Blood of world’s oldest woman hints at limits of life
newscientist.com
newscientist.com
It’s estimated that we’re born with around 20,000 blood stem cells, and at any one time, around 1000 are simultaneously active to replenish blood.
I was surprised the number was so low. Interesting to think this relatively small number of little factories has to sustain us throughout life.
Next question: Does the number of stem cells scale with body mass? Because if that's the case then I give you the Naked Mole Rat (aka the penis with teeth https://en.wikipedia.org/wiki/Naked_mole-rat ). The Naked Mole Rat is _THE_ model organism for longevity, completely defying extrapolation of ageing models. The average Naked Mole Rat weighs about 30g, the average human weighs about 75kg. So a Naked Mole Rat hat about 1/2000th the body mass of a human. Assuming a mass proportional stem cell count that would make about 1000 stem cells in total and 0.5 stem cells replenishing blood cells at any given moment.
Where does these 20000 and 1000 figures come from in the first place? Given my personal experience in TA-ing students of medicine and biology I don't have a lot of confidence in their calculation abilities. These students manage to get their figures wrong by several orders of magnitude on a regular base. So I'd not be surprised if these figures are grossly underestimated.
Dopamine neurons in the brain are essential for normal functioning. Parkinson's develops when dopamine neurons die off with age or due to other injury (toxins, trauma, etc.). It takes only a 15% loss of these irreplaceable cells for the condition to begin to show up.
In contrast to the cortex of the brain with its 100's of millions of neurons, we are born with only 250K dopamine cells which are never regenerated.
That's a narrow margin to rely on, we skate on very thin ice throughout our lives. Nature is the staunchest conservative and doesn't throw away the things that work. Our bodies still retain the archaic mechanisms of the earliest multicellular organisms in our brains and bodies.
Looks like blood forming tissues are similarly following Nature's way.
In engineering an idea that has been found to work in one place gets adapted in another. Also you often build reliability through adding layers of redundancy.
Evolution has no straightforward way for good ideas to be identified and reapplied to another system. It has to evolve again. Also if you have two fully redundant systems, there is nothing to stop deleterious mutations from disrupting one of them. The end result is that one of the redundant systems will become unreliable, and then the other one gets maintained by selection pressure. (This is also why creatures that live in a cave eventually become blind, and parasites lose their ability to use now unnecessary body parts. There is no engineering reason why this would happen, but is a natural result of selection pressures being eliminated.)
Hence the "features" or "redundancy" which would otherwise consume resources and not significantly affect procreation chances (like your cave example) eventually get selected against and disappear.
"Good Engineering" on the other hand usually devotes additional resources to redundancy, fault-tolerances, which do not necessarily offer a competitive advantage in procreation.
It's not that simple. If producing the maximum amount of offspring were the goal, populations of a species would quickly collapse. It's also a poor principle to explain social behavior and organisms living in hives or strictly hierarchically procreating groups.
A much better model principle would be, that evolution optimizes for maximum probability of the _offspring_ to successfully procreate. By adding this layer of indirection a lot more of what we can observe in biology can be explained with less presumptions (Occam's Razor).
My post was just layman speculation, as I'm not a biologist/ecologist.
Because every individual started with one single cell, from a father and mother cells that also underwent cell division
Hence at some point in time these telomeres get rebuilt/replenished.
https://en.wikipedia.org/wiki/Telomere#Structure.2C_function...
Of course high paternal age also has other risks, but there's a sweet spot sometime between 25 and 30.
Still, mice and humans have different telomere dynamics, and so it is wise - I think - to be wary of the cancer risk question. More testing of telomerase overexpression needs to be done in other mammals with more human-like telomere dynamics.
So maybe the genes for reduction of telomerase have evolved because by (older individuals) dying the survival of newer individuals (who are offspring of those) is facilitated due to less competition for resources?
1) Telomeres shorten with each cell division in ordinary somatic cells. When they get too short, cells self-destruct or stop dividing. So average telomere length in tissue is a function of cell division rates.
2) Stem cells support their associated tissue type by providing new cells with long telomeres. Thus average telomere length is also a function of cell replacement rates.
3) Average telomere length is at present usually measured in white blood cells. The rates of division and replacement here are tied in to many factors, including general health, autoimmunity, infection, state of the thymus, and so on and so forth. It would probably be better to use another tissue, such as skin, but that isn't the way things worked out in practice.
