Cell survival, suicide and how to kill them

Unfortunately I did not get this blog finished by my goal (I was hoping to post it yesterday, and it still isn’t finished). So there are a bunch of $*$* flags throughout this post.

But I would like a little feedback on it, so I have posted it as is. Here are the additional topics I hope to cover:

[$*$* This article needs a lot of work. Expand who figured out senescent cells; who first experimented with them; how the experiment was done; when senolytic drugs were first found; how the experiments went; the growing number of people using senolytics; how it is being commercialized; etc.]In humans, any population of older cells will develop senescent cells. These senescent cells should commit suicide (apoptosis) or be killed by the immune system, but in older people increasing numbers of these senescent cells survive.

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These senescent cells do not do their proper function for the tissue they are in. This would not be so bad if they didn’t also emit a large array of damaging proteins that cause inflammation, cancer, and otherwise damage the local cellular environment.

Eliminating senescent cells was first done in mice by the University of Minneapolis in 2012[$*$*verify]. They genetically modified the mice so their senescent cells could be stimulated to apoptosis (kill themselves). This experiment was a great success, extending the lifespan of the mice by 20%.

Since then additional studies have found drugs that can cause senescent cell apoptosis. The first 2 to be researched were diastab and quercitin, a drug combination which clears many senescent cells from mice. More recently fisetin has been found to do the same thing. Now there is a company which is trying to create a drug that works better (none of these can eliminate all the senescent cells from a mouse). Some of these drugs, called senolytics, are available as a supplement over the counter and some are very expensive prescription drugs. Fisetin is a senolytic drug found in strawberries and if you ate enough strawberries you should be able to obtain the same effect as taking the drug, though it would take longer.

A pound of strawberries has about 75 mg of fisetin. It is estimated that 500 mg of fisetin is needed per day for 5 days to treat a 135 pound person. To get this amount of fistetin from strawberries you would need to eat nearly 7 pounds of strawberries a day. That is not really feasible, but you might be able to eat somewhat less for a longer period of time.

While there are a number of self-experimenters around who are taking senolytic drugs regularly, this is not considered wise nor a means to extend lifespan. They should consider what they are trying to do (kill the senescent cells) and what happens if you take drugs all the time (given time, senescent cells may ‘learn’ to evade the drugs). It is best if you took senolytics like they treat mice: you give a course of drugs to eliminate the senescent cells and then you wait for (years?) for the population of senescent cells to build up again before taking another round of drugs. Unfortunately there is not any way (yet) of determining your senescent cell load (number), but I hope that technology is coming soon.

Unfortunately not all senescent cells die with our current drugs. Some remain, so multiple different drugs may be needed to eliminate more than a small fraction of the senescent cells. For example diastab & quercitin manages to eliminate about 40% of the senescent cells in a older mouse.

Fasting has also been rumored to clear senescent cells. I suspect this is one of the reasons many people feel better and have better health when they fast intermittently. But so far there is no way to tell if senescent cells are being killed without doing a biopsy. Hopefully someday soon urine (best) or blood (not so good) work will be able to detect when senescent cells have been killed. If there were some test (like testing urine samples for indicators that senolysis is occurring) then it would greatly simplify doing senolytic experiments. It would also show when the drug has been optimally successful and the treatment should end. Hopefully science will develop this capability soon.

Microlives: a way to measure progress in slowing aging

When you do schooling, science or health you need a yardstick to measure progress with.  School is grades, science is the success of experiments and health is recovery from disease.  Until very recently there has been no way to measure aging progress without waiting for the subject to die.  The problems this caused in the field of aging science has been immense, for aging in worms, flies and mice often have little bearing on human longevity.  We can now extend lifespan in the worm called C. eligans by hundreds of percent, but cannot even try that in humans–yet.  Ever since I have gotten really interested in aging in the early 1980’s the search has been on for biomarkers of aging.  With such a biomarker using death as the endpoint is no longer needed; we can use the biomarker to determining success or failure of an aging treatment.

 So far human aging intervention studies are exceedingly difficult to do for a number or reasons, including compliance by the study’s participants and aging of the scientists doing the study.  Often a really long-term study will be supplanted by new technology making it difficult to proceed when new and better technology exists to fix the problem you are working on.

 Biomarkers are beginning to be used extensively in humans.  PSA (prostate specific antigen) is a good example.  When a man gets prostate cancer the cancer cells produces a lot more PSA which can be detected in the blood allowing us to use it as a biomarker of prostate cancer.  While many people can look at a person and guess within a few years of how old a person is, until recently we could not look at a cell and do the same thing.

Finding the biomarkers of aging has been a key goal of aging science ever since I really started following the field in the 1980’s. Without a way of telling whether your experiment was a true aging intervention (other than the animal living longer) your experiments were restricted to short-lived animals.  This was good for determining the underlying biology of aging, but extending lifespan in a worm that only lives a few weeks, like C. elegans, is a lot different than finding a solution to human aging.

