Quick journal club on IPSC anti-aging paper: cool, but outstanding questions

A new Cell paper from Juan Carlos Izpisua Berlmonte’s group has made headlines about anti-aging across the globe because it suggests that the four core induced pluripotent stem cell (IPSC) factors use by Shinya Yamanaka to make IPSC can reverse aging. I’ve pasted the graphical abstract from the paper below and done a quick journal club style overview based on a quick skim of the paper.


Graphical abstract from Ocampo, et al Cell 2016

Some of the media headlines are rather dramatic on this story. For instance, in a story on it over at STAT the four Yamanaka factors (referred to as 4F: OCT4, SOX2, KLF4, and MYC) are referred to in the title on the new paper as “fountain-of-youth” molecules.

Yeah, I’d say that’s way over the top. But in contrast from my initial look at the paper, I don’t think the authors engaged in hype in the discussion of their results so kudos.

There are a number of reasons to be interested in this paper. It is novel and touches on some exciting areas of science, but I have some sizable questions about it too even just after a quick skim-read of it. A video from the Salk about the studies is below.

The paper used not only both surrogate molecular markers of aging such as DNA damage examined by staining, but also studies of both literal tissue aging and lifespan in mice as outcome measures (which is a lot of work and impressive). They found that pulses of the 4F condition seems to counteract aging, which is particularly evident in mutant mice that prematurely aging. These Progeria mice that received intermittent pulses of 4F exhibited significantly reduced speed of aging. More generally 4F mice also were able to recover from various kinds of injury better.

Just the right ‘Goldilocks’ amount of 4F is needed as the team found that persistent 4F outright kills the mice due to tumors. Since the 4F contains a powerful oncogene called MYC (one of my lab’s favorite proteins), another caveat longer term would be that even mice only given intermittent 4F might be more prone to tumors. However, the team did not report tumors in the intermittent 4F mice so far, which is encouraging.

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No radical life extension, says Nature paper, but Russian gets stem cell infusion to go for it

Any takers on the idea that we can get radical life extension through new technologies like stem cells, organ replacement, cybernetics, or genetic modification? Or just through healthier living in general?

A new Nature paper says there’s a natural limit on human lifespan around age 115 and getting past that is just not going to happen.


Jeanne Calment, who lived to be 122. Photo NY TImes/Getty

They don’t discuss (that I saw on a brief look) how new technologies could break this “rule”. Carl Zimmer has a nice NYT article on this development and on human aging more generally.

It also discusses the curious case of Jeanne Calment (pictured above) who lived to be 122, which the authors of the Nature paper would say was an extreme fluke.

It’s ironic that on the same day I saw all of this about limitations, I also noticed an article (via Google alert on stem cells) in the Russian newspaper Pravda about a scientist there who will get an infusion of stem cells to try to defy aging.

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Muddier stem cell waters: Stemedica teams up with UCSD doc?

stemedicaAn increasing trend in the stem cell arena is the teaming up of clinical partners with very different backgrounds and priorities. For instance, academic institutions are more often working together with for-profit stem cell clinics.

Another branch of this larger trend is the observation that some publicly traded stem cell biotechs such as Bioheart are increasingly turning to non-traditional means of raising cash such as through dubious stem cell training for doctors or other unexpected ventures.

It seems that in the past things were clearer in terms of who is compliant and who isn’t, who is following the spirit of FDA regs and who isn’t, and so forth.

The waters of the stem cell world are getting far muddier today as I predicted in my top 20 predictions for stem cells in 2015.

It’s a somewhat radioactive topic.


On the one hand such team efforts between academic and industry could be beneficial by speeding translation to patients, which is what the field needs. Cheers for that.

However, on the other hand for-profit stem cell clinics and academics do not always see eye to eye on how to do things, how to report findings, bioethics, patient consent, stem cell tourism, the proper way to handle public relations, and such.

Increasingly the commercialization of stem cells is making for strange bedfellows.

A good recent example is the work just announced that Stemedica indicates links it with UC San Diego (UC) for a stem cell trial for Alzheimer’s Disease:

“The study is sponsored by Stemedica International, S.A. and will start at the University of California, San Diego (UCSD) under Principle Investigator Douglas Galasko, M.D. and expand to other sites.”

You may recall Stemedica from the media frenzy over the last half a year on their role in the treatment of hockey legend Gordie Howe for stroke. In fact, Howe reportedly just got a second treatment from Stemedica and its partner Novastem in Mexico.

I found some aspects of the whole Howe-Stemedica story to be of great concern. For example, there is some question over whether the free treatment of Howe has led to stem cell tourism via more patients traveling to Mexico for non-FDA approved interventions. Football great Bart Starr may also have recently gotten such a treatment via Stemedica as well.

