Anti-Aging in the Media: BBC on Calorie Restriction & Intermittent Fasting

Most of the recent documentaries and newspaper pieces on calorie restriction haven't really offered anything new. They pretty much just repeat the same old arguments about mice eating less and living longer, and then joke that starving yourself will at least make your life seem longer.

This recent BBC Horizon documentary was a positive surprise, however. It does a pretty good job of covering both traditional calorie restriction (CR) and various forms of intermittent fasting (IF), and while the scientists are overly optimistic about either strategy extending maximum lifespan in humans, they do make some good points.

There's for example Luigi Fontana, something of a celebrity in the CR research field, who thinks practicioners of calorie restriction are so much healthier than the average person that they almost "belong to another species". Right. The host of the show correctly points out that Joseph Cordell, the decade-long CR practitioner he interviews, doesn't look remarkably younger than the average 50-year-old.

His blood tests do indicate a very good health, however, and what's interesting is that Cordell is not severely calorie-restricted – he eats 1,900 kcal per day. For an average male, I think that's entirely doable, as long as you pay attention to the nutritional value of the diet to avoid hunger. Cordell also doesn't have that "cancer patient" look to him that a lot of CR skeptics worry about; he's thin but not overly so.

Several of the scientists and professors in the documentary seem to think that intermittent fasting is as good as calorie restriction for longevity, even though the evidence shows otherwise: in animals, IF results in increased lifespan only to the degree that it also results in CR. One of the researchers advocates a diet of fasting and feasting every other day, but not in the traditional 24-hour cycles. Instead, she recommends eating around 400-600 kcal on the fast days and as much as you like on the feast days.

In my experience, at least the 24-hour cycle of fasting and feasting (where you're not allowed any calories during the fast) results in eating twice as much during feast days, unless you purposefully count and restrict calories during feast days as well. She says that there is a calorie deficit, however: during fast days, you're allowed around 25% of your normal calorie intake, and during feasting days you naturally end up eating around 110% of your normal intake. This sounds very strange to me, as it would mean an easy way of accomplishing rather severe CR. I am intrigued by this semi-fasting approach, though.

Another form of IF tried in the documentary is alternate-day feeding based on weekdays instead of 24-hour cycles, i.e. you eat on Monday and then don't eat on Tuesday etc. This is much more difficult than IF based on a 24-hour cycle, since you're essentially fasting around 32 hours at a time. Then there's the 5/2 approach, where you eat for 5 days and then fast for 2 days. And the "4 days of fasting every few months" approach. In the IF circles, there's still debate over which approach is best. Last time I looked, nobody knew the answer to how many hours of fasting is needed to produce the best benefits in humans.

A point that keeps coming up in the documentary is the effect of IGF-1 on aging and the effect of fasting and/or calorie restriction on IGF-1. As Fontana's research suggests, lowering IGF-1 may be crucial for any lifespan extension effects of CR. The 4-day fast clearly lowers IGF-1, but the effect doesn't last long. Cordell's IGF-1 levels are not shown, but since his blood parameters are those of a young man, I assume his IGF-1 is lower than average; probably due to a combination of slight CR and protein restriction.

If you ignore the unrealistic expectations of extending maximum lifespan in humans, the results are overall pretty optimistic. It seems that even a slight reduction in calories and fasting every now and then might significantly improve your health parameters.

Put another way, IF and CR might not make humans live to 120, but they might make you live to 100 without dying of the usual killers like cancer and heart disease. I haven't heard of Joseph Cordell before and am not familiar with how all of his biomarkers look like, but if it is true that he eats 1,900 kcal per day and has only been doing CR since his 40's, perhaps I've underestimated some of the potential benefits of eating only slightly less. Personally, I haven't been doing intermittent fasting for a couple of years now, but I guess it's time to read up on the latest studies and see what's happening out there.

For more information on calorie restriction and intermittent fasting, see these posts:

Antioxidants and Intermittent Fasting – Good For Longevity?
How to Deal With the 5 Most Common Difficulties of Fasting
Alternate-Day Feeding and Weight Loss: Is It the Calories Or the Fasting?
Anti-Aging in the Media: New York Times on Caloric Restriction and Resveratrol

Antioxidants and Intermittent Fasting – Good For Longevity?

Are blueberry antioxidants beneficial for intermittent fasting? (Photo by Simply Bike)

Is it possible to live longer by combining the benefits of intermittent fasting (IF) and plant polyphenols? A new paper claims that taking polyphenol antioxidants during dietary restriction increases the lifespan of mice more than dietary restriction alone. The antioxidants used in the study were blueberry, pomegranate and green tea extracts.

The subject of the paper – "Potentiation of dietary restriction-induced lifespan extension by polyphenols" – is certainly enough grab the attention of anyone interested in life extension. The abstract seems promising too (link). Here's a quote:

Dietary restriction (DR) extends lifespan across multiple species including mouse. Antioxidant plant extracts rich in polyphenols have also been shown to increase lifespan. We hypothesized that polyphenols might potentiate DR-induced lifespan extension. [––] Polyphenol compounds may potentiate IF-induced longevity by minimizing specific components of IF-induced cell stress.

Let's look at these claims in more detail. First off, it's not clear from the abstract what exactly the authors mean by "dietary restriction". The full paper, however, reveals that they use the term to describe pretty much any kind of diet where access to food is limited, including traditional calorie restriction and intermittent fasting.

The longevity confusion

The problem with that opening sentence is that dietary restriction extends lifespan across multiple species only when it equals calorie restriction. That is, you can make a mouse live longer by only feeding every other day, as long as it results in less calories consumed. This is an important distinction, because many people – including longevity scientists – keep propagating the myth that intermittent fasting has the same benefits as calorie restriction. It doesn't. The reason that IF prolongs lifespan in some species is because the animals fail to compensate for the missed calories on their feeding days.

The next sentence is just as problematic. Yes, plant antioxidants have been shown to increase lifespan, but the question is, compared to what? So far, no one has succeeded in exceeding the known maximum lifespan of mice by feeding them antioxidants. Instead, what we see in many studies is that the antioxidant group lives longer than the control group.

The problem is that almost always, neither group lives very long. Poor diets, poor animal husbandry, poor environment – all play a role in how long the animals live. So, in essence, the antioxidants merely make the unhealthy mice a bit healthier. But this is like making a human live 70 years instead of 60 years by giving them some veggies with his daily bread and then claiming that "vegetables extend human lifespan".

Comparing lifespans

That said, there are some interesting figures in the full paper. The graph below shows the survival rates of the three groups; one fed the control diet, the second fed the same diet but only every other day, and the third fed a diet supplemented with polyphenols every other day:

There's a big drop in the survival rate of the control group around 22 months. For the IF groups, the survival curves look a lot better. So how does this compare to the average lifespan of similar mice kept in good laboratory conditions? Here's a graph of age ranges and survivorship of C57BL7/6J mice (the same strain used in this study):

This survival curve is based on a cohort of 150 male and 150 female mice. As you can see, at 28 months half of the mice are still alive. That's about 850 days, which is a pretty normal figure for mean lifespan of this strain of mice in the literature.

Once again, in the antioxidant study the control group dies earlier than is normal. For some reason, half of the mice are dead at 22 months instead of 28 months. One possible reason is the use of a high-fat diet to "mimic the effects of a Western diet", as the authors put it. This seems like a strange idea to me, because a typical Western diet is no more a high-fat diet than it is a high-carbohydrate diet. Furthermore, plenty of humans (myself included) seem to do quite well on a high-fat diet, whereas with mice it's somewhat different.

The survival curve of the IF mice in the first graph is slightly better than that of the normal-fed mice in the second graph. But that is hardly a surprise, given that both the IF group and the IF + antioxidant group had lower body weights than the control group. In other words, the intermittent fasting once again made the mice eat less than the control group, which in turn resulted in a slightly longer lifespan. It's good to keep in mind, however, that with just 10% calorie restriction longer lifespans have been reported in other studies, so the result is not too impressive.

Conclusion

Perhaps the most interesting result is that the IF + antioxidant group lived slightly longer than the IF group. There's no concensus as to whether it's a good idea to combine CR or IF with antioxidants. It may be that plant polyphenols are essential for optimal nutrition and good for activating sirtuins (which play at least some role in longevity), but there is also some evidence suggests that taking antioxidants may interfere with hormesis and thus diminish the effects of CR.