Your genome (DNA) uses something called methylation to help control genes being turned on or off.  The pattern of methylation changes as we age.  This change appears to occur in a very predictable fashion.  At last we have a biomarker that can be used for aging.

The accuracy of this is proving remarkably accurate, allowing us to come within a few years to how much longer you can be expected to live.  While this science is so new it is not yet well researched it is holding out a great deal of promise.  With it we will be able to do an aging intervention and within a few years determine if the intervention has changed the methylation pattern for better or worse.  This will show if the intervention is worth doing, or not. 

So far aging testing using methylation has not yet been approved for use in people.  In the meantime, there are other techniques we can do that tracks how well you might be doing to extend your lifespan.   I like keeping logs and following a lot of data, so the concept of using microlives to track my progress on slowing my aging is feasible. 

The concept of microlives was developed by David Spiegelhalter and Alejandro Leiva.  The general idea is to take a person in their early 20’s who has about half a million hours left to live.  In other words, they would be expected to die in their late 70’s or early 80’s.  Half a million hours is a bit clumsy to think about, so he made it a million-half hour bits of time (science doesn’t really care what bit of time you use, only that it is consistent).  Thus, the term was born: microlives.  His purpose in looking at microlives was to examine what activities is that person likely to, indulge in that would result in increasing or decreasing the number of microlives they were likely to live.  Smoking, for example: 15-24 cigarettes will result in losing 10 microlives (5 hours of your expected lifespan).  Exercising 20 minutes will result in gaining 2 microlives–at least the first 20 minutes you do every day.  The second 20 minutes will only gain you 1 microlife and if you exercise more than an hour a day you may actually start losing microlives!.

All of this data is the result of large studies looking at people’s habits against how long they live.  So if 100 people who exercise 20 minutes a day are compared with 100 people who do not, the average of how much longer they live is 2 microlives or an hour for the first 20 minutes they exercise each day.  So to gain 5 years of life you would need to exercise 20 minutes every day starting when you are 20.  This sounds a little depressing–especially if you are already 50, but if you start looking at all the possible things that can gain you microlives, you will see there are a lot of possibilities.  Enough to add a significant amount of time to your lifespan, even if you are already older.

Some microlives are negative, meaning you won’t live as long if you do these things.  Smoking, eating red meat, obesity, etc.  Many microlives are positive.  20-40 minutes of exercise daily, taking statins, intermittent fasting, eating nuts, having a good social life, eating vegetables, , etc.

I use microlives to help me change my habits toward a healthier lifestyle.  Some have well developed microlives (by that I mean they are well researched so you know what you will gain, like exercise) and some don’t like the habit I am trying to form of not sitting for longer than 10-15 minutes at a time.  I have been working on my microlife habits for a while and in the 2+ years since I began tracking them, I have added more than 200 days to my expected lifespan.  The biggest gains I have made have been from intermittent fasting, where I gain 24 microlives for fasting half a day and 48 microlives for fasting a full day (note: because there is no data on life extension for humans through intermittent fasting, 48 microlives for fasting a day is really just an estimate, derived from the life extension you get in mice when they do intermittent fasting).  Whether this will really prove to be valid is difficult, at this point, to day. 

I also lose microlives.  My greatest loss is my high blood pressure, which I have been struggling with for years.  Because I have seen a lot of negative data about drugs, I am pretty negative about taking drugs so I have been trying to control my blood pressure without them, but my success has been limited.  I am going to make a serious effort at controlling my blood pressure during this 15-week cruise around the world that I am on; if I fail, I will end up on drugs since I think my high blood pressure will be more damaging that the drugs I would take to lower it.  So, over this northern summer (2019 summer in Alaska–since I am currently off the coast of Australia southern winter might be more appropriate to say!) I will try to improve my health sufficiently so drugs will not be necessary.  For a few of the things I will be trying see my previous blog about biohacking.

Some microlives I consider as a loss just because I had the opportunity to gain them, but did not.  Like eating vegetables.  My family is not good at eating enough vegetables, and if I eat 5 servings of vegetables, I gain 4 microlives…but I seldom manage to eat that many in any given day.  Once the opportunity has gone by, you can’t get it back–the next day is a new opportunity for me to try again, but in the mean time I have lost out!

There are other biomarkers of aging but they are less well proven (at least in my mind).  I have not yet done a methylation test to see how my physiological age compares to my chronological age.  I hope to do that this fall, time and money permitting.

5/25/19.  Because I am on a ship where it is really expensive to have internet ($30 a day), I am only getting online twice a week.  But I didn’t manage to get this edited properly, so there is some left to do.  Pardon the gaps and omissions; I will get this finished and will upload it the next time I am online.

 

Biohacking adventures, successes & failures.

Biohacking is a term that has come into common use in the last few years. The do-it-yourself biology movement started in the late 1980’s and has been gaining a lot of momentum in the last decade as people discover small change in their lifestyle can have big impacts on their quality of life. As with many new words it can apply to a variety of things, from changing your diet because you develop allergies to biological experiments with sophisticated technology like gene editing. Who knows what the final definition will be?

