The Hayflick Limit: why humans can't live forever

 A scientific legend, Leonard Hayflick, passed away at the beginning of August. Most non-scientists probably don’t recognize his name, but he made a remarkable discovery in the early 1960s. Back then, while doing experiments on human cells, he and a colleague, Paul Moorhead, discovered that our cells can only divide a limited number of times.

This discovery, although made at the level of an individual cell, has a dramatic implication: humans cannot live forever.

What Hayflick discovered was that after 40 to 60 rounds of splitting in two, cells simply won’t divide any more. At that point, they enter a phase called senescence, and they eventually die. The number of divisions that a cell can go through is now known as the “Hayflick limit.”

Prior to Hayflick’s experiments, many scientists believed that cells could divide forever. After all, every cell in our body comes from one original cell, and that cell came from our parents, and from their parents before that, and so on back through the ages. So it stood to reason that cells could continue to divide without limit. What’s more, in the early 20th century, Alexis Carrel (a Nobel laureate) claimed to have grown cells in his labs that continued to divide for decades, with no sign of decline.

(Aside: Jan Witkowski explained in an article back in 1980 that it was likely that Carrel’s seemingly immortal cells had been quietly replenished, without Carrel’s knowledge, by members of his lab who were eager to keep the boss happy.)

Back to the Hayflick limit: because all of our organs are destined to wear out, our bodies will simply die unless we can intervene and restore cells to their youthful state. That would require technology that has not yet been invented. Hayflick himself estimated that the limit of the human lifespan is 125 years.

Hayflick’s limit raised an intriguing puzzle: how does a tiny, microscopic cell keep track of how many times it has divided? In other words, how can a cell know how old it is? Don’t all of our cells have identical DNA? Hayflick himself didn’t have a solution for this, but a few decades later, others figured it out.

The answer to this cellular “clock” puzzle resides, it turns out, in our DNA. More specifically, it depends on the DNA sequences at the very ends of our chromosomes, which are called telomeres.

Telomeres don’t really do anything, and they appear very simple: they consist of a long stretch of six DNA bases, TTAGGG, repeated hundreds of times, end-to-end. All our chromosomes end with telomeres, on both ends.

So here’s the thing: when a cell divides, it has to copy all of its chromosomes. The mechanism for copying isn’t quite perfect, and it can’t go all the way to the end of the chromosome, so the new copy is a little bit shorter. The telomere gets shorter! Fortunately, we have a special enzyme, called telomerase, that fixes this problem by adding a few extra copies of TTAGGG to the end of each chromosome, restoring the proper length. Problem solved, right?

Well, no. Telomerase doesn’t work perfectly, and chromosomes sometimes do get a bit shorter each time they divide. When the chromosomes get too short, the cell can’t divide any more, and it eventually dies.

And yes, scientists have explored the question of whether telomere length might be the key to longevity. No one has figured out a way to keep telomeres long, and it’s not clear that would help anyway. On the contrary, as my Hopkins colleague Mary Armanios reported in a study last year, long telomeres might help individual cells stick around, but they don’t seem to prevent aging.

Does the Hayflick limit mean we really can’t live forever? Well, not necessarily. Some types of stem cells can produce “fresh” cells that could, in theory, replenish our old cells. Perhaps some day we’ll have the technology to replace our organs with new ones, possibly grown in a lab, that will have the youth and energy of a 20-year-old. But without replacing our parts, we are destined to wear out, even if we manage to avoid cancer, infections, and the many other perils that humans face.

Leonard Hayflick made it to 96, a ripe old age by today’s standards. It would have been fitting if he’d reached 125, the limit that he estimated, but no human has ever done that. Yet.

Does Taurine Really Extend Life? Maybe.

 Readers of this column will know that I’m highly skeptical of dietary supplements. So you might imagine my reaction when I saw headlines a few days ago about “Taurine, the elixir of life?” (at CNN) and “Supplement slows aging in mice and monkeys” (NY Times).

Unlikely, I thought. But I read the scientific article behind these reports, and now I’m intrigued.

What is taurine? And could it really slow down aging? Well, it seems like it could, just maybe. A new study published last week in Science (one of the top journals in all of science) seems to show, for the first time, that taking large doses of taurine, an essential amino acid, might provide a host of benefits that include slowing down the aging process.