So telomere length is far removed from first causes in aging - it is largely a marker, largely of stem cell function in most tissues, but in immune cells with their varying rates of division according to circumstances, also a marker of all sorts of other unrelated or partly related things.
If telomere length is globally extended, you have cells that can divide more often without the need for stem cell support, and you also have more energetic stem cells. But those cells dividing more often are more damaged on average. This may or may not be important enough to do bad things such as raise cancer risk significantly in our species: more data needed.
[1] http://www.bloodbook.com/storage.html [2] https://www.newscientist.com/article/mg22329831-400-young-bl...
There is some evidence that frequent blood donors live longer than occasional donors. Being healthy is a selection criteria for blood donation, so it can be hard to study the impact.
http://www.bloodjournal.org/content/bloodjournal/98/10/2900....
From an engineering perspective what are the MTBFs for the various human components; are a dearth of White blood cells a prime reason for aging and death?
Great progress has been made in genetics surely one could read the DNA of a few thousand cells and have an extremely strong confidence of what the unmutated DNA for a person once was.
And from this you could make new white blood cells et voila.
This all seems rather Blade Runnery. Mind you there would be societal problems with people who can live much older: slowing of cultural evolution, career blocking, and monopolising property; we've got that now but it would get worse.
I'm worried about the Brexiters kicking out the metric system;that and fascist tyranny.
https://en.wikipedia.org/wiki/Reliability_theory_of_aging_an...
http://www.ncbi.nlm.nih.gov/pubmed/20469937
Immune system aging is an important component of age-related frailty, and probably also accounts for the rising number of senescent cells and higher cancer risk. It isn't as simple as a dearth of cells, however. It is more of a complex configuration/whole-system failure in which rate of cell replacement is just one variable contributing to the bad state endpoint. See for example:
https://www.fightaging.org/archives/2006/12/when-and-how-doe...
https://longevityandhealthspan.biomedcentral.com/articles/10...
So there are a finite number of T cells, and nearly all of them are used up fighting Cytomegalovirus?
Having a blood transfusion from someone younger than you will increase longevity.
https://www.theguardian.com/science/2014/may/04/young-blood-...
So it pays to be a vampire!
http://worldnewsdailyreport.com/david-rockefellers-sixth-hea...
Maybe this would be better? http://www.academia.edu/12568086/DAVID_ROCKEFELLER_S_SIXTH_H...
Hashes are useless if you have downloaded compromised software/distro/what have you from spook servers. Just hash the compromised software, the unthinking will see the hashes match but not realise what has been downloaded is already compromised.
It pays to plan decades ahead.
> Our goal is to help build the industry that will cure the diseases of aging.
I'm not saying you're wrong...I just think there's some confusion online as to what they really are trying to do. They don't research aging in general, which would imply they are a University Body whose sole function is research for the purpose of research...they are specifically attempting to create a kind of science, which may or may not be valid, by funding certain types of research done by recognized research institutions, with the hope that evidence will support what they believe to be true...sort of like how the Koch brothers fund all sorts of research hoping to poke all sorts of holes and nuances into the accepted version of how climate change is understood. They may very well come up with something interesting, informed, and comprehensive...but that does not mean that they are being realistic. In research you don't get to choose whether your hypothesis is realistic or not...you just sort of go out into the woods and start picking things up and seeing whether what you think the laws of nature are...really are true...but you could be completely wrong and you might find nothing. You don't get to choose whether you catch a fish...you may come back to shore with zero fish after fishing for 50 years...or 100 years...or an infinite number of years.
I don't think you can say it's wrong in wholesale at this point, given where things stand. The mainstream position in the aging research community is that aging is caused by an accumulation of damage.
Senescent cell clearance has been on the SENS agenda since day one, with plenty of evidence to back it as a cause of aging from the past decades of research. Life extension has been demonstrated in mice through senescent cell clearance. There are two funded startups moving senescent cell clearance therapies to the clinic.
You'll also find it hard to argue against the proposition that amyloid causes specific age-related conditions. E.g. amyloid beta in Alzheimer's disease, transthyretin amyloid in heart disease. These are very mainstream concerns.
Similarly, there are few objections to the idea that declining stem cell function is a cause of aging, and plenty of evidence to show that restoring stem cell activity is beneficial.
And so on.
In food that's been fortified, it will probably have D2, while food that has natural vitamin D (like fatty fish) will probably have D3.
Although the two forms are metabolized through different mechanisms, the difference is negligible for most people. However, for some people (depending on genetics, diet, or lifestyle), supplemental Vitamin D2 will not be an adequate replacement for Vitamin D3.