To me biohacking means the using awareness of your body to adjust your actions to maximize health. You notice certain things you do, such as those that relieve pain or problems your body is developing and applying those solutions to your life as frequently as needed to prevent the problem, or at least reduce the impact of the problem.
My first biohacks were the result of a plane that I crashed January 12, 1978. In the crash I broke my right leg and the talus bone in my right ankle, as well as a dislocated left shoulder and a crushed left elbow. A year after the accident, when I finally started walking without crutches, I began having bad back pains. I noticed my pelvic hair line in the mirror was slanting down to the right and hypothesized that my leg had healed shorter than it was originally. While the doctor said ‘no’ I decided to try adjusting the height of my shoe until my hair line was level. This required a block of wood 1.5 inches thick. I carved it out so it would fit in a shoe and started wearing it. Within a week my back problem was gone and I still use a bock of wood in my shoe today, 40 years later! Someday I may get special shoes, but I have never seen the point when a ten-cent piece of 2×4 would do the job.

Though I was not aware of the concept of biohacking at the time (1980) this was my first biohack. My second was also related to the accident, because I developed degenerative arthritis in the broken talus bone due to the blood supply being cut off for months while the bone healed. About a decade after the accident a friend of mine (who was, at the time, in his 60’s) was complaining that he could not eat very much beef anymore because it increased his arthritis.

So, I tried decreasing the amount of red meat that I consume, and it seemed to help. As is often the case with biohacking results can be fuzzy. Sometimes when I eat red meat (and I still do on occasion) the arthritis in my ankle gets significantly worse. This is especially true when I eat a hamburger from a specific national chain. Whenever I eat one of these ‘bad’ hamburgers my bad ankle is so sore the next day that I can scarcely walk. Unfortunately, this hamburger is my favorite of any national chain! On other occasions I can eat red meat for several days in a row with no impact on my bad ankle. Usually though when I eat red meat there is enough of an increase in arthritic pain that I notice it and regret eating the red meat.

Noticing results is the key to biohacking. Shoulder bother you? Mine did. It started when I was in my 30’s and slowly built up over a few years until my shoulder started really giving me a lot of pain. The more I immobilized it to relieve the pain the worse it got. Finally, I started doing exercises, lifting my arm over my head. This was a move that really hurt–but over the course of a week or so the pain got less, and now (20 years later) I have very little trouble with it–and when I do a few days of lifting my arm over my head will cure the pain. The gym I go to has a bar that you pull down on with weights attached (so you would be doing a pull-up if you had enough weight attached). When I first tried this my shoulder hurt again even at the lowest weight. After a month of using this machine the pain completely went away–even when loaded to the maximum weight I could pull. This has not been a complete cure, for the problem comes back. But only every few years and now that I know what to do about it the first sign of pain and I go to the gym and a few sessions will fix it for a few more years.

Over the years there have been quite a few other biohacks that I have done over the years, though at the time I was unaware I was doing biohacking. I just would develop a problem, figure out what it took to alleviate the symptoms or cure the problem and implement it. While this may sound easy it usually takes a lot of time, thought and tests to come up with a solution. Sometimes I get luck and hit the solution on the first try (my back problem solved the first try) to my blood pressure which I have tried a number of things to control (from the DASH diet to meditation) without any luck—yet.

When I want to biohack something that I am having a problem with I think about all the various things I have learned about that affects the problem, read up and research these ideas and then try the ones that sound likely to work. My blood pressure is a good example as it has been creeping up for the last 20 years, and is now considered hypertensive. After they lowered the recommendations from less than 140 to less than 120 (systolic) and less than 90 to less than 80 (diastolic). Which now means mine is much higher than recommended.

Two and a half years ago, a doctor recommended I take statins. After thinking about it for a year or so (I hate taking medicine) I started taking them. After a few months I noticed my diastolic BP had decreased nicely. Unfortunately, my systolic continued to rise. Now it is approaching the old hypertensive definition, so I really need to do something about it. This summer I shall try a number of approaches to reducing my blood pressure. If I fail in the fall I will go to a doctor and get prescription drugs (which I hate) to lower it for me.

I want to use my blood pressure as an example of biohacking and try to biohack my way to lower blood pressure. In the process I will demonstrate my approach this kind of problem. I have tried several things in the past, increasing exercise, losing weight, eating more vegetables and the DASH diet (Dietary Approaches to Stop Hypertension). All of these helped some, but then the gain returned and crept back up over the acceptable level.

Please keep in mind that what works for me may not work for you or anyone else; biohacking is often “user” specific. If you want to try my ideas on yourself please be very careful. While I don’t try anything dangerous (I always keep in mind the doctor’s mantra, “do no harm”), expanding them certainly can be (for example immersing your whole body in ice water can be fatal). Any time you try biohacking you should keep in mind the problems that might occur. If in doubt consult a specialist! You want to get better, not worse.