First question first: what is taurine? It’s an amino acid, but it’s not one of the 20 amino acids that comprise all the proteins in your body. It’s a slightly different one, and our bodies naturally produce it in small amounts. We need more than our bodies produce when we’re very young, but we get it from breast milk, and it’s added as a supplement to infant formula.

We also get extra taurine from our diet: the best foods for taurine are meats, especially shrimp and other shellfish, but also beef and the dark meat in chicken and turkey.

What did the new Science paper show? Well, first the authors (from Columbia University, India’s National Institute of Immunology, and the Sanger Institute in the UK) describe how taurine levels clearly decline with age in humans and other mammals. Now, just because taurine declines doesn’t mean that replacing it will reverse the aging process, but at least it establishes plausibility.

They then describe a series of experiments, mostly in mice but also in monkeys, where they fed the animals relatively large amounts of taurine each day, and the results were pretty darned impressive:

1. Life span in the mice increased by 10-12%.
2. In mice that started taurine supplements in middle age, life span increased by 18-25%.
3. Bone density increased in female mice and osteoporosis seemed to be cured.
4. Muscle strength increased in both males and females compared to mice who didn’t get taurine.
5. The number of senescent cells–cells that don’t do much except emit damaging inflammatory signals–seemed to be reduced.

Of course, there’s always a big caveat with results in mice: they’re mice, not humans! And many, many times we’ve seen results in mice that just don’t carry over into humans. So the scientists also did a study (a smaller one) in monkeys, which are much closer to humans genetically. This also had some very good results:

1. Bone density increased in the spine and legs.
2. Body fat was lower than it was in monkeys that didn’t get taurine.
3. Several measures of inflammation decreased.

Monkeys live a lot longer than mice, so the scientists don’t yet know if taurine increases the monkeys’ life span, but all the signs are promising. I was skeptical going into this article, but I couldn’t find any obvious flaws.

In an accompanying article in Science, U. Penn’s Joseph McGaunn and Joseph Baur point out that we don’t know for sure what the risks of long-term supplementation with taurine would be, but it is already widely taken as a supplement in baby formula and in energy drinks, with no known ill effects.

However, the amounts used in the Columbia study were very high, much higher than you’d get from energy drinks or even from standard taurine supplements. I looked up a few, and typical formulations offer 1000 or 2000 mg (which is 1-2 grams) per day. The doses given to monkeys in the study, if converted to a 150-pound person, is equivalent to about 5500 mg (5.5 grams) per day. That’s not very much by weight, and it would be easy enough to take this much taurine, but no one knows the effects in humans of such high doses.

The bottom line: this study is really intriguing. More studies are needed, especially to measure the effects of taurine on humans, but all the signs are positive. I’ll be watching closely to see if the effects in mice and monkeys carry over, and if they do, we may all be taking taurine supplements one day. And I just ordered some taurine powder for myself–why not?

Do telomeres measure our true biological age, and can we do anything to maintain them?

Telomeres are one of the keys to aging. We’ve known this for decades, and the scientists who first figured it out won the Nobel Prize in 2009. (One of them was my former colleague at Johns Hopkins University, Carol Greider.) Not surprisingly, many people have been trying, ever since, to use this discovery to slow down or reverse the aging process.

No luck so far, but that doesn’t mean you can’t spend money on your telomeres.

Over the past decade or so, a number of companies have started offering to measure your telomere length, which they suggest will tell your true, biological age. Sometimes, along with these measurements, they will offer to sell you something that they claim maintains or even lengthens your telomeres, thereby making you younger. What’s all the fuss?

Well, let’s start by explaining what telomeres are. Every cell in your body contains your DNA, arranged into 23 pairs of chromosomes. (That’s the origin of the company name for 23andMe, by the way.) Your chromosomes are very long strings of DNA letters (usually written A, C, G, and T). Through a quirk of biology, the very tips of our chromosomes are special: they contain thousands of copies, repeated end-to-end, of the 6-letter sequence TTAGGG. These are the telomeres, and they are a common feature in all animals, plants, and pretty much every living thing except for some single-celled microbes.

What’s fascinating about telomeres is that they provide a molecular “clock” that you can use to tell how old a cell is–sort of. You see, each time your cells divide, they have to copy all of that DNA, and sometimes they don’t quite copy the entire telomere. Over time, your telomeres get shorter.