Of this new Alzheimer’s trial, Stemedica says in a PR:

“This study was approved based on the excellent safety profile of Stemedica’s cGMP-manufactured, hypoxically-grown stem cells and on solid pre-clinical data obtained by Stemedica International in cooperation with the École Polytechnique Fédérale de Lausanne of Switzerland and with a grant from the Swiss government,” said Lev Verkh, Ph.D. Stemedica’s Chief Regulatory & Clinical Development Officer. He continued “We are very proud of Stemedica’s clinical program under U.S. INDs for several indications including ischemic stroke, acute myocardial infarction, chronic heart failure, cutaneous photoaging and Alzheimer’s disease. At the study’s conclusion we will understand if our approach is efficacious versus placebo in subjects with Alzheimer’s-related dementia, as evidenced by neurologic, functional, and psychiatric endpoints.”

Now in principle some definite good could come from Stemedica working with academics and notably they have an FDA-approved IND for this, which is great. At the same time there may well be different priorities at work. I guess we’ll have to wait and see how it goes.

Other stem cell clinics raise more concerns and claim university affiliations too. For example, earlier this year we saw an odd stem cell clinic with their NIH-like name (National Institutes of Regenerative Medicine; NIRM) turn out to be affiliated with Cell Surgical Network, the largest chain of stem cell clinics in the US, which sells non-FDA approved “therapies”. NIRM had claimed a UCSD affiliation as well, but I no longer see that apparent on their website today.

Notably, Stemedica is different in some key ways from the dubious stem cell clinics we often talk about. They have a growing number of FDA-approved INDs and by all accounts I’ve heard through the grapevine that the stem cells that Stemedica produces are cGMP quality. Still their actions have raised concerns on some levels and the promotion of stem cell tourism to Mexico is a worry.

Overall, as the stem cell waters continue to muddy and with essentially zero apparent regulatory action by the FDA’s CBER specifically on stem cell clinics more broadly in the last couple years, I predict it will be increasingly difficult to know what is going on with any particular stem cell offering. Instead of getting clearer, things are getting grayer.

The cheating death excitation

Who doesn’t want to cheat death?

I know I certainly do.

Cheating deathCan stem cells help many people in the immediate future to escape death (pictured here in personified form as Death t from Wikipedia)?

Recent headlines on new stem cell-related clinical developments would make you think so and they go a step further to indicate that such miracles are just around the corner.

We are all susceptible to such hype.

When it was early days after my diagnosis with prostate cancer in 2009 one of the many doctors that I saw said something that has really stuck with me.

“Our goal is to help you die of something else besides prostate cancer!”

What this doctor said is perfectly right as a goal, but it stunned me a bit at the time.

I don’t want to die of prostate cancer, but I don’t really want to die of anything. However, I will be dying of something eventually whether it is that or something else.

Something will eventually get you too.

It’s just not fun to think about.

Instead it’s a lot more enjoyable and exciting to imagine escaping death through some cutting edge, sci-fi-ish technology like stem cells.

In the last few weeks there’ve been an unusually large number of papers and newspaper headlines about stem cell clinical developments and as much as I hate to say it as an advocate for the stem cell field, many of these cases have been hyped.

The reporters, their headlines and in some cases even some of those involved in the research seemingly would like you to think that cures for all kinds of bad things are about to happen tomorrow. These kinds of pieces often also tend to ignore the often equally important work of scientific competitors as well, which is surely not a good thing.

It can be difficult to sort through to discern what is real hope versus hype and to see the bigger picture where there are many groups doing great things.

There are some words and phrases that tend to crop up that can be clues to what is being hyped in the stem cell headlines: “miraculous”, “cure”,” breakthrough”, and assorted comparisons to once-in-a-century or -millennium kind of events such as landing on a man on the moon or the development of antibiotics. If you see those breathless kind of words, paradoxically you should be less excited and more skeptical.

Stem cell technology will be that important overall and it will make such humanity-changing events come to pass, but we aren’t there yet. It’ll probably take another decade or two to really get closer to being a reality. Raising expectations sky high right now with over-the-top claims and headlines is not helpful to progress. At the same time being an advocate for this work and drumming up interest is important, especially in these days of minimal funding. The key is balance.

So I’d say get excited and talk about the cool stem cell work going on, but also do your homework, give credit to competitors where credit is due, temper your statements a bit, and keep plugging away on the research.

Note: the title of this post was inspired by the titles of Big Bang Theory episodes.

Five simple updated ways to protect your stem cells to stay healthy & younger

Here’s an updated 2013 look at protecting one’s own existing stem cells.

Regenerative medicine is very exciting.

But what’s even better than regenerative medicine?

Preventative medicine.

If one can prevent a problem from occurring in the first place, it is far better than trying to treat it after the fact. Of course in many cases we do not know the causes of diseases so it is difficult to prevent them. However, many diseases are likely caused by problems with stem cells.

Therefore, stem cell research, including the work being done funded by CIRM, is likely to have enormous preventative medicine implications as well.

The average person can do some simple things to protect their and their family’s own population of stem cells and lower their risk of many diseases.

So what can we do?

Don’t get scared, get educated.

Below are some suggestions.

They may sound deceptively simple, but I think they can have a major impact. You’ll note that none of them involve paying thousands of dollars for stem cell infusions. I don’t believe that works. You’ll also note that I do not list taking so-called “stem cell supplements”. Why? Because they almost certainly don’t work.