In this study, the antioxidants had a beneficial effect. While the IF diet by itself activated pro-inflammatory pathways, adding plant polyphenols to the diet blocked this effect. The authors identified 20 gene sets that were down-regulated by the addition of polyphenols, most of them related to immune response, inflammation, cell differentation and tumorigenesis. 

This suggests that if you're doing intermittent fasting, adding some blueberries, pomegranates and green tea to your diet may not be such a bad idea. Note, however, than the mice did not have access to polyphenols during their fasting days, so this study tells us nothing about taking antioxidants during fasting. It also doesn't say much about how polyphenols affect regular calorie restriction without IF in humans.

For more information on intermittent fasting and longevity, see these posts:

Lithium in Drinking Water May Lead to Longer Life
Does Intermittent Fasting Increase Lifespan?
Alternate-Day Feeding and Weight Loss: Is It the Calories Or the Fasting?
Slowing Down Aging with Intermittent Protein Restriction

Guest Post: Natural Alternatives for Arthritis Treatment

Glucosamine is also found in seashells. (Photo by DavidRPhoto)

Guest post by Emily Matthews

Glucosamine sulfate and chondroitin sulfate have long been used as supplements to ease the pain of arthritis. Both compounds are found naturally in animal cartilage and glucosamine can also be found in seashells. A person who wishes to increase the amount of glucosamine and chondroitin in their diet should take them together as supplements, but only from a reputable manufacturer of vitamins and supplements. Medical professionals are uncertain as to the dosage for the average person.

Chondroitin

Chondroitin is a more complex molecule than glucosamine. It's made up of intact or hydrolyzed glycosaminoglycans with attached sugar molecules. Studies from masters degree programs show that it’s not as effective as glucosamine in treating arthritis, as the body doesn’t absorb as much of it; chondroitin is such a large molecule that it's difficult to pass through the normal intestinal barrier. The benefit of chondroitin comes because at least some of it can be broken down into glucosamine in the digestive track.

Glucosamine

Glucosamine is a simple molecule made up of glucose and an amine, which is a building lock of protein. The main effect of glucosamine is to stimulate the creation of glycosaminoglycans, which helps cartilage remain spongelike and act as a cushion between joints. As some people age, their bodies lose the ability to manufacture glucosamine and so the cushioning effect of cartilage is lost. Some studies claim that glucosamine supplements are more effective than placebos or non-steroidal anti-inflammatory drugs in easing arthritis pain

GAIT Trials

In a recent study, the National Center for Complementary and Alternative Medicine conducted the Glucosamine Chondroitin Arthritis Intervention Trial, or GAIT to see if glucosamine and chondroitin sulfate gave any benefits in the treatment of arthritis of the knee. The study was conducted to see if the supplements, used alone or separately, eased the pain of 1583 sufferers of this form of arthritis.

In GAIT, the people who participated in the double blind trial took glucosamine alone, chondroitin sulfate alone, the two supplements together, the prescription drug celecoxib, or a placebo. The results of the trial were that celecoxib significantly reduced the pain of knee arthritis and that glucosamine and chondroitin, taken alone or separately, were no better than the placebo in reducing pain. However, there was a small group of participants with what they described as "moderate to severe pain" who found that the glucosamine and chondroitin sulfate combination reduced their pain significantly.

The efficacy of glucosamine and chondroitin in treating arthritis is uncertain. Glucosamine seems to provide some relief for some arthritis sufferers. Chondroitin is too large a molecule to be absorbed by the body in any appreciable amount. If the glucosamine and chondroitin combination works for some people, it’s probably because enough chondroitin is broken down to increase the effect of the glucosamine.

Emily Matthews is currently applying to masters degree programs across the U.S., and loves to read about new research into health care, gender issues, and literature. She lives and writes in Seattle, Washington.

For more information on glucosamine, chondroitin and arthritis, see these posts:

Green Tea Protects Cartilage from Arthritis in Vitro
Green Tea Protects from Arthritis in Rats
MSM + Chondroitin + Glucosamine for Hair & Nail Growth - Results after Seven Weeks
MSM + Chondroitin + Glucosamine: A Sulfur Cocktail for Hair and Nails

Lithium in Drinking Water May Lead to Longer Life

Water may have an effect on your longevity. (Photo by anthony_goto)

Lithium is an essential trace element found mostly in drinking water and vegetables. However, nutritional intake of lithium varies considerably, depending on where you live.

In rats, a deficiency of lithium causes health problems such as behavioral abnormalities, but in humans, lithium deficiency is an unknown concept. On the other hand, there have been studies suggesting that  lithium intake, even at low doses, is inversely correlated with suicide risk. High-dose lithium has been used for decades to treat psychiatric conditions such as bipolar disorder.

Lithium may also have other life-extending properties besides reducing suicide risk. For example, roundworms have been shown to live up to 36% longer when given lithium chloride, but the amounts used are 1000-fold higher than would be obtainable through diet. Such a high dose may not be necessary, however. In a recent paper roundworms were shown to live longer when given a low concentration of lithium chloride throughout their life – with the effect being less pronounced than with high doses (link).

The authors also looked at lithium in drinking water and total mortality in 18 neighboring Japanese municipalities. They found that tap water levels of lithium were inversely associated with overall mortality adjusted for age and gender. Since lithium levels have been associated with lower suicide rates, the authors also adjusted for suicide. The inverse association between lithium and overall mortality remained.

Lithium concentrations in drinking water ranged from 0.7 to 59 mcg/L. The highest value equals a concentration of 8.5 micromoles. A lithium concentration of 10 micromoles was enough to extend the lifespan of roundworms, while a concetration of 1 micromole was not.

The inverse association between mortality and lithium in drinking water obviously does not prove that lithium reduces mortality in humans, but the roundworm experiments show that the idea is not so far-fetched. Although the mechanism is still unknown, I wonder if the mental health aspect has something to do with it.

Too bad there doesn't appear to be any lithium in the tap water where I live, or at least they don't report it. It is also available as a supplement, but some countries may have customs restrictions on some or all forms lithium.

For more information on longevity, see these posts:

High HDL Cholesterol Reduces Risk of Dying in Men
Selegiline and Lifespan Extension
Does Intermittent Fasting Increase Lifespan?
The 7 Types of Aging Damage That End up Killing You

High HDL Cholesterol Reduces Risk of Dying in Men

Strawberry margarita – the perfect longevity drink. (Photo by bookgrl)

According to conventional wisdom, LDL is the "bad cholesterol" and HDL is the "good cholesterol". While there is plenty of evidence showing this is an oversimplification, it is generally agreed that the higher your HDL is, the better. In fact, I've never seen anyone suggest a "maximum" HDL level for a healthy person.

One of the many strange things you hear most doctors recommend is that you reduce your total cholesterol once it's above a certain level, despite what your LDL and HDL are. That is, even if HDL makes up most of your total cholesterol, you may still get a warning that your total cholesterol is "too high". But why would you want to reduce your HDL cholesterol?

High HDL is generally believed to be associated with longevity, at least to a degree. For example, centenarians and supercentenarians tend to have higher HDL than the general population. To my knowledge, large population studies on HDL and longevity are relatively rare, however – which is why I found this new paper from the American Journal of Cardiology pretty interesting (link).

The study (which began in 1979) looked at the probability of 652 men, aged 65 years, to reach 85 years of age. The authors hypothesized that men with higher HDL cholesterol levels in middle age would be less likely to die before 85 years of age than men with lower HDL levels.

For the analysis, participants were categorized into three groups based on their HDL cholesterol: <40, 40–50 and >50 mg/dL. Converted to mmol/L, the ranges are <1, 1–1.3 and >1.3 mmol/L. To me, these categories seem like they're in the lower range of the healthy spectrum, but then again, average HDL levels in men in the US are said to be 40-50 mg/dL. According to the American Medical Association, less than 40 mg/dL is undesirable and higher than 60 mg/dL is desirable.

The age-adjusted hazard ratios for death before 85 years of age in the three groups were as follows:  1.00 for those with HDL < 40 mg/dL, 0.99 for those with HDL between 40–50 mg/dL, and 0.77 in those with HDL > 50 mg/dL. In the fully adjusted model (which accounted for age, LDL, hypertension, smoking, BMI, etc), the hazard ratios were 1.00, 1.01 and 0.72, respectively. That is, men with HDL higher than 50 mg/dL had a ~28% lower risk of dying than those with HDL lower than 50 mg/dL.