This means that, in theory at least, your telomere length can tell you something about your age.

When humans are still infants, our telomeres are about 10,000 DNA letters long, and they slowly get shorter. By the time we’re in our 80s and 90s, our telomeres might be only 4000-5000 letters long–but this varies enormously. Telomere length varies from tissue to tissue–even your blood has many different types of cells in it, with different telomere lengths–and from person to person. Thus it’s entirely possible for a healthy 40-year-old to have telomere lengths that are typical of 80-year-olds, and vice versa. Here’s a graph from a scientific study that looked at telomeres in over 800 people, showing how they get shorter as you age. Length is on the vertical axis, measured in thousands, versus age on the horizontal axis:

Part of Figure 1 from “Collapse of telomere homeostasis in hematopoietic cells caused by heterozygous mutations in telomerase genes, G Aubert, GM Baerlocher, I Vulto, SS Poon, & Lansdorp, PLoS Genetics, 2012. © 2012 Aubert et al. This is an open-acce

AUBERT G, BAERLOCHER GM, VULTO I, POON SS, LANSDORP PM (2012) COLLAPSE OF TELOMERE HOMEOSTASIS IN HEMATOPOIETIC CELLS CAUSED BY HETEROZYGOUS MUTATIONS IN TELOMERASE GENES. PLOS GENET 8(5): E1002696.

As you can see, telomeres decline from about 10,000 letters (bases) at birth to about 5,000 in 80-year-olds, but many people have telomeres that are thousands of bases shorter or longer than the average.

When its telomeres get too short, a cell will die. So the reasoning goes, if we can keep our telomeres nice and long, we’ll live longer! It might seem simple, but it’s not.

First, it’s not clear that there’s anything we can do if we know the length of our telomeres. As my Hopkins colleagues Mary Armanios explained, “Within the normal telomere length range, it is not possible to determine a person’s exact biologic age, nor is it a good marker of a person’s ‘youthfulness.’”

The other problem is that it’s not clear that we can take any action to make our telomeres longer, or even to prevent them from getting shorter. But there are a couple of things you can try:

Exercise regularly. There is some evidence that regular exercise is correlated with longer telomeres. A study in 2017 concluded that “adults who participate in high levels of physical activity tend to have longer telomeres, accounting for years of reduced cellular aging compared to their more sedentary counterparts.”

Avoid stress. Another study in 2016 found that stress tended to make telomeres shorter.

Even if both of those studies are wrong about telomeres, the general advice to exercise and avoid stress is good for all sorts of reasons, so I’m happy to endorse these recommendations.

In addition, there are companies (like this one) that claim you can take supplements that will maintain telomere length, but I couldn’t find any solid evidence to back up those claims. So no, you can’t take a supplement or a pill that will restore your telomeres to the lengths they had when you were a baby.

Finally, there is some promising early research that uses mRNA technology–the same technology used to develop the new COVID vaccines–to deliver enzymes that rapidly increase telomere length in human cells. A huge caveat is that this only works in cells growing in a laboratory culture, and no one knows if it’s possible to do this in a living human. But it isn’t a crazy idea, so I’ll keep an eye on this research.

So what about companies that offer to measure your telomere length? Well, they really can do it, although the accuracy of various technologies will vary. Given what we know today, it seems unlikely that these tests will provide anything of value, unless you’re among a very small cohort of people who have a telomere-related genetic disorder. So my advice is, don’t waste your money. But it can’t hurt to exercise regularly and avoid stress, and both of these pieces of advice might help maintain your telomeres as well.

Is this drug combo a true fountain of youth?

Is rejuvenation of the thymus a key to restoring youth? Maybe it is.

A very surprising result appeared last week in a journal called Aging Cell. A team of scientists published the first results of a study that showed, in a small group of older men, that some signs of aging could be reversed with a 3-drug combination.

Not just slowed down. Reversed.

If this holds up, it could literally be life-changing for millions of people. I was initially very skeptical, having read countless claims of anti-aging treatments over the years, virtually all of which turned out to be wrong. Anti-aging treatments are a huge commercial market, full of misleading promises and vague claims. Youth-restoring skin treatments (which don't work) are a particular favorite of cosmetics companies.