I have known for a long time my blood pressure is too high. Over the last decade I have spent quite a bit of time thinking about the possible ways to reduce blood pressure, and tried a variety of them. Weight loss was the most successful. Unfortunately about a year ago I lost control of my weight (again) and have just recently gotten back under control. So I hope as I lose a little weight my blood pressure will go down.

Over this summer I will try a variety of things to reduce my blood pressure in addition to losing weight. Because I have made several attempts to do this in the past there is no guarantee it will work, but being on a cruise ship going around the world with lots of sea days (i.e. days when the ship is traveling and not in port) will give me plenty of time to try a variety of things.

I have a lot of trouble with weight control, it is not something that comes easily to me (keeping my weight less than obese is a considerable effort). Also, the effect is small, and not enough to get my blood pressure as low as I want (less than 120/80). I need something else that will work.

Some years ago, I rode my bicycle from downtown Fairbanks to my home, which is a 9-mile ride. The last half of that has an elevation gain of about 600 feet, so it is also a lot of work. The day was a beautiful warm sunny day and by the time I got home I had been sweating hard for half an hour. I took my blood pressure and found that it was the lowest it had been in a long time (112/75 if I remember right). So, an hour of sweaty exercise is a likely approach. But a lot of work, which I have not managed to find the willpower and time to try hard, sweaty exercise for a week or so and see if the effect is temporary or more lasting. I will try it on this cruise, but I hope I can also find something else. Or, perhaps, if I can get my blood pressure down to where I want it with sweaty exercise the results will be persistent enough that I will only have to do a long, hard exercise session once a month or once a week.

A few times I have noticed my blood pressure drops sharply the morning after eating leafy vegetables like kale or spinach. Sometimes it doesn’t, so the correlation isn’t clear. So, to start I need to do a statistical analysis on eating a variety of foods and seeing what my blood pressure did the next day (I log all the food I eat plus all my blood pressure daily, so this information is available to me). So what nutrient is in the foods that seem to have the greatest impact? Vitamin K. If this proves to be the case, I will try increasing my vitamin K consumption and see if that lowers my blood pressure. If not then then this analysis should show it.

I have noticed that if I hyperventilate (just a bit) just before I take my blood pressure it is significantly (20 points on the diastolic and 8 points on the systolic) lower. So, I wonder if hyperventilating every hour during the day will result in lower blood pressure that will persist overnight or longer? Note: do not use the technique in the doctor’s office: your doctor needs to know what you blood pressure really is because high blood pressure causes all kinds of problems, and can be very successfully treated with medication, which I will do if it is still high this fall.

Just a few days ago (on 5/15/19) I overhead some people talking about how soaking in ice water lowered the blood pressure of a friend of theirs. I spent the last couple of days thinking about this and came up with some interesting observations from my own life. First is earlier this winter (1/19/19 to be exact) I went for a walk up a frozen stream. This stream had a lot of overflow, that had mostly frozen (overflow is water that runs on top of the ice, usually because the stream has frozen to the bottom and so on top is the only place for the water to go–a common occurrence in many Alaskan streams). I was just trying to get a little exercise, but I got more than that when my right foot broke through the ice into 8 inches (20 cm) of water. I was only wearing tennis shoes, so my foot got very wet.

The temperature was about 0 F (-18 C) and it was a 20-minute walk back to the truck so my right foot was pretty cold by the time I got there. I ran the truck with the heater on high, warming and drying my foot out. The point of this story comes over the next few days, when my right foot (but not my left foot) stayed warmer than my left foot, and I was not bothered by that foot being cold at night which is something I have problems with on days when I fast.

I can think of a couple of possible reasons for this result. One is that I grew more brown fat in response to the cold (possible, but not likely in your feet, is my feeling). The other is that my blood vessels expanded to provide better blood flow. If your blood vessels expand, it should lower your blood pressure so with this idea in mind I searched my blood pressure data from 1/16 to 1/23/19 BUT found no significant change.

I had a similar experience that occurred longer ago, in 2007. Our Alaskan winters are harsh and keeping homes warm is either a lot of work or very expensive (a typical 3 bedroom house uses 1,200 to 2,500 gallons of heating oil a year). So in 2005 when the price of heating oil went up a lot my wife and I talked about whether we wanted to continue heating with oil or if we wanted to start burning firewood. We decided we would rather continue having extravagent vacations (as I write these words we are on a 106 day cruise around the world). Besides we figured cutting wood was going to be a lot of good exercise. We go really serious about burning firewood and reduced our heating oil consumption from 1,200 gallons a year down to less than 100, saving enough money to take a long (3-7 week) cruise every few years, and this long one after 5 years.

