Aubrey Updates on Antiaging Progress and Timing

In his talk at Ending Age-Related Diseases 2019, Estimating the True Complexity of Comprehensive Rejuvenation, SENS founder Aubrey de Grey talks about the intricacies of creating a complete rejuvenation biotechnology framework, including the differing rates of age-related damage and the ramifications of the extensive crosstalk between different types of this damage.

The reason for grouping aging damage into seven categories was to group them based upon the likely mechanism for repair. Immune therapy work against Alzheimer’s amyloid. The same immune therapy should work against amyloid in hearts and the cardiac system. The amyloid problem for the cardiac system is a leading killer of supercentenarians.

There have been new forms of aging damage found over the past twenty or so years since Aubrey de Grey came up with the SENS theory of antiaging. However, the new damage fit into the existing categories identified by Aubrey. This may not always be the case.

Most types of aging damage are multi-step processes. There are intermediate products that are repairable.

If we are able to fix and prevent irreparable damage, we will be enabling the pre-damage repair systems to again get ahead of damage accumulation.

There seems to be more overall antiaging benefit from fixing one category. The removal of senescent cells has made mice broadly younger. This could make radical antiaging more feasible.

Aubrey argues we do need to get a better assessment of how difficult and complex achieving longevity escape velocity is. This will help us prioritize the most promising areas and determine if other approaches should also get emphasis.

53 thoughts on “Aubrey Updates on Antiaging Progress and Timing”

  1. Some of you are trying to compare an genius to the way you behave and think. That’s not fair, one must not judge someone else, without walking in their shoes.

  2. I’ve seen this as dating advice for men as well. If you try to look normal/inoffensive in every dimension, you won’t be a turnoff to everyone but you also won’t excite anyone. But if you go for a “look” (any look, not just weird piercings), you become a scarce resource for whatever group likes the look.

    Maybe this is true for Aubrey de Grey too. Gandalf fangirls could be crawling all over him at conventions.

  3. Congrats to your Aunt…she won. Keto? It is probably possible to also keep down AGEs while on a keto diet…challenging…but not impossible. Lots of low carb veggies, avocado, pistachios, no frying, raw sunflower seeds, steamed seafood.

    Jury’s still out on keto. We don’t know the long term effects. It is not natural…that is clear. Some of this stuff got started because Inuits did not get heart disease even though they eat large amounts of fat. Turns out they had a gene variant that protects them at a cost of about an inch of height:

    Inuits don’t live longer even if they do not get heart disease as much:

  4. You are still ignoring that the population map and the heart disease map mesh far more poorly than the KFC and heart disease map. California, Florida, and the notheast have very high population and lower heart disease. While Lousiana, Mississippi, Oaklahoma and such do not have high populations, but very high rates of heart disease and KFC visits.

  5. Eh, I had a real “cough drop” beard in college. (I looked like Andrew Smith of the Smith Brothers.) I didn’t find it particularly required much maintenance. A little snipping once a week, and that was it.

    Not a fashion statement, though: I attended Michigan Tech in Northern Michigan; The beard kept my face from freezing, and provided a convenient place to store pens and pencils.

    You can see that Aubrey is putting basically no time at all into trimming his beard.

  6. Yes, they say low levels of lead which are concentrated in cities because of the exhaust that has spewed out for decades before lead was banned and the heavier traffic and such.
    But clearly the south does not have more traffic or lead than Los Angeles.
    Although, Louisiana did or does have a large lead smelting plant. But the impact of that would be fairly local as lead tends to fall out of the air onto the soil because of its high density. Maybe 50-100 miles.

  7. Ah, no, you mistake my point: Living at high population densities is, itself, known to be unhealthy. For a variety of reasons; It’s stressful, pollution tends to be worse, disease propagates easier. Cities have been population sinks for all of human history because of this.

    Thus anything that happens to be correlated with population density ends up correlated with mortality, even if it doesn’t itself cause mortality.

  8. The black dots on the KFc map are KFC locations, not super high numbers of visits. The green and blue are the indicators.

  9. The heart disease death rate is per 100,000 thus population density is controlled for.
    And the smoking one is the percentage of people smoking. That has nothing to do with how many people live in each county.
    Our population is not heavily in the south, KFC and heart disease is.

  10. No, creative cooks do, too. Every cook who isn’t actively trying to avoid generating AGEs is going to be exploiting the Maillard reaction. It’s why you brown your meat before stewing it, for instance, or caramelize vegetables. AGEs just taste good.