Immediately we can see that it doesn't make much difference whether the participants' HDL was below 40 or between 40 and 50 mg/dL – the risk of dying before 85 years of age was pretty much the same for both groups. Only once their HDL cholesterol levels were above 50 mg/dL was there a significantly lower risk.

Furthermore, when the authors analyzed the data further, they found that each 10-mg/dL increment in HDL cholesterol was associated with a 14% decrease in risk of dying before 85 years of age. In other words, the higher their HDL, the higher the survival rate.

This is all very good news. Reaching a HDL level of, say, 80 mg/dL (~2.1 mmol/L) is not at all impossible as long as you plan your diet properly, and would give you a significantly lower risk of dying from cardiovascular disease – which is the number one killer in the 65–85 age group.

The baseline characteristics of the participants reveal some interesting things too. First, the LDL cholesterol was pretty much the same in all groups: around 160–168 mg/dL. Body mass index, on the other hand, was inversely correlated with HDL levels: those with the lowest HDL levels had a mean BMI of 27.5, while those with the highest HDL levels had a mean BMI of 25.8.

While alcohol is known to increase triglycerides in the short term, it also increases HDL. Indeed, alcohol consumption was positively correlated with HDL levels. The percentage of participants who drank at least 2 alcoholic beverages per day was ~14% in those with the lowest HDL, ~18% in those with average HDL and ~38% in those with the highest HDL. This might explain, in part, why moderate alcohol consumption is associated with increased longevity.

So, if your total cholesterol is high and it's mostly due to high LDL, that may be a potential cause for worry – although it's good to keep in mind that there are several types of LDL, some more harmful than others. However, if you have high cholesterol due to high HDL, well then you should be happy!

For more information on HDL cholesterol and how to increase it, see these posts:

Hibiscus Tea Increases HDL, Lowers LDL and Triglycerides
Refined vs Red Palm Oil and Cholesterol
What a "Heart-Healthy" Diet Does to Your Cholesterol Levels
Anthocyanins from Berries Increase HDL and Lower LDL

Nootropics, Longevity and More: The Year 2010 in Review

Comments or suggestions for the year 2011? Drop a comment! (Photo by Altus)

Happy New Year everyone! I hope your holidays went well and you're ready to make 2011 even better than last year. But before we do that, let's take a look at some of the best bits and pieces from 2010.

In January, I finally got a chance to see Aubrey de Grey for the first time. His presentation in Helsinki, Finland was mostly familiar to me already, but I enjoyed it nonetheless. Perhaps the most interesting part was when the audience got to ask questions; I thought Aubrey's answers were good, especially given that some of the comments were pretty frustrating (apparently some people think going through their entire family history somehow qualifies as a question). If you want to check out the presentation, the video is still available online through the link above. And in case you want to know more about Aubrey himself, he was also interviewed in Wired.com a while ago.

Nootropics are gaining more and more attention these days. Even 60 minutes ran a segment on students boosting brain power to do better in their studies. Amphetamine derivatives are still the most popular choice – but whoever comes up with an "organic herbal formula" that actually works as well as Adderrall is going to be rich. I also did an experiment with Ashwagandha to see whether it had a nootropic effect. It didn't, at least not the brand I was using.

And then there was the experiment with BioSil, the stuff that is supposed to make your hair and nails stronger. The science seems solid, but as I wrote in my conclusion, the price of the liquid supplement doesn't seem worth it, since orthosilicic acid, the active ingredient, is also present in my favourite beverage.

Speaking of hair, a lot of people have asked for an update on the soy isoflavones + capsaicin experiment, another one of my attempts at finding a magical hair growth formula that will make me filthy rich. The experiment has been going on for six months now, which is longer than the five months that the original study lasted, so perhaps a proper update is indeed due. So far I haven't seen much visible changes, however. I'm now adding various kinds of chili powders and pastes to almost all my foods, but I'm thinking of ordering capsaicin supplements to be sure I'm getting enough to match the study. And I also need another bottle of soy isoflavones.

I've tried a lot of useless supplements and topicals, but last year I came across something that really, actually works: retinoids. I've now been using them for over a year and I can really see the difference. My advice to anyone looking for real results is to forget about all the overpriced skin creams that are really nothing but moisturizers and go for tretinoin instead. Of course, since it actually works it's prescription stuff, so you can't just buy it from the store, you'll have to order it online and hope your package doesn't get confiscated by the customs officers who surely know better what you need than you do. Thank god for regulations!

Probably the longest and most throrough post of last year was about human hibernation and how it might relate to longevity. In addition to a look at the current state of hibernation science, there's also the odd legend of lotska, the art of hibernation allegedly practiced by poor Russian peasants:

At the first fall of snow the whole family gathers round the stove, lies down, ceases to wrestle with the problems of human existence, and quietly goes to sleep. Once a day every one wakes up to eat a piece of hard bread, of which an amount sufficient to last six months has providently been baked in the previous autumn. When the bread has been washed down with a draught of water, everyone goes to sleep again. The members of the family take it in turn to watch and keep the fire alight.

And of course, no post on slowing down metabolism would be complete without Indian fakirs and frozen mountain climbers. Check it out if you have the time, it's fascinating stuff.

While the Russian peasants may have spent most of their winter sleeping to avoid starving, there are also those who can eat as much as they like and still avoid getting fat. Even without any exercise. I'll let other bloggers fight it out over the details of the energy equation and whether a calorie truly is a calorie, but take a look at the BBC documentary in the link to see what I mean. Also check out the comment section, some interesting anecdotes in there.

How is the life extension movement doing these days? Well, the same old (and false) arguments against longer lifespans are still there, but the overall mood is pretty optimistic. Personally, I've noticed that younger people tend to be more open to the possibility of life extension than middle-aged people. Go figure. Meanwhile, the Russians have apparently found the cure for aging, although I haven't heard anything new on SkQ1 since September. But that's okay, because the next fountain of youth is already here.

Long-time readers of this blog probably remember that I did intermittent fasting for over a year. Part of the reason was that I wanted to see if 24-hour fasts could be done – I wanted to be the master of my hunger, so to speak. However, the most important reason were the studies showing positive effects from intermittent fasting without restricting total calories. You know, the whole "cleaning cells from junk through autophagy" thing.

But alas, after going through the studies more carefully, I was disappointed to find out that whenever intermittent fasting increased lifespan in mice, total calories had also been restricted. In effect, intermittent fasting extends lifespan only in conjuction with caloric restriction. Some of the other benefits of fasting may still be valid, to a degree at least, but without potential gains in lifespan, I don't see the point in doing a strict 24/24-hour cycle of fasting and feasting anymore. Besides, I now think that even full-blown calorie restriction would only give me a few extra years. Why? Because humans just can't do CR the same way rodents can. More on this later. Meanwhile, see my updated health regimen.

Of course, there were also several other posts which I didn't mention here; see the archives section in case you missed them. And just so you don't miss anything interesting in the future, remember to subscribe to my feed and to follow me on Twitter, which I use to post stuff (life extension, health, science) I don't have time to blog about in depth. Oh yeah, and tell your friends to do so too!

For summaries of previous years, see these posts:

10 Human Experiments of 2009 – Year in Review
7 Human Experiments of 2008 – Year in Review

World's Oldest Woman and Oldest Man: 1986–2010

I came across this graph while browsing through the latest issue of Rejuvenation Research. The black line shows the age of the oldest living woman; the grey line shows the age of the oldest living man. The data spans from 1986 to 2010.

A couple of things pop out from this graph. First, during the last 24 years, the oldest person in the world has always been a woman. Not a big surprise there, since women live longer in general. Quite a few men have gotten past 112 years, but reaching 116 seems impossible. For female supercentenarians, reaching 114 is relatively common, and a few have even reached 116.

The second thing that catches the eye is the highest point on the graph: that's Jeanne Calment, who died in 1997 at the age of 122, making her the longest-living person ever in the world. No one else has reached even 121. Shigechiyo Izumi is missing from the graph – he was claimed to have died at the age of 120, but according to the authors, he was in fact 15 years younger.