During the first few years of cutting wood we had to find dry wood and never managed to get ahead. We wound up going out in really cold weather in search of wood. One time it was -30 f (-35 C) and I was cutting wood in my tennis shoes (because of my bad ankle I haven’t found anything that works for me except tennis shoes, which means I wear them summer and winter in spite of the cold). Cutting wood is hot work and in spite of the cold I was very hot except for my feet. I would jump in the truck and warm them up for 10-15 minutes before spending another 10-15 minutes cutting wood. After working for around 2 hours something odd happened: my feet suddenly started staying warm no matter how long I stayed outside. I am pretty sure they were warm because my body “realized” that there was plenty of heat available so there was no reason to have cold feet, just expand the blood vessels (which normally contract when cold) and let the excess heat from my core keep my feet warm. After that I spent a solid hour outside cutting wood and my feet were plenty warm–and the rest of me wasn’t quite so hot!

When I overheard the conversation about lowering blood pressure through cold, I thought of these 2 instances. While I don’t know if it will work, cold water immersion of my hands and feet is worth trying to see if it will reduce my blood pressure. My example from the soaking I got by falling into overflow may not have had enough time or perhaps 1 limb (my right leg) was not enough to have an impact, so I need to try again to really see if it will work.

Last year I was chatting online with a biohacker who pointed out that some people are sensitive to salt, and others are not. I almost never put salt on my foods, yet I eat enough processed foods that my salt intake is pretty high, as my nutrition logs show. I was discussing online with the biohacker, and he mentioned doing a test for salt sensitivity and it sounded pretty simple so I want to see if I am sensitive to salt. If so, I need to reduce my salt consumption to very low levels.

On this world cruise I am on (mid-May to late August 2019), I want to biohack my blood pressure. I will try each of the 5 things mentioned above for one week each, with a 3 day gap between them, tracking my blood pressure. I will log all the data and post it so people can see the results. Because I want a solution that is solid and persists, I may also try the other possible solutions during this cruise, a week at a time for each one. Hopefully I will get dramatic results and will know which solution works best for me so that I do not have to take drugs to cure my blood pressure problem—and perhaps even stop taking statins. More likely the results will be fuzzy and difficult to interpret. We will see!

Because I want to demonstrate how biohacking works in real life, I will be more formal than I usually am with my biohacking efforts. First, I state my goal:

To use this cruise as a time to try different things and see if I can effect a permanent cure for my high blood pressure. By cure I mean an average blood pressure of less than 120/80 that persists for more than a year.

Initially I want to try 5 possible things to reduce my blood pressure. I will link each of these to the ‘experimental design’ with the specifics of what I plan, what I actually wound up doing and logs of what the results of each trial:

  • Exercise to the point I spend 20 minutes sweating hard.
    • Ice water immersion of my hands and feet
    o This may not prove possible if I can’t get a regular supply of ice and a bucket!
    • Investigate certain foods that have a lot of vitamin K to see if it has an impact on my blood pressure
    o If so try to increase my vitamin K consumption
     If the right foods are not available this may not work well
     If I can’t do it with food, I will try vitamin K pills
    • Assuming I can find them!
    • Mild hyperventilation every hour or 3 to see if lower blood pressure persists after a few days of regular very mild hyperventilation
    • Restrict salt intake to less than 1,200 mg and see if there is any impact on blood pressure.

When doing your own biohacking keep in mind it takes time and the ability to notice subtle changes in your body that show you are on the right track. Or the wrong track! If the condition gets worse, stop and seek a different solution. Sometimes, like with my shoulder pain, the issue will go away for weeks, months or even years. Sometimes the problem is partly alleviated but continues to persist, like my bad ankle. Sometimes the problem is slightly alleviated but then gets worse again, like my blood pressure. Then additional solutions need to be sought like I am trying for my blood pressure.
I would really like hearing about solutions you have tried. Even little things that help reduce pain or improve your standard of living would be appreciated. I would like to hear about things you try that fail too, if I can collect enough information, we can perhaps provide a list of possible solutions to many of aging’s small and large issues.

I do not think biohacking will cure aging. But I do think we can biohack our way into a longer, more enjoyable lifespan. Some things are obvious (if difficult): daily exercise will ensure sarcopenia (wasting of muscle) that occurs in all the old will be delayed; stop smoking; getting good nutrition and building a network of friends and family with which you can maintain a good social life.
Other things are not well enough researched, but hold out great promise: senolytics may help slow the onset of many diseases by reducing inflammation and improving cellular micro-environment; calorie restriction can slow aging in general and has been shown to reboot the immune system; rapamycin (very dangerous!) may reset many of your cells biochemical pathways to a younger age. There are many other possibilities for slowing the onset of old age, in a future blog I will outline a few.

Additional reading:
On blood pressure:
Harvard Medical School article about the new blood pressure guidelines

Medical testing, PCS9 inhibitors & aging conference–an email to a friend

Hi JJ,

 Have you ever heard of PCSK9 inhibitors?  The PCSK9 protein binds to the liver receptor that binds LDL cholesterol, so if you inhibit the protein more LDL is absorbed by the liver, reducing the amount in the blood. 