I prefer the sun or lying under my UVB lizard flo tubes for an hour a day.
If you do want to get high levels of d3 in your body, make sure you also increase at least your zinc, magnesium, and eating your greens, brussel sprouts, parsely or iodine rich sea food like seaweed will all help, but you really need to be in tune with your body and its cravings to know what your body wants. http://nutritiondata.self.com/foods-000104000000000000000-w....
Some foods and drink will blunt or dull your food cravings like sugar.
Vit D2 is not as beneficial as D3 to humans, but you get D2 from some plants like mushrooms exposed to UV light.
You have to bear in mind humans like all life on this planet has evolved under the sun over millions of years. Life evolves to cope with the environment it lives in, ie survival of the fittest.
BTW if you want to be naturally exposed to anthrax, get friendly with some sheep.
Thing is though, its not just Vit D people should be focused on, in general its a healthy balanced diet with plenty of sunshine and exercise which is best.
This chap, http://www.creditonparishchurch.org.uk/history/sir-john-de-s... is an example of how long life can be gained even when the life expectancy all those years ago was relatively low due to the statistics and infant mortality which dragged down the life expectancy see back in medieval times.
Can you point me at a reference for this info?
http://news.bbc.co.uk/1/hi/health/7083323.stm
The sleep hormone melatonin increases the release of mesenchymal stem cells, and is also more effective as an antioxidant than say Vitamin C amongst other things. http://www.ncbi.nlm.nih.gov/pubmed/24650016 http://www.benbest.com/nutrceut/melatonin.html#aging
A book called A Million of Facts by Sir Richard Philips published around 1839 states on page 148 "Riley asserts that Arabs, in the desert liver for 200 years."
Lots of UVB in the desert!
The Welcome Trust in Aug 2010 stated there are 2,776 binding sites for the Vitamin D Receptor in the Human Genome, most of which are concentrated around the immune system genes. https://wellcome.ac.uk/press-release/vitamin-d-found-influen...
Yes genes can change in the body.
Water Fasting is also the other major factor in long life as your lysosomal enzymes come into play. https://en.wikipedia.org/wiki/Lysosome
Some people have stated that military medical experiments on fasting carried out around the time of WW2 to learn how best to deal with starved prisoners of war, have shown moles on the skin have shriveled up and disappeared, and grey hair has also returned to its natural colour amongst other rejuvenating effects. A variety of studies have shown improvements in the body, ranging from increased spatial intelligence (ghrelin the hunger hormone) to better survival rates when undergoing various cancer treatment protocols. Loads can be found using google scholar, but heres just one recent example.
http://www.telegraph.co.uk/science/2016/03/12/fasting-for-th...
On the point of lysosomal enzymes, if fasting, once the body has digested the food in the digestive tract usually 3 days, around day 3-5 it goes into a ketogenic state, in fact a ketogenic diet is sometimes used in cancer treatments to increase the effectiveness of the protocol, although it certainly helps deal with the toxic side effects of some protocols.
http://stm.sciencemag.org/node/186102.full
Interestingly some lysosomal enzymes are only activated after 10 days of fasting, today how many people fast for this length of time?
I cant help but notice some parallels with Lent, in the distant past before modern medicine, Lent was about fasting, today its only about giving up something for a period of time. I also cant help but notice that when Jesus was crucified, he would have been effectively fasting on the cross whilst also being exposed to copious amounts of sunshine leading to an increase in Vit D, although the nitric oxide is the most notable short term effect as it takes Vit D about 14 days to become activated in the body afters its been processed by the kidney's and liver where all your fat soluble vitamins are stored.
After Jesus was taken down from the cross, and banged up in a dark cave, melatonin would have increased effectively helping him to come back from the dead! Bear in mind modern medicine was around back then so whilst it can only be considered supposition, there are some circumstances which could have certainly brought him back from the dead, if he wasnt really in a deep coma.
Numerous instances of people coming back from the dead even today occur which get classed as miracles and some mammals will fast if they dont feel well.
Before anyone rushes off to try to fast, there are some precautions you should undertake. Namely never get cold, cold is a very effective killer when fasting. You also need to increase your Vit A intake, best source is eating liver, and whilst some might caution against taking too much Vit A, UV will destroy Vit A in the skin, and zinc binds the Vit A in the liver into something called Retinol Binding Proteins, which then moves to other parts of the body, improving things like the mucous membranes in the digestive system, lungs and elsewhere. In a way Vit A will improve the digestive system helping your body to absorb more of what it needs from the food you consume, so is a good place to start. Vit A primarily benefits the innate immune system which is what keeps you alive in your final years, Vit D benefits the adaptive immune system.