Looks like there's a slight trend towards longer-living supercentenarians, but I'm not sure it's significant. Certainly we haven't seen anyone like Jeanne Calment in over a decade. What this graph doesn't tell us, of course, is whether the percentage of people who reach 110 years of age has changed significantly during the same time period.

For more information on aging and longevity, see these posts:

Jumping Head First into the Fountain of Youth
Aubrey de Grey Interview in Wired.com
Russian Scientist Claims to Have Found Cure for Aging
The 7 Types of Aging Damage That End up Killing You

Jumping Head First into the Fountain of Youth

Go on, it'll knock 50 years right off your age. (Photo by JB London)

I don't know if you noticed, but yesterday a study on telomeres and aging hit the news big time. Various media bought into the hype, claiming that aging had been reversed in mice. Daily Mail, for example, published a story that begins as follows (link):

Have they found the elixir of eternal youth? Scientists reverse the ageing process in landmark trial

The secret of eternal youth has been unlocked by scientists in remarkable research that paves the way for a ‘forever young’ drug. Lives could be longer and healthier, free from illnesses such as Alzheimer’s and heart disease, with skin and hair retaining its youthful lustre. Such a drug might allow men and women to have children naturally until they are a ripe old age.

The secret of eternal youth, huh? And just in case you missed what that would be like, the writer states:

The experiments mirror the plot of the film The Curious Case of Benjamin Button, where the lead character played by Brad Pitt ages in reverse.

Except, of course, that Brad Pitt was born as an old man and eventually turned into a fetus and died, which is not exactly the kind of eternal youth I'm looking for. As you might guess, the paper and its authors are slightly less modest about the results – but only slightly. Professor Ronald DePinho, who did the mouse experiments, says:

In human terms, it would be like having a 40-year-old person who looked 80-plus and reversing the effects to the levels of a 50-year-old.

Reporters obviously love statements like this, but the truth behind the hype is somewhat different. First, mice are not humans, so drawing conclusions about what results from mice would mean "in human terms" without actually replicating the experiments in humans can be misleading.

Second, and more importantly, the mice were not normal mice: they were genetically modified to have no telomerase – which, in simple terms, lengthens telomeres – resulting in prematurely short telomeres and thus premature aging. The authors then gave the mice a drug that kickstarted telomerase, and lo and behold, many of the signs of premature aging began to reverse.

Thus, this is very far from giving the same drug to a healthy person and making them live forever. The rejuvenation in this case applies to the damage caused by having artificially short telomeres, not to all the other kinds of damage that comes with aging. This is precisely why the mice given the drug "become normal", so to speak, but were not rejuvenated in the sense that the whole "fountain of youth" metaphor might suggest.

If this were truly a fountain of youth, the mouse would have lived exceptionally long – but they didn't. They lived as long as normal mice.

While I'm glad that the attitude of the media towards life extension seems to be positive and even optimistic these days, the people writing these articles don't seem to have much grasp of reality when it comes to anti-aging science. I don't claim to be an expert, but even a quick glance at the abstract of the paper (link) would have shown that this is not only "ten years away from being available for sale", it's simply not directly applicable to healthy people.

What I found encouraging, however, was that the mice given the drug not only stopped accumulating more damage, but that their organs did indeed begin to rejuvenate. I say encouraging because it shows that aging damage can be repaired and not only slowed down – which is a crucial difference, because for most of us alive today to make it past 120, it will have to be repaired and not just halted.

Another positive thing about the study is that the mice whose telomerase was reactivated did not get cancer. Since one of the purposes of telomere shortening is said to prevent harmful mutations from spreading, many people worry that boosting telomerase may increase the risk of cancer. It would be interesting to see what the same drug does to normal mice.

For more information on anti-aging and rejuvenation, see these posts:

Aubrey de Grey Interview in Wired.com
Russian Scientist Claims to Have Found Cure for Aging
How Do People Feel about Life Extension?
Anti-Aging in the Media: The Independent on Immortality

Aubrey de Grey Interview in Wired.com

Aubrey de Grey's life extension diet emphasizes the importance of beer.

One of my favourite people in the world, the British gerontologist Aubrey de Grey, recently did an interview with Wired Science (link). If you've read his interviews before, you pretty much know what to expect, but there were a couple of new things in there that I found interesting (he's swearing, for one thing).

The gist of Aubrey de Grey's work is keeping people healthy indefinitely. You can call this unlimited healthspans or radical life extension or rejuvenation therapies or whatever, but the idea remains the same: to cure the biological process of progressive deterioration known as aging. For most people, the word "immortality" still has something of a negative connotation. This has not gone unnoticed by de Grey:

I’ve been out there represented as an immortality merchant since forever. These days, I can afford to not just acquiesce and let journalists use phrases like “immortality,” or at least not in the title of the bloody ass thing.

The reason he doesn't like titles like "Aubrey de Grey is here to make you immortal" is because it makes biogerontology sound like science fiction; something that a handful of people are working on in their garage. The public is apparently not ready for immortality.

And yet there are a growing number of people in the world who are ready to live longer and healthier lives. To any reasonable person, the word "immortality" is a positive thing, as long as one understands what the concept of biological immortality means. What it doesn't mean is that you'll be hurling through space long after the earth has been destroyed in a nuclear war, unable to die. It also doesn't mean that you'll be able to survive getting hit by a truck (although if it did, that would be a positive thing too).

What biological immortality means is that the chronological progress of time no longer dictates when and how you die. Your health will no longer be a simple function of time. Your body will remain youthful and vigorous regardless of how old you are. You can still die – certainly so if you want to die for some reason – but it won't be because of your body deteriorating every year. How this is a bad thing to some people has been beyond me for quite some time now.

The first step in solving the problem of aging will be done in mice. From there on, says Aubrey de Grey, it'll be smooth sailing:

What’s going to happen is the curmudgeons — the card-carrying gerontologists who think it’s very dangerous to be over-optimistic — will eventually recognize the data available to us from mice is so solid we can go out publicly and say, “It’s only a matter of time.” That’s going to take a panel of interventions in mice that’s so comprehensive we actually add two whole years to the lifespan of mice that are already in middle age before we start.

That may be overcautious. We may be able to get gerontologists on board with a more modest result than that. However, at that point, game over. My job will be done. I can retire. Because that will be the point when Oprah will be all over it and the following day it will become impossible to get elected unless you have a manifesto commitment to have a war on aging.

I agree with de Grey. People like Oprah have such a big influence on public opinion that it's ridiculous. I can even imagine someone being very pro-aging before hearing someone like Oprah promoting it, and then changing their mind completely. Once you get the public behind the idea, you'll get the politicians as well. Not that I give a damn about influencing politicians – without all the bureacracy and regulations in the field of medicine, I bet we'd already made a much larger progress in rejuvenation therapies! I'd rather take care of my own health than put it in the hands of any government official.

Another crucial point about people like Oprah: they have a lot of money. And since people with lots of money tend to be interested in preserving their wealth, it makes sense that the same people are also interested in preserving their health. After all, what's the point of having billions of dollars if you're not going to be around to enjoy them?

One thing that de Grey has not really commented on before is how come he doesn't get massive donations from aging billionaires. Some of them have already made plans to cryopreserve themselves, but if you have the chance to stick around without spending five decades in an ice box, why not do that instead? The biggest reason seems to be that billionaires haven't taken the organizations seriously enough:

Wired.com: For most of the billionaire philanthropists that travel in the same circles you do, out of the three things, is it mainly that they just don’t like your organization?

de Grey: I think for a very large, a very sufficient proportion of such people, yes, it’s that third thing. Because I see these people a lot. I go to TED, and there’s no holding back when it comes to 1) the desirability of the goal, and 2) the demonstration of sufficient comprehension of what I’m talking about to understand they believe the plan is feasible. So yes, absolutely.

In other words, there's a lack of professionalism, not necessarily in what the organizations actually do but in how people view them. The Methuselah Foundation is a case in point:

In the beginning, the only thing the Methuselah Foundation did was the longevity prizes for mice. Then, we started funding research directly. We thought it was a really cool idea to have one organization with two very complementary approaches to the same mission. But in fact, it didn’t really work, especially not in terms of messaging.