 I understand a defect in this system results in high cholesterol, I wonder if this is the cause of your high cholesterol?  Either way this is an interesting article.  Unfortunately, the drugs that inhibit PCSK9 are really expensive (over $1,000 a treatment, with 1 injection needed per month (Alirocumab, one of the drugs has a half-life of 17-20 days).  But costs on things like this come down over time–especially since there is more than 1 drug that works.  It may be cheaper overseas (if you can even get it?)

 This article is where I came across PCSK9.  My LDL is 76, which is good by western standards but still not quite as low as recommended.  The article indicates that getting LDL really low (like less than 20) can be beneficial; to do that I would have to take one of these drugs.  So my target is less than 70 which I can probably do with some minor diet changes and increasing my exercise a bit.

 I am overseas now, just got done with the Undoing Aging conference in Berlin at the end of March.  Aging science is really taking off; the conference was sold out (last year 350 people attended, this year 500).  Next year they are going to have to go to a bigger venue to accommodate more people.  While it is great that the concept is getting so much attention, but I don’t like the larger crowds.  

 After the conference I went to Sri Lanka and did a bunch of medical tests.  Most everything looks really good; with just a few things I don’t like (even if the doctor wasn’t concerned).  A few of my liver profile things were not very good, but I haven’t had time yet to research it and see if it is just normal cycling or if it is something I should try to get back into the optimum range (if possible).  Science has come so far these days that you can biohack a lot of different things; we will see what can be done about the liver.  Speaking of which I suppose you know Joe has cirrhosis of the liver pretty bad?  That is really terrible.  I did a little poking around to see about the possibilities of biohacking it but have not come up with anything that sounded worth trying.  Yet–still looking.

 Another thing my medical review showed up is high BP when exercising.  What I did was fine for my age (doctors say), but I didn’t like having to stop the stress test because of high BP.  I have been having issues with pre-hypertension for a few years now, and have increased my consumption of vegetables, nearly met the DASH diet nutrition level and increased exercise rate.  I am usually within the DASH recommendations for Calcium (1,200 mg) magnesium (500 mg) potassium (4,500 mg) and fiber (30 mg)…but have not succeeded in getting my sodium levels down to the desired 1,500 mg.  Meeting the DASH guidelines succeeded in stopping the increase, but it remains high so I want to exercise more…and eat more vegetables. 

 The last bad thing my medical checkup showed was mild osteoporosis.  Which I was kind of appalled at; I always considered my bones to be extra heavy!  *sigh*.  Nothing really to be concerned about yet, just need to be sure to get enough calcium and vitamin D…and more exercise, especially weight training (which I don’t do much of).  Seems like exercise is the answer to most things I have that are tipping out of balance, I better be sure to get more!  

 Speaking of vitamin D, I started taking 2000 units a day in December, and my previously low numbers have been corrected.  But it is still in the lower end of the scale (after I get home, I want to look up how much is recommended for healthy aging–I don’t have the information here).  Since too much vitamin D is toxic, I won’t take any additional until next winter (rely on sunshine this summer); then I will probably increase to 3000 IU a day and do a test after a month to make sure it isn’t too high.

 How is everything there?  After Sri Lanka I came to Japan for a few days and am now up in the mountains (about an hour train ride) NW of Tokyo, where the ski season has ended and this 1200 room hotel is nearly empty (less than a dozen cars in the parking lot).  I came here for peace & quiet so I could get the notes from the meeting typed in and properly researched.  I don’t expect to get them into a form that could be published, but I wanted to at least get them into the computer before I forget the details I didn’t get on paper.  I took 55 pages of handwritten notes at the Undoing Aging meeting, and have gotten most of them into the computer.  Hope to finish typing them into the computer before I start heading home tomorrow.

 Hope all is well there.  Do you still plan to come up to Alaska?  Our cruise plans are progressing, Tamer coming up next month will be a real help.  I am always concerned when I leave the rental business shorthanded!

 Cheers,  Ray

PS as with all my letters I write that have an aging slant, I will be putting this on my blog, DefeatingAging.com but stripped of any way to identify who you are 🙂

 