    There IS a significant difference between endogenous and dietary AGEs; The former represent modifications to structural and functional proteins in your tissues, and cause negative effects by stiffening the intercellular matrix, disabling functional proteins, and accumulating due to failure of cellular cleanup mechanisms.

    The latter mostly don’t have these effects, but apparently do have some degree of toxicity in and of themselves. Mostly by triggering generalized inflamatory reactions, apparently.

    I tend to think we would be better off improving the body’s response to these substances, rather than trying to rigorously avoid them. As long as our metabolisms rely on sugar, you can’t entirely avoid AGEs.

  11. I’ve about concluded that it’s time to talk to my doctor about getting a metaformin prescription; I can probably swing it, my fasting blood sugar has been creeping up, although my A1C remains low, so I’ve got a conventional excuse for it.

  12. Wait, you’re saying people get tatoos and piercings becuse they’re ugly and want to take themselves out of the beauty pool all together?

    While you are right tatoos and espically piercings are more detractive than actrative to the average person.

    Your reasoning flys in the face of reality, for if what you said is true then why the heck are there so many attractive women with tats and piercings?

  13. As someone who has a beard, a short one is minimal effort but once it gets a bit longer the care required starts to go up again.

    Just ask someone with long hair if it is less work than short hair.

  14. I have seen other articles that were quite compelling, but I think it is sufficient to have a look at what have the highest levels and ask yourself, are these healthy foods? : bacon, butter, fried meats, processed meats, mayo, cheese…

    Then there are the high numbers in olive oil and canola. I am betting the benefit of olive oil are due instead to the antioxidants that are more prevalent in extra virgin olive oil. And I have my doubts about canola.

    Heart disease rates have come down since everyone started eating olive oil and canola oil, sort of. The olive oil boom preceded the gains so is not likely to be the cause:
    I think it is a better fit to look at the reduction in smoking:
    I think that is the real source in lower heart disease deaths.

    OMG I found two graphs that almost exactly match one another: KFC sales and Heart disease :
    And the bottom graph here:

    Fried chicken has very high AGEs. More than any other fast food.

  15. Endogenously formed AGE’s are harmful, they disable the function of proteins, and often disrupt cellular cleanup mechanisms. It’s not as clear that dietary AGE’s have harmful effects, because they don’t represent disabled proteins.

    According to this study, they seemed to, but the statistical confidence of the result was quite low. I think it’s not entirely clear yet.

  16. We already have life extension. The sick diabetics were outliving perfectly healthy people because they were taking metformin.
    And the study had a large number of people.

    And supplements available today may help as well. Like fisetin, grape seed extract, and alpha-lipoic acid. There is even stuff that can extend telomeres. Though mostly they act on the immune system and perhaps some of the cardiovascular system. Pricey stuff. Cycloastragenol and Astragaloside IV. I just take cheap Astragalus Extract, which may or may not do anything for telomeres. The Cycloastragenol and Astragaloside IV are only in some varieties of Astragalus. Not terribly concerned about telomeres yet. I want to clear out the senescent cells using fasting and fisetin. Doing this every 2-3 months. I am hoping to clear out most of it over say 5 years. Probably increasing the dose and adding more senolytics. Eventually, I would need it measured. If it was low then I will try to extend the telomeres.

    And we know know that HIIT exercise has benefits as does fasting. Strength training improves bone health. And, of course, good old cardio helps with cholesterol, blood pressure, sleep, brain health and a bunch of other things. Though overdoing cardio can promote free radical damage.

    If a boomer were serious and dedicated, I see no reason they could not make a sizable improvement in their health and longevity starting today.

  17. I think he is just trying to be efficient with his time. He has priorities. And he is likely pleased with the efficiency he has achieved, and does not give a hoot, if people are not impressed with his style. He has things he wants to get done as soon as possible.
    I do think he is hurt when people say he looks old. There is no need for that.
    He also has established recognizability, which can be important to funding and such. Though I doubt that was the initial goal.

  18. I think reengineering people can make them live much longer, and without many changes. Bowhead whales live to at least 211 years. They do this by having a lower body temperature..92.8F. Their closest relative has our identical temperature and lives to low-mid 70s…very similar to us. When the temperature is lower all sorts of destructive chemical reactions are reduced including most of the ones we call aging. We are at the temperature we are at because our enzymes are optimized for that tight range. But we could borrow the genes for the enzymes from other species like the bowhead. Doesn’t do anything for living people, but future people could live quite long.
    They could be further engineered to make vitamins in their bodies at optimal levels. The liver would not need to store A, D, E and K, and could perform other roles better. These people could have the same modification the mice had enabling the complete removal of senescent cells, maybe something to trigger a periodic recycling of mitochondria, and a periodic telomere extension. And there are all the identified genes that can make people live longer and reduce their susceptibility to various aging diseases. No reason we could not make those modifications as well.