The foundation has now been split into two, one for prizes and one for funding research. Hopefully this will attract more investors. Besides business and funding, Aubrey talks about some personal things as well. And his love of beer, of course:

I drink exactly the right amount of beer evidently. [laughs] It’s ridiculous, really. Yet, I have to show I’m enjoying my life. It’s public knowledge I am polyamorous as well. That’s something that goes down not so well with some of my more politically sensitive friends and colleagues. But it goes quite well with some other people. [laughs]

Polyamorous, huh? He even goes to say that the whole monogamy thing is "archaic" and will probably be a thing of the past some time in the future. I didn't know de Grey was against monogamy, but I happen to agree. I think the whole concept of jealousy is an unnecessary biological impulse that was useful in the past but will no longer be needed in the future. It certainly isn't a product of the rational side of the brain.

I guess contrarians tend to have a lot in common. When you start to question the official truth in one area, you begin to wonder about other obvious truths as well. I'm sure you've noticed the disproportionate amount of libertarians among the paleo crowd, for example. In many cases it boils down to questioning whether government really knows best.

For some reason, the paleo community is still mostly stuck in the "aging is good" dogma, however. They're determinately against diabetes, obesity, cancer, cardiovascular disease, and every other modern plague, and yet they are unwilling to strike the problem at the root.

Basically, they want to live healthy for 80 years and drop dead. To me that's nonsensical. What's your opinion?

For more information on longevity and aging, see these posts:

Russian Scientist Claims to Have Found Cure for Aging
How Do People Feel about Life Extension?
Aubrey de Grey in Helsinki, Finland
Why Aging Is a Global Disaster That Needs to Be Solved

Russian Scientist Claims to Have Found Cure for Aging

Could there really be one pill that keeps you young indefinitely?

This news recently hit the media (link), and the headlines so far have been pretty wild. Catchphrases like "forever young" and "secret to eternal life" will surely spark interest even among the non-immortalist crowd, but how much of it is just hype?

So what is this news all about? The drug in question is the work of professor Vladimir Skulachev, who has dedicated his life to study (and solve) aging. Now he's finally found an antioxidant with anti-aging properties and plans to start selling it in just a few years.

Despite what supplement salesmen will tell you, antioxidants by themselves are not worth much in terms of extending lifespan. In fact, the whole "free radical theory of aging" was put to rest a long time ago. Yes,  antioxidants extend the lifespan of simple organisms, but they've repeatedly failed in mice and rats, and there's no evidence that antioxidants would make humans live longer.

There's a pretty simple reason for that, too: normal antioxidants don't reach the mitochondria where most of the free radical damage occurs. No matter how much vitamin C pills you pop or how many acai berry shots you down, you won't be making any difference in the rate of mitochondrial damage.

It appears that Skulachev has synthesized a mitochondrially targeted antioxidant. There's no detailed information in the article, but based on the papers Skulachev's group has published in the past, it looks like the compound in question is SkQ1, an antioxidant attached to a positively charged ion. Experiments have shown that SkQ1 prolongs the lifespan of a variety of species, including mice (link, link).

Clinical trials on humans are underway, and if everything goes smoothly, the drug will be out in a few years. After successful results from animal studies using eye drops, Skulachev tried it on his own cataract. After six months, his cataract was gone.

So what's the catch here? Well, looking at the lifespan data from mice, they're not talking about an increase in maximum lifespan but in median lifespan. The oldest mice receiving the drug did not live longer than the oldest mice in the control group, they just had a squared mortality curve. In other words, the mice that got SkQ1 made it to old age more often than the control mice.

In humans, this would translate to something like being relatively healthy at 90 years old but still dying around 100 years of age. There's no evidence that you could live to be 150 by taking SkQ1. Thus, claiming that "the cure for aging" has been found or that the "fountain of youth" is finally here is just plain wrong.

Aside from the reality check, this is still very good news. Even squaring the curve would be a fantastic thing in humans – if it works in humans. That would mean that a lot of the diseases associated with aging would be postponed significantly and old people would enjoy a better quality of life.

And, for those of us trying to stay as healthy as possible while waiting on true rejuvenation therapies, drugs like this would be warmly welcome.

For more information on aging and longevity, see these posts:

Selegiline and Lifespan Extension
Does Intermittent Fasting Increase Lifespan?
The Curious Case of Human Hibernation
How Do People Feel about Life Extension?

Selegiline and Lifespan Extension

Deprenyl increases the lifespan of female hamsters. (Photo by MarinaAvila)

Selegiline, also known as deprenyl, is an old life extension drug. It's been around since the 80's, but after some conflicting data from Parkinson's Disease studies, interest in selegiline for life extension purposes has been negligible.

These days, deprenyl is mostly used to treat Parkinson's Disease, depression and dementia. Still, the early studies showed such promising results that a review of the studies on deprenyl and longevity is in order.

Deprenyl extends maximum lifespan in male rats

In the first study on selegiline and lifespan, 24-month old male Wistar-Logan rats were treated subcutaneously with selegiline (0.25 mg/kg) or saline solution three times a week (link). The control group receiving only saline had an average lifespan of 147 weeks, about 34 months. The longest living rat in this group was 164 weeks (~37 months) old.

The deprenyl group did significantly better. In fact, even the shortest living rat receiving selegiline managed to outlive the longest living in the control group, making it to 171 weeks (~39 months). The longest living rat survived for a whopping 226 weeks (~52 months). That's a maximum lifespan increase of 38%. The average lifespan in the deprenyl group was 198 weeks (~46 months). The author, Dr. Joseph Knoll, states:

The average lifespan was higher than the estimated maximum age of death in the rat (182 weeks). This is the first instance that by the aid of a well-aimed medication members of a species lived beyond the known lifespan maximum.

In 1994, Dr. Knoll continued his experiments, again using the same dosing but this time on younger Wistar-Logan rats (28 weeks, or ~6 months old), some of which were sexually inactive and some of which were sexually highly active (link).

The sexually inactive control rats remained inactive throughout their life and lived 135 weeks (~31 months), whereas their deprenyl-treated peers suddenly developed a hunger for sex and lived 152 weeks (~35 months), the same as the sexually active control group. The highly active rats given deprenyl became even more sexually active than their saline-treated control group, and lived for 185 weeks (~43 months).

Only mean lifespan increases in another strain of rats

Between Knoll's experiments on male Wistar-Logan rats, another lifespan experiment on selegiline was done. This time, male Fischer rats were given deprenyl (0.25 mg/kg) or saline subcutaneously every other day, starting at 23 to 25 months of age (link).

Again, the deprenyl group lived longer, but this time the effect was not as dramatic as in the previous study. The remaining life expectancy of rats given selegiline was increased by only 16%. Then again, as Ben Best points out in his good summary of deprenyl, Fischer rats live only 28 months, much shorter than Wistar-Logan rats.

In 1993, Japanese scientists doubled the standard dose of deprenyl and injected male Fischer rats with 0.5 mg/kg, starting from the age of 18 months (link). The abstract states:

The increases in average life expectancies caused by deprenyl treatment (15% from 18 months and 34% from 24 months) were both statistically significant.

I don't have access to the full paper, so I'm not sure what exactly they mean by this. Were there actually two treated groups, with one given deprenyl since 18 months and the other since 24 months of age, or did the control group start dropping dead faster after 24 months?

In any case, maximum lifespan was apparently not increased, unlike in the previous studies. A possible explanation is the shorter lifespan of Fischer rats and the higher dose used. On the other hand, Ben Best says on his website:

At the 2004 American Aging Association Conference Kitani (one of the authors of the Fischer study) reported that he had halved the dose to the standard 0.25mg/kg (3 times per week) and increased mean life span 44% for females and 32% for females starting from 24 months. Nonetheless, no significant increase in maximum lifespan was seen.

If the above is correct, then the higher dose is probably not the culprit. Perhaps treatment has to be begun earlier, or perhaps deprenyl doesn't work in all rat strains.

Different doses and forms of deprenyl

In 1992, two more studies appeared in a Hungarian journal, with Dr. Knoll as the coauthor in both of them. The first one fed male mice either deprenyl, Dinh lang root extract or a combination of the two three times a week, starting at 12 months of age (link). The abstract states only that the combination was the most potent treatment, increasing both memory function and survival time.

The second study used the same dosage of deprenyl as before, but this time 6-month old male Wistar rats and a different form of deprenyl known as (-)p-fluoro-deprenyl were used (link). The study lasted for 25 months. Three of the 20 control rats (15%) and 15 of the 40 deprenyl-treated rats (37.5%) survived until the end. Three of the rats receiving selegiline were still sexually active at 31 months, even though normal male Wistar rats lose their ability to ejaculate by the time they're 2 years old.