But this new study is different. The scientists decided to explore whether recombinant human growth hormone (rhGH) could help to restore the thymus gland. Your thymus is in the middle of your chest, and it is part of your immune system, helping to produce the T cells that fight off infections. As we age, the thymus shrinks and starts to get "clogged with fat," as a news story in Nature put it. Hints that rhGH could help restore the thymus goes back decades, but it had never before been tested in humans.

The scientists leading the study added two more drugs, DHEA and metformin, because rhGH does carry some increased risk of diabetes. Both of these drugs help to prevent diabetes, and both might also have anti-aging benefits, although neither of them is known to affect the thymus.

Amazingly, in 7 out of 9 men in the study (it was a very small study), the thymus showed clear signs of aging reversal, with new thymus tissue replacing fat. The side effects of rhGH are very mild, and none of the men in this study had any significant problems from it or from the other two drugs.

Equally remarkable was another, unanticipated, sign of anti-aging. The study measured "epigenetic age" in all the subjects by four different methods. "Epigenetic age" refers to markers at the cellular level that change as we age, and as the study explains:

"Although epigenetic age does not measure all features of aging and is not synonymous with aging itself, it is the most accurate measure of biological age and age‐related disease risk available today."

After 9 months of treatment, the epigenetic age of the men in this study was 2.5 years younger. The treatment didn't just slow aging–it reversed it. The effects persisted in a followup 6 months later: one and a half years after the study began, the men's epigenetic age was 1.5 years younger than at the beginning. This is truly remarkable.

Any study has limitations, so I should mention a couple here. First, the study was very small, just 9 men, but the effects were strong and significant. Second, the lead scientist of the study, Gregory Fahy, is the co-founder of a company called Intervene Immune that plans to market anti-aging treatments. The authors also include scientists from Stanford, UCLA, and the University of British Columbia.

A few years ago I wrote about another drug combination, dasatinib and quercetin, which showed great promise in reversing aging, but only in mice. We're still waiting to hear more about that treatment, although a test in humans showed some promise earlier this year.

The new 3-drug combination is the most promising I've seen yet. The possible benefits are enormous: as the study points out, they include lower risks for at least 8 types of cancer, heart disease, and stroke. Unlike many other anti-aging treatments, this one has genuine plausibility, and the effects on the thymus can be measured almost immediately. Let's hope this one works out; we'll all be better off if it does.

What's the limit of the human lifespan? And what do World War I veterans have to do with it?

Graph showing lower rate of mortality (blue) in people aged
90-95 versus the rate in people aged 50-55 (orange). Figure
from S.J. Newman (2018) Errors as a primarycause of late-life
mortality deceleration and plateaus. PLoS Biol 16(12):
e2006776. https://doi.org/10.1371/journal.pbio.2006776

An intriguing phenomenon has emerged in recent years: among very old people, the rate at which people die appears to decline when they get past a certain age. In other words, as these authors claimed in their 2011 book, aging slows down and maybe even stops. Or at least the mortality rate levels off past the age of 100, according to another study published earlier this year. This has led some scientists to speculate that the upper limit on human lifespan may be much older than anyone alive today.

Not so fast, says a new study by Saul Newman in PLoS Biology. Newman looked at the data and found something quite different: it's all just a mistake. Well, perhaps not a mistake exactly, but a consequence of many small errors. Let me explain.

In almost all species, mortality rates increase with age. In other words, as you get older, your likelihood of dying in a given year slowly but inexorably increases. Intuitively, we all know this: if young people die, it's tragic because we don't expect it. When people in their eighties and nineties die, it's sad, but no one is really surprised.

The evidence for decreasing mortality among very old humans has emerged from a number of studies that provide seemingly solid evidence that people over 100 die at the same or even lower rates then people between 80 and 90, or between 90 and 100.

Not surprisingly, many people would like to believe that human lifespan is unlimited. Indeed, it's one of the hottest topics in Silicon Valley these days. And perhaps someone will invent some true life-extension technology someday. But Newman's analysis pours cold water on the notion that our natural longevity is unlimited.

One difficulty with studying very old people is that there simply aren't that many of them, so the studies tend to be small. Another problem–and this is what Newman zeroes in on–is that we don't have very good birth records for people over 100 years old. They were born a long time ago, when record keeping wasn't always so good. What if there are a few errors?

It might seem that this shouldn't matter, as long as the errors are random–in other words, as long as people's ages are both under- and over-estimated at the same rates. The problem is that even if the errors are random, they don't play out that way. Here's why.