Dementia

Hi,
     mmm, Paula?  is that right?  My left ear is a little weak (I sure hate getting old) so I am not sure I heard you right?  Anyhow it was really nice chatting with you.
     That was sure a nice memorial they put on for Quint & Cindy.  I really miss them both, though we did not intersect too much after Mom passed away (before then my family used to eat in the Pioneer’s Home once a week, and Quint would occasionally join us).  It was a nice touch to do both memorials at once.
     The book that I mentioned was:
  • The End of Alzheimer’s: The First Program to Prevent and Reverse Cognitive Decline, by Dale E. Bredesen.
     I first heard about Dr. Bredesen’s Alzheimer’s disease protocol about 4 years ago.  I would have been a lot more skeptical except I knew of his work previously, when he was the director of the Buck Institute–a premier research institute in California.  So I feel what he has to say is probably reliable.  The book was a very good read, I will paste in my notes I took below so you can make a more informed decision on whether to buy the book.  If you do all the tests he suggest it would cost more than $8,000–but perhaps you could find a doctor who would recommend the tests and then maybe insurance would pay for it.
     After learning that vitamin D3 was one of the things that was a trigger for dementia I started taking 2000 IU a day.  Usually I am very much against taking vitamins (taking a daily multivitamin will actually shorten your lifespan except in very particular cases!)  I would not take vitamin D3 even now, but everyone in Alaska has low vitamin D3–at least all those I know of who have been tested.  Of course testing should be the basis for treatment (the book has a good formula to figure out how much Vitamin D3 you should take–if you know your numbers).  I will be in Sri Lanka (by India) in April and plan to have my vitamin D3 levels tested then so I will know the optimum dose.  Of course in the summer I will take a lot less, and let the sun make Vitamin D3 for me!
     I am going to do a little testing to see how bad my number are.  I think information is always a good thing 🙂  Testing is pretty cheap in Sri Lanka so I am going to test for inflammation indicators (like C-reactive protein, interleukin-6), cholesterol, vitamin E, homocysteine, fasting insulin, thyroid hormones, B vitamins, heavy metals.  Apparently what is considered a medically reasonable range for many of these is not optimum for brain health, so I recommend getting the book and consulting with a doctor about what the book says before determining a course of action to correct any that are not within the optimum range specified in the book.
     There are a lot of things like leaky gut that can’t be tested for in Sri Lanka (at least not that I know of).  But this will give me an idea of what steps I need to take now so I can talk to a doctor about it reasonably, and if I have symptoms that indicate things like leaky gut I can get the testing done here :).
     I log all the foods that I eat to have a complete picture of my nutrition status.  A few  things that I am typically low on nutrition-wise I have been trying to increase my consumption of, especially B vitamins (low B vitamins are another trigger for dementia, according to the book).  For example I was low on Folate, so I am eating more white beans to assure I get enough.  This and vitamins B6, B9 & B12 are key to reducing homocysteine.  High homocysteine is a major problem in the old because a) they don’t eat enough of these vitamins to keep homocysteine in check and b) sometimes older people don’t absorb as much of these vitamins.  So people get a double whammy with the B vitamins (and some other vitamins).  With my diet logging I could see I was not getting nearly enough of them, and have modified my diet to assure I do.  Which mostly works, but it took a while to change my eating habits.
     If you wanted me to track your foods and send your nutritional levels for a week or so I would be happy to do it–if you didn’t mind my putting the data (unidentified as to who, of course) on my blog DefeatingAging.com (which I am just getting started with; I have a long way to go before I get it working the way I want.)
Cheers,
Ray
PS I may put parts of my emails to you on my blog.  Any response you write will not go there unless you give permission.  Of course I won’t put anything in there that would identify anyone but me 🙂

Ray’s notes on The End of Alzheimer’s, by Dale E. Bredesen
Ray’s reading list

Note about identities: I have changed all the names in my blogs…but if anyone wishes me to use their real name I will–and I will also mention that it is their real name.

Recent deaths

Note: My friend Charley used to live in Alaska.  A few years ago he moved to the Dominican Republic where he has a farm in the mountains.  I still occasionally lure him to Alaska with work, like building micro controllers for my used cooking oil burners.  I use these to heat some of my apartment buildings (so much cheaper than heating oil!).   Charley is a great friend and I have known him for nearly 40 years, and I have always appreciated his support for my crazy projects, like the used cooking oil–or working on aging.  This is an email I sent to him earlier today.

Hi Charley,

 

Not sure if you knew Quint or not, but he died earlier this month.  Did you know he was my Godfather?  I can still remember when I was a child and we kept the old motorhome on his property.  We would stay in it when we were in town from the bush.  He is also the one who taught me amateur radio, so my connection with him goes way back.  I doubt you will be in town, but (just in case) his memorial will be in late January.

 

And then my Uncle died a couple days ago.

 

I sure hate death.  So…wasteful.  And distressing!  I know many think death of the old is natural, and death of the young is terrible.  But I think when the issue is with people you don’t know…death of the old is more damaging because you are removing those who are already skilled and many times the loss of those people have a much greater impact to society than when a baby dies.  Think of how much more Einstein could have discovered if he had lived another 60 years!

 

Both Quint and my Uncle got to be really old.  If they don’t cure aging, I hope I can do as well!  I think they managed to achieve such longevity in part because they remained thinner and because they both remained active and socially engaged.  I also think that fall (up to the winter solstice) is a dangerous time for the very old…all the people I know who are really old have died in this time period (Dad at 85, Mom at 94, Quint at 104?, Uncle at 98…the list goes on…).  I suspect this is because people have a much lower production of hormones during shortening daylight, which makes them more susceptible to (everything).   I think low hormones reduces cellular productivity, which (in the very old) is already defective due to clogging with old proteins, mitochondrial disfunction and the issues with maintaining homeostasis with deficits in protein production.  This reduces their resistance to dying, which means any little thing can push them over the edge.  I wonder if this could be prevented by spending the ‘winter’ in the southern hemisphere?

