Longevity

Tidbits of info here:

https://www.youtube.com/watch?v=nN2INcItnRY - HRT, 5 euro p/d? test

https://www.youtube.com/watch?v=S6ARUQ5LoUo Aubrey de Grey, PhD: "The Science of Curing Aging" | Talks at Google EA movement, Bay Area, best way to spend money on humanitarian causes What can you do (impact) and what is uncertainty? (high? for ageing research), so therefore less focus in ageing. - is the problem even solvable? (0x zero is zero) People in the area werent thinking like an engineer, going about it systematically 100 years ago, 1/3 of babies in high income contries died, now there almost no deaths Is ageign the same? solvable problems? But what is ageing? We want good parts (accumulate knowledge) not the bad parts (bad health) Ageing is not emergent phenominon (not like consciousness), it's the same for a car, tree, person, etc - throughout operation there will be damage, accumulate - thing can tolerate damage, backup systems, etc (car, human) -- treshold reached and exceeded, that is all that aging is - there is no mystery of ageing, nothing magical happening - metabolism, you're living, patholigism, you're dead

http://www.sciencemag.org/careers/2003/02/wake-call - uit 2003 XD - This knowledge fed de Grey's natural curiosity about aging. His interest, he says, stemmed from the same self-preserving instincts that most people have: "I'm seriously not in favor of aging; I would really like to do something about it," he says wryly. He became puzzled as to why more biologists weren't studying what he views as "the major unsolved problem" in their arena. - And because no successful attempt to combat aging can ignore that most wily disease of old age--cancer--de Grey has an even more radical idea for outfoxing it. Malignant cells can't proliferate without a way to replenish their telomeres, so he suggests deleting the genes that encode telomerase and other enzymes that perform this task from all dividing cells in the body. - "Most of my ideas ... are pretty damned obvious. But I was the only person in a position to have the ideas, because other people just haven't read the right combination of literature." - He considers aging "a barbaric, uncivilized phenomenon that shouldn't really be tolerated in polite society."

https://www.leafscience.org/lose-weight-feel-great/ FOOD Eat food, not too much, mostly plants (Michael Pollan) University of Southern California professor Valter Longo - Eat mostly plant-based foods, with occasional low-mercury fish or other seafood (2-3 times a week) and lots of nuts and olive oil - Generally eat modest amounts of protein, whether it’s plant-based or animal-based - Very limited or no dairy; goat’s milk and cheese are okay - Minimize saturated fats and sugar - Eat foods from your ancestral homelands as long as they are otherwise healthy - Eat 2-3 meals a day, ideally two solid meals and one snack, in a 10-12 hour window, and don’t eat 3-4 hours before bedtime -- Actionable: Eat between 12 and 20, with small meal before CrossFit - Take multivitamins every three days - A few times a year, if you are under age 65-70 and otherwise healthy, do a five-day water fast or a “fasting-mimicking diet,” which includes food but mimics the benefits of actual fasting. Longo advises strongly against the various “keto” diets that include high animal protein, high fat, and low carbs. While these diets will help you lose weight in the short term through increased ketogenesis, they are likely to lead to potentially serious health problems down the road.

http://www.longlonglife.org/en/longevity/aging/aubrey-de-grey/transhumanism-aubrey-de-greys-causes-of-aging-with-sens-foundation/ Aubrey de Grey is one of the leading figures in anti-aging research. He is the co-founder of SENS, a California-based research institute dedicated to anti-aging research with a strong focus on regenerative medicine - We have a cellular metabolism, which corresponds to everything allowing us to live from one day to the next and makes our cells function. This metabolism accumulates, over time, damage, intrinsically related to its operation which is not without errors. This damage, when it accumulates, causes pathologies and causes us to age. - focuses on an engineering approach, the aim of which is not prevention but pure and simple treatment of aging - 7 causes of aging: Intracellular waste Intercellular waste Nucleus mutations Mitochondrial mutations Stem cells loss Increase in senescent cells Increase of intercellular protein links - cellular waste: our cells will also produce waste products that need to be disposed of. Extracellular waste, exra proteins outside neurons (Alzheimer). -- intracellular waste: garbage truck machinery jams (macular degeneration? or atherosclerosis) - genetic mutations: nucreal mutations, changes in DNA (cancer, diabetes) - hereditary but also emergent (errors in copying) -- mitochondrial mutations: are energy cells (ATP, NAD), has own DNA (codes for 13 proteins), same errors - Managing cell stock: less stem cells, more senescent cells (zombies) - Protein interconnections: more connections over time, less elesticity (arteriosclerosis) - robust human rejuvenation: breakthrough that will lead to extra 30-50 years of healthy living - longevity escape velocity: exponential increases