The main thread running through all 5 suggestions is educating yourself to make little changes that protect your existing stem cells. In turn the stem cells will likely have a better chance to take care of you fixing your injuries, helping you get over illness, and possibly helping you stay a bit younger.

I discuss these kinds of steps for protecting your stem cells and a novel theory of aging based on stem cells in my new book.

1) Lower your risk of skin cancer by protecting your skin stem cells. Become an educated user of sunscreens and about sun exposure. Their use is complex and in fact may be harmful if misused as most of us do.

It seems likely that much or all of skin cancer is the result of UV radiation from the sun damaging skin stem cells. However, it is also recently becoming clear that sunscreens have many potential problems. Their labeling is confusing and it is often unclear just how much protection they afford the user. It is also very concerning that there is growing evidence that some sunscreens may actually increase your risk of cancer either through the chemicals they contain such as Vitamin A derivatives and/or through giving people a false sense of security that they are protected if they don’t burn. There is an excellent article on this including thoughts from several physicians here in the NY Times. It’s important to note that a small amount of sunlight is likely to be healthy by producing Vitamin D in your skin. As it turns out, the majority of people have Vitamin D deficiencies. There has been some very exciting research, including on stem cells, on the importance of Vitamin D for our health. It may be particularly important for preventing cancer, but also other diseases. Whereas research on Vitamins A and E have been disappointing for showing health benefits, research on Vitamin D has proven its benefits and many new studies of Vitamin D are underway. In any case, the best protection from skin cancer is shade or if you have to be out in the sun, clothing. Do not let sunscreen increase your sun exposure dramatically or its use will backfire.

2) Minimize your exposure to plastics, protect all your stem cells. The plastics industry has seen a revolution over the last few decades in their product base such that our lives are filled with products made of or stored in plastics. Unfortunately, the levels of plastics and plastic-related chemicals in our bodies have shot up in parallel. The safety of these plastics is largely unknown, however there is growing evidence that some of the chemicals in the plastics such as Bisphenol-A (see Keep Your Stem Cells Away From BPA)  are dangerous and may increase your risk of cancer. Again, the likely target is stem cells. The plastics industry so far has been very successful in blocking regulation of their products, but that does not mean they are safe and the FDA has expressed growing concern about this issue and Bisphenol-A.

Below left is my guides to plastic use.

Plastics Guide

Some super simple ways to protect yourself include the following: NEVER microwave your food in a plastic container of any kind even if it says it is microwave safe (don’t be deceived–there is no such thing as a microwave safe plastic container), if you want to be really safe, never store your food in a container made of plastic, do not drink water out of plastic bottles, do not let your very young children play with/chew on plastic toys, especially those containing Bisphenol-A. Not only will these steps lower your risk of disease, you also won’t be contributing to the massive pollution of our environment by plastic such as the Texas-sized whirlpool of plastic in the ocean that contains an estimated billion pounds of trash, most of it plastic. Apparently there is another whirlpool of plastic in the Pacific Ocean as well.

We don’t want even microscopic whirlpools or plastic or plastic-related chemicals floating around in us or literally inside of our stem cells, right?

3.) Don’t reprogram your stem cells into cancer: Eat food, not chemicals. A growing trend throughout the world is the consumption of food-like products that are not really food. It’s important to take the simple step of knowing what you are putting in your body. Any packaged food is something you should learn more about before eating. Read the label. Are there many ingredients that sound like chemicals and that you do not know what they are? If so, that’s a bad sign. If they sound like artificial chemicals, that’s what they are. They are not food. The safety of food additives is questionable. Many of these chemicals have no place in our digestive tracks or our bodies. They may alter the epigenetic programming of our stem cells or damage stem cells. As the reprogramming field advances, we are learning the power of chemicals to replace genetic changes in producing iPS cells from skin cells to perhaps one day be used in regenerative medicine. However, chemicals also have the potential to reprogram your normal healthy stem cells into cancer cells.

4.) Exercise your stem cells. No I don’t mean take them out for a walk like a pet. Growing research (see for example here and here) suggests that exercising regularly slows aging and may help maintain a healthier, larger population of stem cells, particularly in the brain, but also in other organs. Exercise is the true fountain of youth and much of its benefit likely stems from stem cells. Of course when we don’t feel well, it’s much harder to exercise, but the point is to do one’s best. Even something as simple as a short walk, gardening, taking the stairs if done almost every day could be helpful.

5) Minimize your exposure to radiation, protecting your stem cells from DNA damage. We have learned in the last couple years or so that many medical tests using radiation have not been administered properly, often exposing patients to enormous doses of radiation. If you need a medical test or are contemplating something like a whole body scan, don’t rush into it if at all possible. Learn as much as you can about the dose of radiation you will receive and the safety protocols in place by those administering the test. Some CT scans, even when performed properly which is what happens almost 100% of the time, deliver the equivalent of up to 500 chest x-rays of radiation.