For the sake of argument, let's imagine a set of people whose true ages are off by 5 years in either direction. (I know that's a lot, but bear with me.) By the age of 100, as Newman points out, virtually no one is alive from the cohort that underestimated their age; these are people who have a true age of 105. But many more will be alive from those who overestimated their age; these are the 95-year-olds who think they're 100.

Newman's paper points out that if only a few people are overestimating their age, this can cause mortality rates to flatten or decelerate–or at least they appear to decelerate, because these people aren't really as old as we (or they) think they are. He then shows, in considerable detail, that only a very small error rate is more than enough to explain all of the apparent decline in mortality rates from recent studies. In other words, the decline in mortality is simply an illusion.

What does World War I have to do with any of this? Newman explains:

"approximately 250,000 youths inflated their ages to enter the 1894–1902 birth cohorts and fight for the United Kingdom in World War I."

The same thing happened in the U.S. and other countries: 16- and 17-year-old boys said they were 18 so they could sign up. Coincidentally, these men would have been around 100 years old when many of the recent studies of centenarians were conducted, and it's very likely that some of these men were included in those studies. It wouldn't take many to distort the apparent mortality rates.

Who could have imagined that these brave young men who signed up to fight for their country (my grandfather was one of them), so many years ago, would have this completely unexpected effect on the science of aging, almost exactly 100 years after the war ended? It seems somehow appropriate that today, as the last veterans of the Great War leave us forever, they can still remind us of their sacrifice.

Did a biotech CEO successfully reverse her own aging process? Maybe not.

Elizabeth Parrish, CEO of BioViva.

Humans have been searching for the fountain of youth for millenia, dating back to ancient times. No one has found it yet, so I was very skeptical when I saw the recent announcement from BioViva, a biotech company, of what they called the first successful gene therapy against human aging:

"Elizabeth Parrish, CEO of Bioviva USA Inc., has become the first human being to be successfully rejuvenated by gene therapy, after her own company's experimental therapies reversed 20 years of normal telomere shortening."

That's quite a dramatic claim. If true, this would be a historic breakthrough: no one has ever reversed aging before. While human life expectancy has doubled over the past 150 years, virtually all of this progress has been from preventing early deaths, thanks to the developments of antibiotics, vaccines, and public health advances such as clean water.

Human life expectancy has doubled since the 1840's.
Figure source: Natl Institute on Aging.

Most claims about anti-aging therapies are easily dismissed as pseudoscience, nonsense, or scams. Not this one, though. BioViva has two experimental therapies, both based on legitimate science, and both with at least a chance of working. Neither has yet been proven to work in humans, but both are plausible.

According to BioViva and to interviews with its CEO, Elizabeth Parrish, Parrish received two therapies last year, one to protect against the loss of muscle mass, and one to lengthen her telomeres. The recent announcement claims that the telomere-lengthening therapy is already working, so I looked a bit deeper to understand what might be going on.

First a bit of background: telomeres are special DNA sequences that act as "caps" on both ends of every chromosome, providing a kind of protection for your genes. Each time a cell divides, its telomeres get a little bit shorter, and eventually they get too short and the cell dies. Telomeres therefore act as a kind of molecular clock that tells a cell how old it is. Our cells also have a special enzyme called telomerase that rebuilds telomeres. Cells with lots of telomerase can live much longer, and those without it die more quickly. Discovering how this all worked was a tremendous scientific achievement, for which Elizabeth Blackburn, Carol Greider, and Jack Szostak received the 2009 Nobel Prize.

Scientists have been speculating for years that telomerase might somehow hold the key to aging. BioViva's gene therapy delivers telomerase to the blood with the help of weakened viruses called adeno-associated viruses (AAVs), which they modified to carry the telomerase gene. The virus infects human cells and releases its payload into them, where the "transgene" produces extra telomerase.

This may sound very nice, but it's really, really complicated in practice. Gene therapy can have unexpected negative effects, and no human trials have yet shown that anyone can deliver telomerase effectively to human cells. However, studies in mice have shown some remarkable results: in 2012, a group of scientists at the Spanish National Cancer Centre used AAV to deliver telomerase to mice, and found that it "had remarkable beneficial effects on health and fitness" and that

"telomerase-treated mice, both at 1-year and 2-years of age, had an increase in median lifespan of 24 and 13%, respectively."