http://www.newyorker.com/magazine/2017/04/03/silicon-valleys-quest-to-live-forever If you can crack the code, you can hack the code! “thermodynamically, there should be no reason we can’t defer entropy indefinitely. We can end ageing forever. Joon Yun Verily - enjoy a few more “quality-adjusted life years.”

CGP grey video

Lately I've become interested in aging. Why do we age? What can we do about it? And is death inevitable? I don't have many answers yet. The research is ongoing and scientists are discovering new things every week. Below is a video from TED. In it Tony Wyss-Coray discusses how young blood may reverse aging. The studies show that it works in mice. The first trials with humans have started at Stanford. If you have 13 minutes to spare, I would recommend watching the video. Tomorrow I will outline some more of my thoughts about aging. https://www.youtube.com/watch?v=CsECS5qsGLs https://www.youtube.com/watch?v=CsECS5qsGLs&index=81&list=WL

https://www.youtube.com/watch?v=EvaC67CeBDA

https://www.ted.com/talks/aubrey_de_grey_says_we_can_avoid_aging

https://www.technologyreview.com/s/609576/undoing-aging-with-molecular-and-cellular-damage-repair/?set=535821 - SENS Research Foundation is spearheading the fourth age of anti-aging research: the repair of age-related damage, that is, rejuvenation biotechnology. - The Strategies for Engineered Negligible Senescence (SENS) approach was first proposed in 2002. “Senescence,” here, refers to the actuarial phenomenon—the trend that individuals within a population suffer from an increasing morbidity and mortality rate in (typically exponential) relation to their chronological age. “Negligible” is used in a statistical sense: we consider a level of senescence negligible if no age-related contribution to mortality is statistically demonstrable within a population, given the “background noise” of age-independent mortality (such as unfortunate encounters with motor vehicles). Finally, by “Engineered,” we indicate that this state is achieved by the deliberate application of biomedical therapies, and is not the normal situation. The goal of SENSE is thus unambiguously defined; we seek methods to convert a population experiencing a non-negligible level of senescence into one experiencing a negligible level. - Analogy: car, vintage, repairs, still good - indefinite period - Aging can be characterized as a three-stage process. In the first stage, metabolic processes essential to life produce toxins. Secondly, a small amount of the damage caused by these toxins cannot be removed by the body’s endogenous repair systems, and consequently accumulates over time. In the third stage, the accumulation of damage drives age-related pathology. - Consequently, its dynamic metabolic processes will revert to their own norms, and the risk of mortality will be no higher than in any other equivalently “youthful” individual—whether they have actually lived for twenty years or 120. Furthermore—so long as our inventory of damage classes is sufficiently comprehensive—we can repeat this effort on a regular basis, and thus remain indefinitely below the threshold of pathology. - Crucially, we can do this without a comprehensive understanding of the complex metabolic processes giving rise to damage, nor of those leading from damage to pathology. We need only an inventory of the types of damage which exist, which can be obtained directly by comparison of older and younger individuals. - fortunately, it seems that all aging-related damage known to accumulate in the human body can be classified into just seven clearly defined categories: cell loss, cell death-resistance, cell over-proliferation, intracellular and extracellular “junk”, tissue stiffening and mitochondrial defects. -