The authors also experimented with a much smaller dose of selegiline, giving 13-month old non-copulator rats only 0.01 mg/kg instead of the usual 0.25 mg/kg. The lifespan of these rats was short, with the control group living only 102 weeks (~23 months) and the (-)p-fluoro-deprenyl group living 106 weeks (~24 months). Rats given the standard deprenyl lived for 104 weeks. Sexual performance was improved in both deprenyl groups, however.

Deprenyl in females, mice, and dogs

The first study on selegeline and life extension on female rats came a few years later. Once again, the dosing was 0.25 mg/kg injected three times a week (link). The rats were 6 months old and had their ovaries removed. All the control females were dead before hitting 15 months of age, while all of the deprenyl-treated rats were still alive. Three of them even reached 36 months of age. Unlike in the case of males, however, neither group showed much sexual activity.

In Syrian hamsters, a low dose of selegiline increased the lifespan of females but not males, even though MAO-B was inhibited in both groups by the same amount (link). Female controls died younger than male controls, but in the deprenyl group this difference disappeared.

Deprenyl seems to increase lifespan also in immunosuppressed mice. When 4 mg of selegiline was mixed in 10 kg of feed, survival improved dramatically (link). The last mouse in the control group died 2.5 months after the study was started, at the age of 5 months, whereas the last mouse in the selegiline group made it to 14.5 months.

Deprenyl and dogs

Rodents are not the only animals that seem to gain extra years from selegiline. A study on beagle dogs, ranging in age from 2.8 to 16.4 years, studied the effects of orally administered deprenyl on lifespan (link). The dose was 1 mg/kg, four times as high as the one originally used by Dr. Knoll on rats.

The study lasted for 2 years and 10 weeks. Almost all of the young dogs survived until the end of the study, but older dogs given deprenyl survived longer than those that were given placebo. 80% of dogs in the deprenyl group survived until the end of the study, compared to only 39% in the placebo group. The first deprenyl-treated dog died on day 247, whereas the first untreated dog died on day 295.

Summary

In the experiments of Dr. Knoll, who first discovered its life-extending properties, selegiline consistently increased the mean and maximum lifespan of male Wistar-Logan rats. The rats given deprenyl had a maximum lifespan that was up to 38% greater than that of the control rats. The longest living rat in these studies was 52 months old. Only one study looked at female rats and life extension, but it too showed an increased lifespan from deprenyl.

Extrapolating directly from rats, the 0.25 mg/kg dose used in the experiments would correspond to 20 mg of selegiline every other day, or 10 mg daily, for a man weighing 80 kg (~176 pounds). For a female weighing 60 kg (~132 pounds), the equivalent would be 7.5 mg daily.

Not all of the results have been so uniformly positive, however. While mean lifespan was increased in male Fischer rats, maximum lifespan was not. One possible reason is the shorter average lifespan of Fischer rats, but other explanations cannot be ruled out. Also, male Syrian hamsters given deprenyl did not live longer, although females did.

For more information on life extension, see these posts:

Does Intermittent Fasting Increase Lifespan?
How Do People Feel about Life Extension?
Dietary Supplement Increases Lifespan by 11% in Healthy Mice
Slowing Down Aging with Intermittent Protein Restriction

Does Intermittent Fasting Increase Lifespan?

Some say feasting and fasting will keep you younger. (Photo by bowtoo)

I often hear or read that intermittent fasting has all of the same benefits of calorie restriction. The idea is that by not eating every now and then while keeping total calories the same you would enjoy the same health effects as you'd get from simply eating less. Including living longer.

This mantra is repeated even in scientific papers, but is it correct? It's certainly easy to see the appeal: since actual calorie restriction means you're counting every calorie and going hungry for most of the time, intermittent fasting seems like a fantastic choice. Besides, the concept does make sense on the surface. Deprive your body of energy for a while, let autophagy do its work, and live longer. It seems to work for fruit flies and worms, after all, so why not humans?

Because humans are more complex. While simple species like roundworms can be very useful for screening life extension therapies, they are no guarantee that the same therapies work in humans. There are a million ways to extend lifespan in roundworms and fruit flies, but much less in rodents, and even less in humans.

Unfortunately, it looks like intermittent fasting (IF) is one of these cases. For obvious reasons, we don't have lifespan studies on IF in humans, but what we do have is studies on rats and mice. And, despite what the popular belief is, the data is much less promising than one might hope. The rather disappointing conclusion of the studies seems to be that intermittent fasting without caloric restriction does not extend lifespan. When it is accompanied by caloric restriction (CR), it does extend lifespan – and it looks like the degree of life extension is highly dependent on the degree of CR.

The reason you see studies showing increased longevity from IF in the first place is because most rodents eat less when they fast every other day. While humans generally compensate for a fast by eating twice as much the next day, mice and rats generally don't. They do eat more, but not twice as much – which means they are calorie restricted.

Don't believe me? Let's take a look at all the studies on intermittent fasting and longevity in mammals. Note that I've skipped all the alternate-day feeding studies that have not looked at lifespans. There are a lot of papers showing other kinds of health benefits from fasting (some of which are also a result of CR!) , and I'm not saying fasting is not healthy in general, just that it does not seem to extend life.

A critical look at the studies

The first paper I could find on the subject is from 1945 (link), not too long after the positive effect of calorie restriction on lifespan was discovered. This paper briefly mentions an even earlier study from 1934, in which mice fasted for two days in a row each week. The average lifespan of the fasted mice was slightly longer than those of controls, but the difference was not statistically significant. There is no mention of weight and food intake.

In the 1945 study, male and female Wistar rats were put on various versions of intermittent fasting. The rats fasted either one day in four, one day in three, or every other day. Fasting was begun at the age of 42 days and was continued until the rats died.

With the exception of females fasted once every four days, the average lifespans of all fasted rats exceeded that of the controls. The increase in lifespan was slightly greater in males than in females, although females still outlived males in general. In male rats, the most effective method was fasting every other day, while in females fasting once every three days gave the best results on average. However, both the male and female rat that lived the longest (1057 and 1073 days, respectively) were fasted every other day.

Food intake was not measured, but since the intermittently fasted rats weighed less than the control rats, we can assume that they also ate less. No drastic retardation of growth was seen, however. So, the first available study on intermittent fasting shows that when rats are intermittently fasted, they don't compensate for all the missed calories on the ad libitum days, and thus are CR'd, and therefore live longer. No big surprise there.

After this study, there was a gap of four decades before similar experiments were done again. During the 80's and 90's, three papers on intermittent fasting and lifespan were published by the same team. In the first one, male Wistar rats were fed either ad libitum or every other day since weaning (link). The mean lifespan of the fasted rats was 83% greater than that of the control group. And, just like in the 1945 study, fasting resulted in a lower body weight. The abstract doesn't mention the exact weights, but since the fasted rats took 75% longer to become fully grown, it looks like they ended up eating significantly less.

In the second paper, male Wistar rats were again fed ad libitum or every other day since weaning (link). This time they were also allowed voluntary exercise. The fasted rats exercised less in their youth but more when they were older. They also lived longer and weighed less than the control rats. However, in contrast to the first study, their growth duration was the same while growth rate decreased. That is, it looks like in the first study both groups eventually grew to the same size, while in the second study the IF rats remained smaller.

The third paper looked at the longevity effect of intermittent fasting (every other day) on three strains of mice, beginning at various ages (link). In two of the strains, mean and maximum lifespan increased and body weight decreased. The A/J strain, on the other hand, showed different results. When intermittent fasting was begun at 1.5 months, the mice lived longer despite not weighing less. When it was begun at 10 months, they again weighed the same as controls but actually died earlier. The rats that began fasting at 6 months weighed less than controls at some ages but showed no difference in lifespan.

Conclusion

In summary, it looks like intermittent fasting extends lifespan in rats and mice only when it is accompanied by calorie restriction. It does not mean that the animals are also put on CR; rather, they just naturally end up eating less (unlike humans, who tend to be very flexible and good at compensating for calories). And, in the rare cases that the animals actually do eat twice as much the next day, their lifespans are not increased.