I think its also interesting that animals whose habitats are closest to the poles have the highest levels of Vit A in their body, yet those living near the equator have the highest levels of Vit D.
Its also worth pointing out that as more people no longer work the land but are indoors so much, one could argue that todays lifestyles are not always so good for us.
Take this study. https://www.vitamindcouncil.org/blog/washing-away-vitamin-d/
In the old days, its routine to just wash your pits, feet and groin and have a bath once a week. Today everyone showers. Its also worth pointing out that we can absorb ions through the skin, more so in those regions where we sweat the most, but we see examples of this from things like nicotine patches, mag oil (magnesium chloride mixed with water) as well as Epsom salt baths (magnesium sulphate) although the body will excrete sulphate faster than chlorides. Magnesium and zinc are very useful for Vit D, as there is a zinc finger on the Vit D Receptor.
I could go on, I've read hundreds if not a few thousands of studies for over a decade now on this subject, but you have the most important info here. However like everything no one thing is a panacea, so even if you do get enough Vit D, if you dont have enough Mg or Zn as a couple examples, you are not neccesarily getting the full benefits. Coupled with todays more toxic polluted lifestyles millennials will not live as long as those born around the end of the 18th and 19th century which data today is now starting to suggest.
Even Vitamin RDA's which came into existence around the 1950's are set so low as to only help prevent the worst of illness, eg Vit D RDA @ 400ui is generally enough to prevent rickets, Vit C just enough to prevent scurvy, iodine just enough to prevent goitre's as a few off the top of my head.
I'm just a programmer not medically trained but I can read and apply logic and questions to studies I have read whilst I wait for the compiler to complete, but I dont suffer from Milgrams obedience to authority though, so I question everything.
Check out Fasting by the Hygienists for more info on fasting, for a starting place or even find out about the Fasting Olympics which took place around the 1900's, the 1903 one took place in New York, and dont be tempted to overdose on some vitamins, as some chemicals classed as vitamins are toxic if consumer above the RDA levels, Nicotinamide (Vit B3) being one such when compared to the safer form Niacin, although getting your B vits from liver is best as digested slowly.
Worth noting that most man made vitamins in pill form will behave in the same way as medicines/drugs as noted in this article. http://www.smithsonianmag.com/smart-news/we-used-recycle-dru...
So there is some truth in what Dr's used to say when they said "you are what you eat".
A couple of problems with that "theory". Vit D is produced in the skin by conversion of precursors on exposure to UVB radiation in sunlight. However, the amount of vit D in total is bounded by the quantity of substrate and rate limiting as vit D is produced. Therefore sun exposure never produces excessive systemic levels of vit D.
Furthermore, human residents of the biblical era in the holy land would likely have good vit D storage levels by default. Additional sunlight would not materially increase circulating D level.
I did an experiment a few years back working on laptop outside in just shorts during UK summer. I got my levels up to just under 500nmol/L (478nmol/L iirc) verified by the Vit D centre at the NHS Birmingham and Sandwell using their blood spot tests, sending one of their bloodspot tests to them a month. http://www.vitamindtest.org.uk/vitamindbackground.html
200-220nmol/L is considered the safe upper limit, 500nmol/L is considered toxic, I was warned if I went higher I could get sarcoidosis which is granulation of the lungs amongst other things. However the NHS medical person who has a PhD in Vit D that worked there, who I had a lengthy conversation with on this topic didnt know the role iodine plays at killing cells in sarcodosis, only hypothosised in Greece in 2013 and didnt know about the 1937 study of how water washed off pre-vit D from the skin.
Likewise if you get too much 25(O)HD circulating other risks to health include hypercalcemia, ie too much calcium circulating in the blood which can lead to things like stones and other problems.
As Vit D increases the absorption of calcium from the diet/gut, you then need the fat soluble vit K to move the calcium from the blood to the bones as Vit K increases oesteoblasts (bone building), or increase iodine so the thyroid can release more calcitonin (amongst other hormones) which gives you a similar effect to Vit K. Your diet also affects what you produce as well, my diet is generally ketogenic. Your liver produces around 80% of the cholesterol which is needed to become Vit D. In fact a study in the UK done sometime in the 50's showed British gardeners had lower cholesterol levels, so you can lower your cholesterol by getting some sun. Of course if you have damaged your liver through excess alcohol, smoking or drugs then your liver is not working at optimum and thus you need to increase your dietary cholesterol intake whilst also increasing your consumption of B vits to help the liver regenerate as its the only organ that regenerates naturally and this is how they used to treat people with liver cirrhosis in the early 1900's.