This exciting scientific result, and a few others like it, are what led BioViva and Elizabeth Parrish to try the same therapy in humans.

But did it work? Well, this is where things get a bit fuzzy. BioViva claims it did, based on their measurements of the length of telomeres in Parrish's white blood cells in September 2015, before therapy started, and again in March 2016. They claim that her telomeres got longer, from 6.71 kilobases (a kilobase is 1000 DNA letters) to 7.33 kilobases. This increase corresponds to about 20 years of aging: in other words, Parrish's white blood cells "have become biologically younger," as the company reported.

Setting aside the problem that we cannot really conclude anything from an experiment involving only one person, we can still ask: did Parrish's telomeres really get longer? As much as I want to believe BioViva's claim, there are several rather serious problems here. First, the company itself reported that Parrish's telomeres were unusually short for her age before the experiment began. Does this mean that the measurements were simply a bit off, and the second measurements were closer to the true number? Second, as UCLA's Prof. Rita Effros explained in an interview at geneticexperts.org,

"The overarching problem is that peripheral blood contains a mixture of many different cell types with disparate telomere lengths.... Thus, a simple change in the proportion of different cell types within the peripheral blood could easily explain the data."

In other words, it's possible that Parrish's telomeres did not get any longer. Despite the apparently precise numbers, BioViva has not provided any details showing that these measurements are accurate and reproducible (and they didn't respond to my request for these details). Their claim might be much more convincing if they made multiple measurements, both before and after treatment, and if these measurements showed that Parrish's telomere lengths really did increase.

There are a number of red flags about BioViva itself. Parrish herself is not a scientist, though she is an eloquent spokesperson for her company's therapies. More concerning is their Chief Medical Officer, Jason Williams, who previously ran "a dubious stem cell clinic," Precision StemCell (now located in Mexico) that offers stem cell therapies to patients with ALS (Lou Gehrig's disease), for which there is no evidence that they work. Personally, I would not trust Dr. Williams with my medical care.

The bottom line is that we simply don't know if BioViva's treatment worked on Elizabeth Parrish. They need to produce more data, on more patients, to construct even a mildly convincing scientific argument. Getting more patients may be very difficult, though: Parrish bypassed FDA regulations by traveling outside the U.S. (to Colombia) to conduct this experiment on herself.

Telomerase treatment to reverse aging is very promising, and it might really work, someday. I sincerely hope it will.  For now, though, BioViva's announcement leaves me very skeptical.

A true fountain-of-youth drug combo?

This is really, really interesting. Can we alleviate the effects of aging by getting rid of "bad" cells in the body?

A new study from the Mayo Clinic and the Scripps Research Institute reports that a novel cocktail of two unrelated drugs 

“dramatically slows the aging process—alleviating symptoms of frailty, improving cardiac function and extending a healthy lifespan.” 

The scientists who conducted the study, led by James Kirkland, Laura Niedernhofer, and Paul Robbins, screened 46 different compounds to find ones that would interfere with the ability of senescent cells to survive. The two that seemed to work best were quercetin and dasatinib. They call these drugs "senolytic" for their ability to kill senescent cells.

Old cells are supposed to die and let the body replace them. Most of them do, but some cells become senescent: old geezers who just won’t go away. The problem is, these cells just don’t sit quietly in the living room reading a book. Instead, they make lots of noise, throwing things around that can mess up the living room and make all the other cells miserable. At a molecular level, they secrete enzymes that cause inflammation and other problems, which may explain the relationship between these cells and age-related chronic diseases such as heart disease and osteoporosis. 

This current line of research started about four years ago, when the Mayo Clinic's Jan van Deursen published a study (in mice) showing that if you could selectively destroy senescent cells, the mice had fewer age-related diseases and lived up to 25% longer. Senescent cells, it seems, are definitely a problem.

The challenge is that very few cells are senescent, even in very old people, and it's difficult to destroy these cells without harming all the healthy cells around them. In the new study, Kirkland and his team screened 46 different compounds to find ones that could interfere with what they called “pro-survival” genes in senescent cells. The theory is that the senescent cells have a special ability to survive, and if we can interfere with that ability, the cells will die.