For those who are doing IF for other reasons than life extension – such as improving insulin sensitivity or ">weight loss – this is not necessarily a concern. While some of the other health benefits reported in the studies are probably a result of calorie restriction, just like lifespan increases, I suspect IF even without CR still has some benefits in humans. It's just that based on the rodent studies, those benefits won't be enough to make us live longer.

For more information on diet and longevity, see these posts:

Dietary Supplement Increases Lifespan by 11% in Healthy Mice
Slowing Down Aging with Intermittent Protein Restriction
How to Live Forever: My 5 Steps to Immortality
Intermittent Fasting Reduces Mitochondrial Damage and Lymphoma Incidence in Aged Mice

My Current Health Regimen v2.0

One of the changes has been an increased intake of fruit and vegetables. (Photo by YimHafiz)

This is my updated health regimen, aimed at adding a significant number of healthy years to my expected lifespan. As it's subject to change, I will keep this post updated accordingly. Major revisions (such as v2.0) will appear once a year or so; minor changes (such as v2.1) will be made as needed. With every major revision, I will move the post from the archives to the front page.

Since a long, healthy life is preferable to a short life by most people, following the regimen would make sense even without considering technological innovations. The true goal of my regimen, however, is to stay alive long enough to see rejuvenation therapies become a reality. In the long run, each year that I'm able to add to my expected lifespan now through things like dietary changes, exercise, and supplements, may grant me several extra years in the future.

Therefore, even those lifestyle changes that require considerable effort and resources while offering a seemingly limited benefit, make sense if one looks at the big picture. For a chance to see the world in 2090, I'm willing to skip the cheeseburger today.

My health regimen consists of four categories: diet, supplements, physical exercise, and brain health. All of the items under each category have some kind of scientific basis, and in contrast to my ongoing experiments, will remain a part of the regimen for the time being. Therefore, my current experiments are not a part of my long-term health regimen – unless they prove to be beneficial, in which case they'll be moved from ongoing experiments to the regimen.

Main changes from v1.0: none.

Avoiding harmful foods

The most important part of my diet is avoiding unhealthy things; increasing the intake of healthy things only comes in second. This is because preventing damage from happening in the first place is easier than repairing it later on.

I consider the worst culprit of modern diets to be an emphasis on grain products, fructose, and polyunsaturated fatty acids. There's considerable evidence to suggest that most people would do much better without them. Hence, things like pasta, rice, bread, candy, fruit juices, and most vegetable oils are off the daily menu. I only eat them rarely, and then simply because they taste good. For the past few months, I've allowed myself to eat whatever I want once a week (usually foods like pizza or fresh bread), which seems to be working well.

I originally cut back on my fruit intake, which used to be quite high some years ago, because I learned that fructose increases triglycerides especially in men, and fructose is not handled very well by the body in general. I later learned that fructose also forms AGEs much more rapidly than glucose, which kept me from reintroducing most fruits to my diet and eat berries instead, since they contain more nutrients per fructose calorie. However, I've now increased even my fruit intake a little, having read more about the AGE-inhibiting effects of phytonutrients found in fruit. I will expand on this later, but for an example of what I'm talking about, see my post about carotenoids inhibiting lipid peroxidation.

While much of this fits well with paleo dieting, I also diverge from the paleo diet these days. You may or may not remember that I used to be a potato hater back in the day, both because they could not be eaten raw (making them anti-paleolithic) and because of their high carb content. Basically, potatoes are just empty calories. But once you have your insulin sensitivity and blood glucose under control, I don't think a few potatoes now and then is much of a concern. At least they're low in fructose.

As you may recall, I followed a low-carb diet for the past year with an emphasis on paleo foods. I got on the low-carb, high-fat wagon in the first place to prove that eating a diet high in fat does not make you fat – and it didn't. However, this diet combined with my year-long intermittent fasting experiment resulted in a moderate-to-high intake of protein, the longevity effect of which I'm now questioning. To lower my protein intake slightly means eating either more fat or more carbohydrates, and since my fat intake is already very high, I've reintroduced some carbs into my diet. That is, I now occasionally eat potatoes not because I think they are necessary for health, but because they are low in protein. More on protein and longevity in future posts.

I still don't make nuts a dietary staple, because of their poor omega-3/omega-6 ratio and because I like to keep my PUFA intake low. That is, I aim not only for a good ratio of omega-3 and omega-6 fatty acids, I try not to eat too much of them in general. Omega-3 is particularly prone to undergo lipid peroxidation, and while nuts probably have micronutrients that protect them from oxidation to some degree, I'm playing it safe until I learn more.

Main changes from v1.0: slightly increased carb intake, slightly decreased protein intake, slightly decreased polyunsaturated fatty acid intake.

Eating healthy foods

Despite eating some more carbs these days, my diet is still fairly low in carbohydrates. My daily intake used to be around 100 grams; I have not measured my current intake, but I suspect it's around 100-150 grams these days. My main protein sources used to be meat, fish and eggs, but during the past year I've cut back on eating eggs because of their high methionine content. I'm still figuring out whether methionine restriction makes sense in humans, but in the meantime I limit my egg intake to 3-4 eggs a week.

Sources of fat, in the order of importance, are olive oil, palm oil, butter, cocoa butter, coconut milk, ghee, coconut oil, and sesame oil. Olive oil tops the list because I love the taste and because it's high in MUFAs but low in PUFAs and consistently does well in just about every health study. There may not be anything magical about MUFAs per se, but even if it's the polyphenols in olive oil that are behind all the positive health effects, olive oil still seems like a good choice. Palm oil is there because it's rich in tocotrienols (at least compared to other natural foods), low in PUFAs and high in SAs (making it suitable for heating), and because I've grown to like the taste.

Lard is off the menu for now because I ran out. Heavy cream has been replaced by coconut milk, partly because of dairy products increasing IGF-1, which may be bad for longevity (more on that in future posts). I don't eat cocoa butter raw (although I could, it's delicious), but I get plenty from all the dark chocolate I eat. Somebody asked me in the comment section why I eat sesame oil since it contains quite a bit of PUFAs, and noticing this was indeed so, I was going to remove it from my diet altogether. However, doing some reading I found that sesame oil seems to reduce markers of lipid peroxidation, so I kept it on the menu. I just use it for taste, however, so my intake of sesame oil is very low anyway.

Depending on my daily menu, anywhere between 50 to 70% of my total calorie intake is from fat. My daily menu has changed a bit, but percentage of fat is still the same. Most of this is saturated fat, which has been given a bad rep for reasons I believe are incorrect. I began reducing grain products and increasing my saturated fat intake years ago, and it hasn't killed me yet. In fact, my HDL has increased and my LDL has decreased on this diet. Triglycerides are not bad but could be better – a testament to my main vices, beer and wine.

There is one cereal grain I regularly eat, however: rolled oats. They're a convenient source of beta-glucan, which appears to be good for cholesterol and avoiding heart disease, and they don't contain gluten. Oats also contain quite a bit of quality protein. I used to eat them with milk and berries, but then switched to a combination of heavy cream and water to reduce my consumption of lactose and galactose (which easily form advanced glycation endproducts, AGEs). Now, I've stopped adding even heavy cream, because milk protein seems to interfact with the polyphenols in berries. So it's a mixture of coconut milk and water nowadays – not as good as cold milk, but still pretty good.

As for red meat, despite how it's portrayed in the media these days, I'm not convinced that meat consumption is harmful. Indeed, a recent review supports the hypothesis that processed meat, not meat in itself, may be harmful. The biggest problem I used to see with meat is the generation of AGEs. Though there is disagreement just how harmful consuming AGEs with food are, I tried to minimize the potential damage by avoiding overcooking and taking supplements. I no longer think AGEs in meat are a huge problem, however – more on this later. The reason I don't eat huge portions of meat like I used to is because of the high protein content.

And finally, the beverage department. I still love my daily coffee, which I drink 1-2 cups per day. Coffee has some nice health benefits too. Green tea is obviously staying on the menu; the studies showing positive health effects just keep on piling up. All in all, beer doesn't really belong to the "eating healthy foods" category, but even beer does contain some good stuff.

As you may recall, I used to drink yerba mate with meals to reduce the formation of AGEs. It's since come to my attention that yerba mate is carcinogenic at higher doses, so I now drink it only rarely. Green tea or black tea are safer bets, despite somewhat contradictory results in reducing AGEs and ALEs.

