfHacked

  • Exercise – in both humans and mice. Klotho only increases post-exercise in people who completed a 16-week training program, with younger people having a bigger increase than older people. Based on mouse studies, it’s believed that muscle injury and new muscle cells secrete Klotho [7].
  • Vitamin D ( Calcitriol) increases Klotho. However, Vitamin D supplements apparently don’t work in humans to increase Klotho, even when calcitriol goes up. In dialysis patients, vitamin D supplements actually decrease Klotho [23, 24, 25, 26].
  • Insulin increases klotho. This is one downside to a really low carb diet [27].
  • PPARgamma activators [12, 28].
  • Activated charcoal by binding to a toxin that decreases klotho (Indoxyl sulfate) [29].
  • Probiotics such as Acidophilus + L Lactis in aging mice [30].
  • Cordyceps reverses the Angiotensin II decrease in klotho [31].
  • Gentian root extract – might simply stabilize some part of the process after its production [32].
  • ACE inhibitors
  • Statins (HMG -CoA reductase inhibitors) – might simply stabilize some part of the process after its production [33, 34, 32].

Makes me happy to see that the Losartan and Rosuvastatin are giving a few extra Klotho promoting benefits.


Lozartan is an ARB, not an ACE inhibitor. Lisinopril is an ACE inhibitor.

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“PF4 actually causes the immune system to look younger, it’s decreasing all of these active pro-aging immune factors, leading to a brain with less inflammation, more plasticity and eventually more cognition,” said Saul Villeda, Ph.D., associate director of the UCSF Bakar Aging Research Institute and the senior author on the paper.

“We’re taking 22-month-old mice, equivalent to a human in their 70s, and PF4 is bringing them back to function close to their late 30s, early 40s,” he added.

Identification of PF4 as a cognitive enhancer shows promise in developing new treatments for brain rejuvenation, although further research is necessary to determine if the findings could be applied to humans.

Papers referenced:

More information: Adam B. Schroer et al, Platelet factors attenuate inflammation and rescue cognition in ageing, Nature (2023). DOI: 10.1038/s41586-023-06436-3.

Park, C. et al. Platelet factors are induced by longevity factor klotho and enhance cognition in young and aging mice, Nature Aging (2023). DOI: 10.1038/s43587-023-00468-0.

Odette Leiter et al, Platelet-derived exerkine CXCL4/platelet factor 4 rejuvenates hippocampal neurogenesis and restores cognitive function in aged mice, Nature Communications (2023). DOI: 10.1038/s41467-023-39873-9

Journal information: Nature Communications , Nature , Nature Aging


True true, but Losartan has been observed upregulating Klotho as well


Would be super interesting if PF4 could become a relatively easy longevity biomarker to keep an eye on


“Scientists uncover how young blood rejuvenates aging brains”
Not sure how glad I am to hear this. This could unleash a Pandora’s Box of social engineering throughout the world, further increasing the distance between the haves and have not’s and empowering dictators everywhere.
Let’s hope this results in discovering other ways than using actual blood. And, sooner rather than later.


Really interesting. I did a very quick search and found this company. Although I don’t know anything about them.

Not sure how far they are along, but it’s good to know that this stuff is being worked on.


Thank you for sharing. Like the self-hack-addict I am, I asked if they have samples or product for sale :joy::joy::joy:


There doesn’t seem to be a lot of activity from them. It’s hard to say where things are with Biotech a lot of companies fail in the early stages. They mentioned going into clinical trials in two years four years back and they haven’t made any updates for a while. That may have folded, but let’s hope not.

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Probably, got no response to my email yet :slightly_frowning_face:

Conboy papers (2020 & 2022) involving plasma dilution in older animals, including humans, both showed positive changes in PF4. It hasn’t been shown yet, but plasma donation (easy to do and free) which involves a smaller volume (about 25% each donation) might influence PF4. My guess is that there’s a dose response curve and that the 50% NBE used by Conboys, and larger exchange during TPE, is not needed to have some overall benefit. Also, not sure if there is an easy to measure proxy for PF4. I do plasma (or platelet) donations approx. monthly and am trying to define & refine blood markers to track (DNA damage etc.) so it’s a work in progress.


does that mean taking low-dose aspirin daily is not a good idea as it does interfere with platelets? @RapAdmin

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I noticed that Peter Diamandis is taking Losartan in his stacks. I was on Losartan then switched to Telmisartan, maybe I should switch back?

Activated charcoal is a solution to upregulate klotho?
This guy has an interesting paper: Factors That Increase Klotho (Protein) + Gene Associations - SelfHacked

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I’m not sold on low dose aspirin… the benefits for healthy people seem pretty minimal and there are some risks. And generally, I try to keep my list of supplements and drugs to the highest impact, highest value (cost/benefit) products - and for me aspirin doesn’t make the cut.

In the ITP trial, the best results came from a single site, so I don’t find that too compelling:

Source: Nordihydroguaiaretic acid and aspirin increase lifespan of genetically heterogeneous male mice - PMC

Recommendation Summary

Population Recommendation Grade
Adults aged 40 to 59 years with a 10% or greater 10-year cardiovascular disease (CVD) risk The decision to initiate low-dose aspirin use for the primary prevention of CVD in adults aged 40 to 59 years who have a 10% or greater 10-year CVD risk should be an individual one. Evidence indicates that the net benefit of aspirin use in this group is small. Persons who are not at increased risk for bleeding and are willing to take low-dose aspirin daily are more likely to benefit. C
Adults 60 years or older The USPSTF recommends against initiating low-dose aspirin use for the primary prevention of CVD in adults 60 years or older. D


Indoxyl sulfate comes from dietary l-tryptophan. This is bad. I’ve been taking l-tryptophan because I thought it would help make NAD and for sleep. I think I might stop even though I don’t have any trouble with my kidneys.

I liked the cordyseps solution.

This also looks like a good reason to be less crazy on vitamin D. Keep it around 50. Am I wrong about this?

Both telmisartan and losartin are angiotensin II receptor blockers.

“Elevated circulating alpha-klotho by angiotensin II receptor blocker losartan is associated with reduction of albuminuria in type 2 diabetic patients”

I suspect if a similar study was made with telmisartan the results would be similar.
Telmisatan is generally regarded as being superior to losartan. That is why I switched to telmisartan.

“Telmisartan has a unique profile among ARBs, with a high affinity for the angiotensin II type 1 receptor, a long duration of receptor binding, a high lipophilicity and a long plasma half life. This leads to sustained and powerful blood pressure lowering when compared with the first marketed ARBs, such as losartan and valsartan.”

Telmisartan: a different angiotensin II receptor blocker protecting a different population? - PubMed.