The two compounds they found are very different. Quercetin is a common plant extract, found in a wide variety of fruits and vegetables, especially capers, red onions, plums, and cranberries. Dasatinib, in contrast, is a highly specialized cancer drug made by Bristol-Myers Squibb (NYSE:BMY) and sold under the name Sprycel®. Dasatinib is used to treat CML, a form of leukemia. Quercetin is cheap and easily available, while dasatinib is very expensive and cannot be obtained without a prescription.

The study results were very impressive: after a single dose, mice had improved heart function that lasted up to 7 months. Periodic doses worked too: mice showed improvements in a wide range of age-related symptoms, including bone loss, tremors, grip strength, and overall body condition.

Before everyone runs out and buys a giant bag of red onions (or a quercetin supplement), I should inject a dose of skepticism. Quercetin’s effect on lifespan has been studied before, and it came up short. A study in 2013 by Stephen Spindler and colleagues looked at extracts of blueberry, pomegranate, green tea, black tea, quercetin, and other plants, feeding each of them to mice in a controlled experiment. None of the mice lived longer, and Spindler reported that 

“our results do not support the idea that isolated phytonutrient anti-oxidants and anti-inflammatories are potential longevity therapeutics.”

However, the method of delivery for quercetin and dasatinib in the new experiment was different, and the combination of the two might have benefits that quercetin alone does not offer. As Kirkland point out, dasatinib and quercetin “are both approved for use in humans and appear to be relatively safe,” although they then go on to point out a variety of possible side effects, some of them harmful. They end, though, on a remarkably optimistic note: 

“If senolytic agents can indeed be brought into clinical application, they could be transformative. With intermittent short treatments, it may eventually become feasible to delay, prevent, alleviate, or even reverse multiple chronic diseases and disabilities as a group, instead of one at a time.”

Of course, results in mice often fail when we try them out in humans–but not always. Let’s hope this drug combination shows the same effects in humans that Kirkland and colleagues observed in mice. None of us are getting any younger.

Does a 3-day fast reset your immune system?

I’ve been hearing new reports lately that sound an awful lot like pseudoscience: that fasting for an extended time, two days or longer, can reset your immune system and provide other health benefits. I first heard about this when a friend and colleague at Stanford University announced he was going on a 3-day fast. To explain, he pointed to a recent study, which I’ve now read.

Diet advice, including fasting-based diets, can be found all over the Internet, and much of it is nonsense, so I was very skeptical about these latest claims.

This time, though, there might be something to it. The scientific study that my colleague told me about was published back in June by USC’s Valter Longo, who studies aging and longevity. In this paper, Longo and colleagues described remarkable metabolic changes that occurred as a result of prolonged fasting. They found that fasting for 3 days or longer–drinking only water and eating less than 200 calories per day–can truly “reset” some components of your immune system. 

The research looked at both mice and humans. (It’s far easier to run the experiments in mice, of course, but we can’t always trust that the same effects will occur in humans.) In both species, fasting lowered white blood cell counts, which in turn triggered the immune system to start producing new white blood cells. White blood cells (or lymphocytes) are a key component of your body’s immune system.

Longo’s hypothesis is that fasting (or starvation) forces your body to “recycle a lot of the immune cells that are not needed” which explains the drop in the white blood cell count. Two of the key mechanisms are an enzyme called PKA and a hormone called IGF-1, both of which are reduced by fasting. Once you start eating again, your stem cells kick back into high gear to replenish the cells that were recycled.

The human part of the study was much more limited: a group of cancer patients fasted for 1, 2, or 3 days prior to chemotherapy. The idea is that fasting might reduce the harmful side effects of chemotherapy, particularly the immunosuppression caused by some chemotherapeutic drugs. These results are very preliminary: the patients are participating in a phase I clinical trial, which is designed to assess safety, not effectiveness. Nonetheless, the results indicate that a 3-day fast (but not a 1-day fast) was beneficial for these patients.

A key finding in this research is that you have to fast for several days to get any benefit: basically, you have to fully deplete your energy reserves (in the form of glycogen), and it takes your body at least 24 hours, and probably 48 hours or more, to do this. This is much harder than a 1-day fast, which many people do routinely. 

On the other hand, Valter Longo has compared the effects of periodic fasting to long-term caloric restriction, which has been shown to prolong lifespan in mouse and other animals. In a separate review article, Longo wrote: 

“Fasting has the potential to delay aging and help prevent and treat diseases while minimizing the side effects caused by chronic dietary interventions.”