 

With Dad it wasn’t so important when he died because of his dementia.  But it seems a cure for dementia has been developed in the last few years, though they are still evaluating the procedure.  But it sounds very promising.  Which is really good for me because dementia is something I have been worrying about a lot the last decade, since those nasty ‘senior moments’ has started occurring more frequently!  But I have started thinking about the things they do to prevent dementia (or even partially cure it), and have been trying to implement a few of them.  I am also thinking about being tested for a bunch of the key things that get unbalanced (leading to dementia), like your zinc/copper ratio.

 

All this means changing habits, so it is difficult.  But worth it to gain a lot of extra years of useful life!  I have been trying to increase my level of exercise from my pretty low level to the amount recommended in a book I read recently which is 45 minutes a day, 6 days a week.  The book is called Younger Next Year by Chris Crowley & Henry S. Lodge, M.D.  from which I got 4 pages of notes.  In the book they say regular exercise is (nearly) a cure for aging.  At least it can keep you younger for a lot longer!  It was a good read, so if you get a chance you might pick it up.

 

When I exercise I usually burn around 7-8 kilo-calories (kcal) a minute the whole time I am in the gym.  This includes the total time in the gym, so the average while actually exercising is closer to 10 calories per minute.  I log all my data, so I can figure this stuff out.  It is mostly the number of days that I spend in the gym that is an issue; between the middle of October and the middle of November I was only made it to the gym only 10 days.  The average amount of time I spent in the gym was 46 minutes (so I am doing fine there according to Younger Next Year).  In addition I burn an average of 250 kcal/day walking (I have a pedometer on my phone which logs the majority of my walking).  Here is the total data for those days:
Date Min. exercise time Pedometer calories Kcal in gym Total Cal burn Ave kcal per min. gym
10/22/18 45 305 320 625 7.1
10/23/18 45 152 360 512 8.0
10/24/18 50 387 375 762 7.5
10/30/18 40 324 220 544 5.5
11/01/18 30 274 300 574 10.0
11/05/18 45 198 305 503 6.8
11/10/18 25 235 230 465 9.2
11/11/18 75 233 512 745 6.8
11/12/18 55 197 345 542 6.3
11/13/18 50 216 422 638 8.4
Average 46.0 252.1 338.9 591.0 7.6
So my real issue is getting enough days of exercise, not the duration of each session.  How is your exercise?  I would think you would get quite a bit hiking up and down that mountainous farm!!

 

Your blog looks like it is coming along.  That was really interesting about all your controllers and your internet of things.  Managing your solar power and your water power must make for a lot of time spent programming.  The veggie oil burners you programmed have been doing much better this winter than last, though we had an issue at the 13p a week ago caused by not heating the lines from the external pump.  They got clogged.  Took us awhile to figure out what was wrong with it.  But no issues with the controllers you built to run them, so that is great 🙂  Baranof has been running so well that we haven’t burned the 50 gallons of heating oil we put in there a month ago!  Normally this time of year that place would have burned probably 600 gallons of heating oil.  The 13p is the one that is really going through a lot of oil though; we have been delivering 250 gallons a week of used cooking oil every week.  So much that we are worried about the supply!  We are going to have to increase the amount we gather if we want to keep this up.

 

I am going to put this on my blog too, as I am now trying to keep everything I write about aging there.  Hope you don’t mind?  If so let me know and I will remove it!  Should I add a link to your blog?   Of course as I try to improve my blog I will probably rewrite this a bit, as this is just off the top of my head.
We finally got the 10p boiler install done and fired last week.  Just in time too, because the weather has turned cold.  We have not finalized the boiler in 12b yet, but we need to do that really soon because the one in 12a will not keep up when it is below 0 F.  So the next air quality alert (which is more likely with the cold weather) could really pinch (the last one a week ago was not a problem; we shut down the old boiler and started the ‘new’ one in 12a and everything ran fine).  I am just concerned about the high cost of heating oil!  I anticipate burning 50+ gallons a day, which will put a big crimp in my budget whenever we have to run those.

 

Thinking of you in the tropical weather, here it is -15 F this morning.
Ray

In the beginning…

I am in my 60s and have been using aging research to slow my aging. This blog is about the science behind what I and others are doing to live a healthier lifestyle and hopefully live until science defeats aging.

I am already doing a number of things to (hopefully) slow my aging. I am in my 60’s and over the last decade I have had a few age-related health problems. I have successfully fought off these problems, such as my rheumatoid arthritis; a herniated disk in my neck, cured without surgery; my occasional brain fog is gone; a tremor in my hand is mostly gone; vision problems where I mostly reversed growing farsightedness from my eye lenses getting stiffer and failing to focus on things I read. As I get older, I expect that conquering these issues will become increasingly difficult and the biohacking techniques I have been using will start to fail me. So far my health remains excellent, and with the many treatments coming for slowing the onset of aging diseases I am hoping to extend my health into late old age–and perhaps until aging can be reversed.

Continue reading “In the beginning…”