Main changes from v1.0: decreased egg intake, changes in the use of fats and oils, reduced yerba mate consumption, avoidance of lipid peroxidation.

A note on diet tweaking

It's much easier to point out things that are wrong in various foods than it is to prove something is healthy. These days, I'm more wary of advertising my diet as the best choice for everyone than I was before. Part of the reason is that the more I read and learn about nutrition, the more complicated everything becomes.

Case in point: I used to tell people vegetables are bad because, as an evolutionary strategy, they produce toxins to protect them from being eaten (which is true). Now, having learned of the importance of hormesis, I think vegetables are good because of those same toxins! I was also a huge fan of eating fruit (especially organic fruit) at one point, because it seemed to make sense from an evolutionary point of view. The, I got a little skeptical towards them because of their fructose content. Now, I think the benefits may outweigh the negatives.

All this, however, doesn't stop me from wanting to find the optimal diet for longevity. On the contrary, it's a healthy reminder not to get too emotionally attached to my health regimen, and to be ready to admit mistakes and make alterations as I learn more.

Going without food

The third key component of my diet used to be intermittent fasting. I stated in the first version of this post that "I may change my mind in the future, but for now I expect periodic food deprivation to remain in the regimen." That is still true to some degree: I no longer do a 24/24 hour cycle of fasting and eating, but I don't make it a point to eat three meals with snacks a day either. I often skip breakfast and lunch and eat only dinner.

The thing that lured me to try intermittent fasting was that there are studies suggesting that all or most of the benefits of chronic calorie reduction can be had by alternating zero calories with double the normal calories every 24 hours. While I no longer believe that IF is equivalent to CR, I do think that fasting in general is beneficial. An improved insulin sensitivity is a known result of intermittent fasting. Insulin sensitivity is associated with longevity, and among supercentenarians, insulin sensitivity is common.

Perhaps a more interesting thing about fasting is that it increases autophagy, a process in which the cell consumes a part of itself for energy. This can happen during ordinary cell maintenance, or when the body is deprived of nutrients. Since improved autophagy is at least in part why caloric restriction works, this makes other, less demanding forms of nutrient deprivation attractive options.

The reason I stopped doing strict IF is because I don't think there is much evidence that fasting for 24 hours and then eating for 24 hours is somehow optimal in itself. Most importantly, IF does not extend lifespan in most studies. Why IF is not equivalent to CR is not clear, but recent studies suggest protein may have a lot to do with it. My intermittent fasting diet resulted in huge meals with lots of protein, and I now suspect that this may have diminished much of the potential benefits.

Main changes from v1.0: no more 24/24 intermittent fasting, no more huge protein-heavy meals.

Supplements

The most important supplement in my regimen is vitamin D3. Most people are deficient in vitamin D, and the health benefits are so overwhelming that if there's one supplement I would recommend spending money on, it's vitamin D3. I usually take 5,000 IU of vitamin D3 daily, and at last check, my levels were at 45 ng/mL, which is in the optimal range. Now that it's summer, I'm taking 2,500 IU daily. I know some people take the same amount all year round, but since I do spend some time in the sun, I don't want to overdo it.

One of the supplements that has remained in the regimen since last time is vitamin K2, which is sort of a newcomer in the supplement scene but nonetheless has some impressive studies behind it. I'll write more about it in the future, but here's one study of interest for men: dietary vitamin K2 may reduce prostate cancer. Since fermented dairy products, which I'm not sure are the best choice for health otherwise, are the best dietary source of vitamin K2, I'm taking supplements instead. At the moment, I take 90 mcg of MK-7 (Jarrow MK-7) and 5 mg of MK-4 (Carlson Labs Vitamin K2) every third day in an attempt to find a balance between affordability and the long serum half-life of vitamin K2.

I used to take a tablespoon of fish liver oil daily, because it has lots of omega-3 fatty acids in bioavailable form (EPA and DHA) and almost no omega-6 fatty acids. A higher dietary ratio of omega-3 to omega-6 seems to be very beneficial in general, and fish oil has been shown to decrease inflammation. A commonly quoted optimal ratio is between 1:1 and 1:4, which seems to be close to how our paleolithic ancestors ate. As part of my plan to avoid excess PUFAs, I've dropped fish liver oil from the menu. I'm currently in the process of weighing the pros and the cons; it may be that a tablespoon per day will prove to be worth it in the end.

I also used to take resveratrol with quercetin during fasts to increase autophagy. I would still continue to take them, but unfortunately I can't afford all the supplements I might like to take (including AOR Ortho-Core, which is off the list for the time being), so I take resveratrol only occasionally. Meanwhile, I'm on the lookout for other things that increase autophagy. Curcumin is a cheap alternative, and it has other health benefits too, which is why I add turmeric to most of my foods.

Since my damn blender keeps leaking from the bottom, I'm no longer making smoothies every day like I used to. So these days I just add some ground flax seeds to my rolled oats for the flax lignans. Flax lignans may prevent hair loss, among other health benefits. Some people prefer to take them in supplement form, but flaxmeal is a cheaper and equally effective way to consume flax lignans. For best effects, they should be consumed twice a day with ~12 hours in between. Other things I do to prevent hair loss is use shampoos with ketoconazole and piroctone olamine.

Main changes from v1.0: no more fish liver oil, some supplement cutbacks due to costs, increased curcumin intake.

Exercise

My exercise routine is probably the weakest part of my regimen, compared to how much effort I put into diet and supplements. In the summer, I run for 30-45 minutes once a week to get some aerobic exercise (I should start again, since summer is here!) The goal is to keep the heart and lungs healthy, reduce blood pressure, and improve mood. In the winter, when it gets too cold for running outside, I go to the gym for strength training instead. Strength training reduces the risk of injury, prevents osteoporosis, supports joint health, and prevents muscle loss resulting from aging.

I also practice martial arts, which combines aerobic and strength training, to a degree. The main reason for me, however, is that it provides me with a basic set of self-defense skills and improves coordination. With aging, there is usually an increased fear of falling and hurting oneself – something children naturally don't have. Getting thrown around every week is a way to maintain a healthier attitude towards my body and prevent an irrational fear of getting hurt. I want my mind to rule over my body, not the other way around.

Main changes from v1.0: none.

Brain training

Any anti-aging regime should also take into account the importance of maintaining mental health. It doesn't take a genius to see that people who use their brains actively retain their cognitive abilities far longer than those who are passive.

One of the ways I keep the rational side of my brain fit is reading scientific papers and writing about them on this blog. I like logical problems in general, and I think practicing problem-solving skills are important for everyone, whether it's through work or hobbies. To train the creative side, I do things like play instruments, compose music, and read and write fiction.

My biggest problem is and always has been rather poor short-term memory. I don't know whether it's because my mind is always occupied with a zillion things, but it's more than once that I've gone to the grocery store to buy something I need and come back with something else entirely. This kind of absent-mindedness seems to run in the family. I believe it can be improved through training, however. The memory game experiment intends to increase IQ, but it improves short-term memory as well (I've pretty much forgotten about this experiment lately, by the way – I'll have to start playing again!)

Main changes from v1.0: none.

Quick summary of the health regimen

As a part of my diet, I regularly eat the following foods:

- Meat, fish
- Olive oil, palm oil
- Butter
- Vegetables, berries, fruit, oats, dark chocolate, coconut milk
- Coffee, tea, wine, beer

I limit or avoid eating the following foods:

- Grain products like pasta, bread, and rice
- Fruit juices, candy
- Vegetable oils high in PUFAs

In general, my diet is high in fat and lowish in carbohydrates. I consume saturated fat and monounsaturated fat liberally but limit polyunsaturated fats.

My supplement regime consists of the following:

- Vitamin D3: 2,500-5,000 IU daily
- Vitamin K2: 90 mcg of MK-7 and 5 mg of MK-4 every third day
- Varying amounts of green tea daily
- Flax lignans: 1-2 tablespoons of ground flax seeds daily

My physical health regime consists of martial arts, running (in the summer), and strength training (in the winter). For mental health, I do things that train the creative and logical sides of the brain.

For more information on anti-aging methods and living longer, see these posts:

Anti-Aging in the Media: New York Times on Caloric Restriction and Resveratrol
How to Live Forever: My 5 Steps to Immortality
L-Carnitine, Acetyl-L-Carnitine and Cognitive Function in Humans
Caloric Restriction Improves Memory in the Elderly