Caloric restriction is extremely difficult to achieve for humans: you have to nearly starve yourself for years. Compared to this, an occasional 3-day fast should be a snap.

Caveats: fasting can be harmful, especially for people who have other health problems. If you’re seriously thinking of trying this, you should consult your doctor first. And this preliminary evidence, though encouraging, is primarily based on mice, not people. We might eventually learn that the benefits of fasting are outweighed by other problems. Fasting for more than two days isn’t easy, either: you’re going to get really hungry. 

Does a 3-day fast truly reset your immune system? Well, maybe not a total reset, but at least a mild refresh. The science suggests that, if you can do it, a prolonged fast for 2-3 days or longer may induce your body to clean out some old immune cells and switch on production of new ones. Stay tuned.

[An interesting aside: this study was lengthy and complex, and the authors apparently went to great lengths to satisfy the peer reviewers: the paper was submitted in October 2012, re-submitted after revision in December 2013, and finally accepted in April 2014. 18 months is a very long time.]

Can a cosmetic lotion turn back time? Not yet.

A few years ago, L’Oréal introduced two new product lines that used “gene science” to "crack the code" and make your skin young again. The new products were supposed to boost the production of “youth proteins” in your skin, making it look years younger. According to L’Oreal’s ad campaign, the benefits were clinically proven.

Except they weren’t. Last week, the FTC announced that L’Oréal had settled charges that the advertising for these products, Youth Code™ and Lancôme Génifique, was deceptive and misleading.

In a statement, L’Oréal responded that these claims "have not been used for some time now" and "the safety, quality, and effectiveness of the company's products were never in question."

What did L’Oréal claim? Here are some quotes from an ad for Lancôme Génifique:

"At the very origin of your skin's youth: your genes. Genes produce specific proteins. With age, their presence diminishes. Now, boost genes' activity and stimulate the production of youth proteins."

This sounds pretty amazing - and expensive, as much as $132 per bottle for Lancôme Génifique. L’Oréal Youth Code™ makes similar claims: on of its ads asks "Imagine: what if you could grow young?" and then goes on to promise "Even though you can't grow young, we now have the knowledge to help you begin cracking the code to younger acting skin."

The FTC apparently disagrees with L’Oréal's statement that the effectiveness of these cosmetics was not in question. Here is just one claim from a L’Oréal's ad that was highlighted by the FTC:

Génifique Youth Activating Concentrate is clinically proven to produce perfectly luminous skin in 85% of women, astonishingly even skin in 82% of women, and cushiony soft skin in 91% of women, in seven days.

This claim appears in a very scientific-looking bar graph in ad for Lancôme Génifique. It must be science - it's a graph! Alas for L’Oréal, the FTC states that science doesn't support this claims and that it is "false and misleading."

When I asked what studies supported the claim that these products could activate genes, a L’Oréal spokesman pointed me to two published studies, here and here. These are indeed peer-reviewed studies in high-quality journals. However, they don't support the claims made for these skincare products. Instead, they examine which genes are activated when the outer layer of skin is stressed by tape stripping, UV radiation, and washing with detergent. Neither study provides any evidence for a lotion that could activate the same genes, nor do they show that activating those genes could restore skin to its youthful state.

Can skin cream possibly make your skin young again? Well, it's plausible. A baby's skin does behave differently from an adult's skin, and much of that difference may be due to genes being turned on or off. But today, even if we knew the identity of these "youth proteins", we don't have the technology to turn them on.

To their credit, L’Oréal does invest significantly in research, so maybe they will find a youth-restoring cream one day. But not yet.

It's easy to find dramatic claims for products that restore youthful skin. Procter and Gamble's Olay® has many webpages devoted to anti-aging products, and you can be pretty certain that none of them will make you young again either. Like L’Oréal, P&G makes claims about genes:

"That discovery [the human genome] led P&G Beauty Scientists to explore how skin-related genes respond to aging and environmental stress at the molecular level."

As a geneticist myself, I can't help liking the idea that we might somehow convince skin cells to turn on a set of genes to restore their youthful state. Perhaps one of these companies will someday develop a lotion to do this - I hope they will. But they haven't done it yet. So for now, save your money: expensive skin creams are no better than inexpensive ones.