As mentioned above with Vit D, theres a few different forms of Vit D and Vit K to name a few, in fact one Japanese study showed Vit K2 MK4 is used to treat post menopausal women for osteoporosis but then reducing vit k is used to thin the blood to prevent heart attacks. Fat soluble vits have a have life in the liver, Vit A has the longest half life, followed by vit D, then E then K with some forms of Vit K only lasting for a few minutes to hours to a few days depending on which form of vit K it is.
Anyway whilst I have seen studies to suggest the Vit D is rate limited by your body, I proved its still possible to get above what medical experts consider the natural limits in the body. You see melanin the skin pigment/tan converts 99.9% of UV radiation into heat, the skin cancer risk comes from burning too much, you want to build the tan little and often to maintain the tan all year round, but melatonin whitens the skin. UVA reactivates melanin, UVB creates new melanin. Copper stored in your liver is oxidised to become melanin. Likewise if you dont have enough Vit A your skin wont produce enough oil which becomes UV radiated and is where you find the pre-vitamin D, likewise showering even in just water every day washes off the pre-vitamin D, so I dont agree with some of things Hollick (arguably the worlds leading expert on Vit D) says, plus there is the cholesterol angle to also help increase Vit D. Your brain is made up of a large amount of cholesterol as well, which is why some studies have shown some statins make people forgetful when on them. If their liver is not producing enough cholesterol, how can your brain keep working properly?
So, yes I can agree with you that there is going to be a rate limit to the amount of Vit D that shows up in blood tests, but depending on the type of Vit D test you do, depends on the levels it shows. You see different manufacturers who make the machines which calculate the levels of Vit D in the blood use different protein markers, so theres now a group underway to standardise the levels across all the different machines and methods used. More info here. https://ods.od.nih.gov/Research/vdsp.aspx
> Additional sunlight would not materially increase circulating D level.
Due to pollution, we get less sunshine today which has also been spotted with things like some frogs not reproducing as much today compared to just a few decades ago such is the rise of atmospheric pollution, global dimming et al, but you need the sunshine to start the process or get yourself some of these to lie under like a lizard. ;-) http://www.uvguide.co.uk/lightingsurveyintro.htm Its also interesting to note that UV levels do vary around the world as noted here. http://www.uvguide.co.uk/uvinnature.htm
If you live in a town or city, vehicle pollution reacts in the sun to create ground level o-zone which blocks uv-b, yet 100% of uv-b is reflected from man made surfaces like concrete so whilst you can get the best exposure to uvb in a town or city due to the manmade materiasl reflecting it so well when compared to plant matter, its restricted by the ozone pollution. In the countryside around 30% of uvb is absorbed by the plants, yet due to little or no pollution, realistically you get more uv-b exposure being in the countryside even though plants take around 30%.
Like I said, I have read alot of studies and having a high signal lesion in the genu of the corpus callosum which I found out when I had a MRI on my brain also helps retain this data.
Studies have also shown high levels of Vit A and D enough the pancreas to start producing islet cells so you can have expensive stem cell therapy if you are diabetic or if you cant afford that get you A and D levels up. All of this info and more can had for free by reading the studies you find when using google scholar.
To quote Thomas Pynchon, if you dont ask the right questions, who needs to worry about the answers? Same applies with google and other search engines, if people have an inquisitive mind.
Interestingly some lysosomal enzymes are only activated after 10 days of fasting, today how many people fast for this length of time?
This is super interesting. What is the source for the 10 days number - is it in the article you linked? Do you know where I can get full text - it is behind a paywall for me.
I was always interested how long does it take to get most benefits out of fasting, but research on anything over 72 hours is very scarce.
Edit: found it here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3608686/
Animal studies again. Nothing wrong with that, I'm convinced that fasting has a range of benefits, but human studies would be just so much more interesting.
Still looking for the source of the 10 day figure for lysosomal enzymes and humans.
So you should make sure not to have any if you get cancer.
Lymph seems to be a passive system ie its not pumped like blood is.
Melatonin is good for a variety of reasons which is probably why its called beauty sleep, its also one of the few substances that can cross the blood brain barrier like caffeine does, and that in turn increases dopamine.