  19. What I am hoping for is to “inhibit AGE formation” and eat less of the stuff. I am also hoping that by just having less of these in my system my kidneys will be faster and more effective at removing what does absorb or form in my body. I am not really expecting the supplements to help the break down much.

  20. I think you’re missing the point there. The train of logic is as follows:
    [1] I’m not going to win the conventional beauty race. I can tell because I own a mirror.
    [2] BUT that’s not the only game in town. There are so many people with bizarre tastes out there (see Internet, Rule 34 of) that I’ll find at least a few fans providing they notice me.
    [3] Therefore, I pick a look that is not conventionally beautiful, and do it real hard. Sure 99% of the population are turned off, but I probably wasn’t going to win with them anyway, after all only need to find appeal to 1% to look amazingly hot to 3 customers per day (assuming a 300 cup/d barista job).

    Of course not everyone has the intellect or introspection to actually go through that logic chain, some just copy what their friend Bob does. Bob copied Jo. Jo does the thinking in that circle of friends.

  21. The greatest thing about this research is that the technology to combat all these forms of aging won’t be widely available until after the boomers have aged out.

  22. I have learned to cook with spices, and healthy flavorful things like pimentos. I have got just about every spice. People swipe my pomegranate juice, orange juice, celery, and eggs, but my tofu, parsnips and butternut squash don’t need LoJack.

  23. Nice try. If you become suicidal without bacon, microwaved bacon has 1/10 as much AGEs though still high. Pan fried bacon is 91,577 AGE kU/100 g. For some reference, butter is the second worst food and it is at 26,480 AGE kU/100 g, so pan fried bacon is just at another level. Microwaved 9,023. Any meat over about 5,000, I think is iffy. But, maybe if you don’t have much and everything else is healthy…
    Forget butter and butter substitutes including cream cheese. Avocado would be just fine on toast.
    I eat my toast dry. I don’t miss the butter at all. OK, I miss it with artichoke and yams. I don’t buy English muffins. That would be torture.

  24. I don’t know if you are trying to concern troll, but enzymes to break glucosepane have already been found:

    “Identification of Glucosepane Cross-Link Breaking Enzymes

    Glucosepane is a member of the class of advanced glycation end-products (AGEs), which form non-enzymatically in the human body. Glucosepane, is the most abundant AGE found in human collagen and has been implicated in the pathophysiology of various conditions ranging from diabetes to normal human aging. Glucosepane crosslinks impact the structural and mechanical properties of collagen and contribute to stiffening of collagenous tissues and vascular dysfunction. We have previously demonstrated the total synthesis of glucosepane, enabling methods for detecting and targeting glucosepane. The present study seeks to identify enzymes that are capable of catalyzing the decomposition of synthetic glucosepane crosslinks. To identify glucosepane crosslink breaking enzymes, we developed a novel screening technology based on metagenomics….”

    The hold up to finding glucosepane breaking enzymes was always actually getting enough of it, but it can now be synthesized.

  25. Even cyclodextrans to remove oxidised Low Density Lippoprotein would be nice, heart attacks and strokes are still right up there as causes of death and suffering.

  26. In a strategy of optimal reproduction of our ADNs (we are the puppet of our ADN! when the ADN has accomplished it’s mission, he does not need our body anymore: “he” can program the destruction our body to preserve ressources . See an excellent book in French: “biologie de la mort” )
    I think that any external / visual signs of deterioration of our physical condition should be carefully observed. Those signs are shouting to all others around: “hey! avoid reproduction with this body, it was too damaged”.
    It is interesting to notice that the follicles generate hair and color or pigment cells that contain melanin. Over time, hair follicles lose pigment cells, resulting in white hair color. This process is accelerated by oxidative stress and others damages.
    Well, to date we know **no way** to reverse this process. And as an end marker of our age, I think that the research of anti-aging strategies, at an holistic level, should be connected to / cover all routes related to those visual markers.
    I’m surprised that this aspect seems to miss into the presentation of Aubrey above.