Aging and Caloric Restriction Caloric restriction in lab mice has shown to increase lifespan by 20-30 percent. This happened when they fed the mice 30-40 percent less than they would normally eat. The mice also didn't develop cancer, diabetes, heart disease, or obesity. They also have low blood sugar levels, low insulin levels, good insulin sensitivity, low blood pressure, and better general health. But not psychologically. Nope, eating less than your body needs/wants has a negative impact on your mood. The lab mice showed signs of depression and irritability. In a human study, the test subjects also didn't have fun. So what to do, you want the benefits but not the downside. Intermittent Fasting (IF), reducing calories for only a small portion of the time, has the benefits of the fasting group without the downsides. Notable doctors have tried it themselves and report the benefits. How to apply IF Eat less on some days. Well, that's the very short explanation. The benefits of IF should show up at a 24-hour mark, so this means that you don't have to go without food for a whole day (because then you wouldn't eat for 36 hours when you account for sleep). You can eat breakfast and lunch the one day, and eat dinner the next night. Does IF work in real-life? The great benefit if IF lies in combatting aging (and related diseases). A side-benefit could be weight loss if not all 'lost' calories are accounted for in the day after. But at the same time, it's been shown to lower thermogenesis (your resting metabolic rate), thus negating the loss of calories by making your body more effective. A study with young overweight women showed no benefit of IF over continuous energy restriction. Both methods had a positive effect on the body weight of the women (both about 6kg over 6 months). The insulin sensitivity and other health markers also didn't differ significantly. The psychological effect of IF versus caloric restriction wasn't measured. Another study with an alternating-calorie diet produced the same results. Here they studied if eating high and low-calorie days had any positive effect. The changes were, however, the same as the test subjects who ate less every day. What  they did find was that exercise was beneficial in both groups (versus no exercise). Take-away Reading more and more about the topic (see sources below) makes me realize that there isn't a definitive answer to give here. Fasting can have a positive effect on our furry friends, but on humans, the effect may be smaller. And IF is one of those things that might be difficult to do in a social setting. I'm doing the semi-fasting as per the 'food and aging' article. After that, I will cycle my calories, mostly just to keep things interesting and to know for sure that my body has enough calories on the days that I will sport intensively. But every day I will be eating about 2000 kcal (or way more) so caloric cycling is the only thing that might apply.

Periodical Fasting What do you have to do? Reduce your calories by up to two-thirds, over five consecutive days, once every three months. What happens? In the short-term you lose a bit of weight, but that’s not what it’s about. In the long-term it could start a regenerative process that will lead to improved health and a longer life. It could lower the chance of cancer and strengthen the immune system. Even cognitive ability could improve and the chance of getting diabetes could be nulled. Why does this happen? Before we can understand why this happens, we first need to know a little biology. Our bodies make growth hormones (GH) and normally these are secreted by the pituitary gland and are processed by the liver. Here they are normally turned into insulin-like growth factor-1 (IGF-1). IGF-1 stimulates cell growth and division. When a person is unable to process GH and in effect won’t make IGF-1, he or she will have stunted growth (e.g. dwarfism). This person will also have a less likely chance of developing cancer (less cell division) and almost no risk of developing diabetes. And that is why you want to fast, this helps repress the production of IGF-1, and the effects are longer lasting than only during the (semi)fast. So, what do I have to do exactly? Eat 1100 calories on day 1, eat 725 calories on day 2-5 Don’t binge beforehand, this will only make it more difficult to adhere to the plan The first day is the most difficult, soldier on Eat a high-fat, low-protein diet on those days Don’t forget to supplement vitamins Drink enough water Be prepared for headaches (possible when body starts to use fat instead of glycogen for energy) 95% of people stuck it out, don’t be the 5% Side-effects You lose between 2-4kg of weight during the (semi)fasting period (not all fat of course!) You might be less prone to snack afterwards (breaking bad habits) You may experience both mental clarity and drowsiness [/et_pb_text][et_pb_toggle admin_label=”Toggle” title=”SOURCES” open=”off” use_border_color=”off” border_color=”#ffffff” border_style=”solid”] An experimental eating regime may slow aging and stave off disease–if you can stand it

https://a16z.com/2018/12/23/extending-human-lifespan-longevity-bioage/ Where are we now, 3 examples of things that are in clinical trails. Blood, metformin, ...

https://milan.cvitkovic.net/writing/longevity/ Good review, read!

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