  27. One of the these that I have actual research experience with – carnosine – does indeed break AGE crosslinks – the issues are:
    (i) by that time the proteins are denatured & breaking the crosslinks produces smaller versions of denatured proteins
    (ii) the byproducts are often aromatic => coloured substances with reactive groups that can further oxidize / precipitate further crosslinks & at a greater rate b/c they are smaller

    I think the solution lies in preventing the AGEs to begin with – to that end you need to strike a balance b/w oxidation / inflammation as a mechanism for removal of debri vs as a mechanism for repair

    I think the answer lies in genetics – i.e. determine the genes responsible for stricking this balance => we can live to reach the 100-120 age group.

    Beyond that I think is wishful fantasy (at least as far as I can see into the future)- I’m placing all my bets with cyborg / synthetic augmentation / transference rather than organic – assuming you wish to occupy an individual body vs mind in cybserspace scenario

  28. I really, really don’t like judging someone’s science on the basis of their fashion sense.

    But you’re right.

    In the sense that he is acting as a spokesman for anti-aging, then as a spokesman, your presentation is actually a vital aspect of your credibility, and looking like a bit-character from Lord of the Rings doesn’t help at all.

  29. Rules of thumb:

    1. Anything cooked/roasted at high temperature will likely have elevated levels.
    2. Anything whipped or beat thoroughly that has any oils will likely have elevated levels: butter, mayo, peanut butter…
    3. Cheeses are high: reduced fat cheese is fine, Parmesan is worst
    4. Soups are terrific
    5. Any oils are going to have higher levels than other foods. Making the best oil choices will make the largest difference. Corn and non-toasted seed oils are best. There is reason to believe Avocado oil and pistachio oil are good too. Olive oil, and canola do not have good numbers.
    6. Cereals, breads as long as you don’t toast much are fine…except rice crispies. No cookies, no granola bars.
    7. Fruit is fine except fried figs
    8. Beverages are fine except the meal drinks: Glucerna, Resource (Nestle), Enfamil
    9. Bacon is the worst possible food!
    10. Frozen waffles and pancakes are not good. Make them yourself and they’re fine.
    11. Most roasted nuts/seeds and nut/seed oils are not good
    12. Raw nuts are OK except pine nuts
    13. Fried anything is bad
    14. Stews and chilies are good as long as you don’t burn it.
    15. Acidic sauces around your meat while cooking can protect to some degree.
    16. The more you eat your carbs, fats and protean in ways where they are not blended violently or cooked after being mixed, the better.
    17. Boiling your meat is best even if it is only in a little water.
    18. Meat in general is a bit high

    Heavy cream is ok, but butter is the second worst food possible. The beating/whipping is what destroys it.

  30. Went out and looked into this.

    Says the average for Americans around New York is 15k dAGE, and that 20k might be high and 10k might be low. Methods of cooking really changes things and sadly, the way I like things cooked is mostly the wrong way (and the wrong foods, to some extent).

    But then I read this:

    A safe and optimal dAGE intake for the purposes of disease prevention has yet to be established. However, in animal studies, a reduction of dAGE by 50% of usual intake is associated with reduced levels of oxidative stress, less deterioration of insulin sensitivity and kidney function with age, and longer life span.

    And it struck me that, for those of us that fast every other day, we ARE cutting dAGE by 50%, providing we don’t go crazy when we do eat.

    Still, this “eating right” stuff is getting awfully complicated.

  31. Yes. It is more common because the body can’t eliminate it. The others do get broken down if your kidneys work well and other stuff. Glucosepane just accumulates. I think they have found some things that can break it down. They need to screen them to find safe candidates for testing. Maybe in another 5 years we will at least know the names of the potential glucosepane breakers. Another 5 years after that…maybe.
    It is harder to do this testing in animals as the AGEs they have don’t include glucosepane or only in very small amounts. We probably will have to engineer mice/rats that make a bunch of this crud to see if we can eliminate it in an animal model.
    My plan in the interim is to make as little of this as possible by eating low AGE foods, and taking supplements that reduce the formation of AGEs.
    “Compounds that have been found to inhibit AGE formation in the laboratory include Vitamin C, benfotiamine, pyridoxamine, alpha-lipoic acid,[34]taurine,[35]pimagedine,[36]aspirin,[37][38]carnosine,[39]metformin,[40]pioglitazone,[40] and pentoxifylline.[40]”
    Of these, I take: Vitamin C, benfotiamine, pyridoxamine (AKA P-5-P), alpha-lipoic acid, taurine, carnosine, and metformin.

  32. We need AGE breakers now! They would go a very long way to increasing healthspan if not lifespan. If you make a safe breaker of glucosepane you are an overnight billionaire. This one AGE molecule is 10-1000x more common than all the others.

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