[HN Gopher] Analysis of blood markers predicts human lifespan limit
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Analysis of blood markers predicts human lifespan limit
Author : Kinrany
Score : 202 points
Date : 2021-05-26 10:51 UTC (12 hours ago)
(HTM) web link (www.nature.com)
(TXT) w3m dump (www.nature.com)
| legostormtroopr wrote:
| Now if only they could convert this into some sort of death
| clock, that would put those young whippersnappers in their place.
| inglor_cz wrote:
| GrimAge to your service:
|
| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6366976/
| arisAlexis wrote:
| There is no known limit. Just the notion of knowing the limit
| while we don't know how our body works 100% and while some other
| animals don't age is just silly and not scientific at all.
| apalmer wrote:
| I don't understand this statement? No human we are aware of in
| the history of the world has lived to 130. That's a pretty
| scientific known limit.
| grishka wrote:
| This assumes that the organism will age naturally and that no
| interventions will be done to influence that process.
| bryanrasmussen wrote:
| what interventions would lengthen the lifespan given these
| markers?
| elliekelly wrote:
| I have no idea if/how relevant this is but I read this really
| interesting article[1] yesterday about naked mole rat aging
| and how they're being researched to identify possible anti-
| aging interventions for humans. It's not exactly a science-
| heavy article, though, if that's what you're looking for.
|
| [1]https://www.wired.com/story/long-strange-life-worlds-
| oldest-...
| grishka wrote:
| After reading some research papers, especially the ones about
| heterochronic parabiosis (when they connect the circulatory
| systems of a young and an old animal), it feels to me like
| "markers" is a kind of misnomer. They aren't markers, they
| aren't just _signifying_ something -- they 're what drives
| the aging process in the first place, in a feedback loop. You
| can't explain those experiments otherwise. These, and also
| that when you transplant an organ from an old animal into a
| younger one, the organ adopts the age of its new host. There
| has to be something in the blood that tells the cells the age
| of the organism, and the cells then adjust their behavior
| accordingly.
|
| So, the question becomes: what if instead of merely observing
| those markers, we actively remove them, or block the
| receptors they interact with?
| f38zf5vdt wrote:
| That part is easy, the hard part is not causing cancer when
| doing so. For example, cancer cell lines often have lots of
| telomerase activity. The creation of immortal human cell
| lines through site-directed mutagenesis is easy, since we
| know most of the genes that promote cellular immortality
| from studying cancer.
| jolux wrote:
| Isn't the body hostile to cancerous cells too?
| f38zf5vdt wrote:
| Up to a point. Cancer is the result of multiple mutations
| to growth regulation genes and immunogenic factors that
| collectively lead to immortal cell lines that are able to
| evade the immune system. The more mutations you introduce
| to try to immortalize your cell lines, the closer they
| get to becoming pathologically cancer.
| grishka wrote:
| For cancer, there's other research. Google Michael Levin
| and his morphogenesis research. In short: when an
| organism grows, it needs to store the intermediate state
| of its growth somewhere (in the same sense that you have
| a counter and an end condition in a for loop), and cells
| need to communicate somehow to coordinate their division
| and specialization. That somewhere is in electrical
| potentials between cells. He came to a (sensible)
| conclusion that cancer occurs when a bunch of cells falls
| out of this network. And indeed, he was able to induce a
| tumor in a tadpole, and then make it go away by
| "plugging" these cells back into the network. It's really
| fascinating and a bit creepy.
| johndoe42377 wrote:
| Oh, really? And how exactly they tested their predictions?
| jyu wrote:
| If you're new to this area of biomarkers and longevity, there are
| several people to follow with different approaches:
|
| - David Sinclair Why We Age and Why We Don't Have To. Mostly
| focused on NAD+, sirtuins, use of yamanaka factors to reset
| epigenetic clock
|
| - Horvath for horvath clock using dna methylation to measure
| aging in organisms.
|
| - Michael Lustgarten a good curator for biomarker related
| research for longevity
|
| - Rhonda Patrick has insightful scientific interviews and dietary
| and behavioral interventions
|
| There's a spreadsheet with 9 biomarkers (with correlations) and
| age for Levine's Phenotypic Age floating around, based off this
| paper: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5940111/
| aantix wrote:
| How does Horvath measure DNA methylation?
| [deleted]
| zemvpferreira wrote:
| By running your blood through a specific DNA methylation test
| - Illumina I believe. Not cheap stuff.
| aantix wrote:
| Strangely, my son who is six, who has exhibited symptoms of
| schizophrenia and has been formally diagnosed with ODD
| (oppositional defiant disorder), responds incredibly well
| to a combination of Niacin/Magnesium.
|
| He becomes a different person when he has taken his
| vitamins for the day, a more caring person. It's been a
| profound transition, and one that we didn't expect. We had
| tried everything - improving sleep, improving diet, weekly
| behavioral therapy. Nothing has come remotely close to the
| impact that the Niacin/Magnesium combination. It's probably
| a 70% improvement in behavior. That dramatic.
|
| I stumbled across the works of Abram Hoffer. That this is
| probably an issue related to overmethylation within his
| system, and the B3 helps subside this issue. At least my
| very basic understanding. I know I am trivializing the
| domain - I don't mean to.
|
| Not sure how to confirm that overmethylation is the issue,
| hence why I was asking. Thanks for the insight.
|
| P.S. For those curious, this is the current protocol of
| vitamins we have been using to help him.
|
| https://aantix.medium.com/my-son-niacin-magnesium-and-the-
| tr...
| zemvpferreira wrote:
| That's amazing, it would definitely be a good investment
| to get as much data on his DNA as possible. A definite
| diagnosis will certainly have a huge impact on both your
| lives and your relationship.
|
| Thank you for sharing your specific protocol by the way,
| I was about to ask. I've tried Magtein before but nothing
| like the doses you describe, and never paired with Niacin
| goldenkey wrote:
| Magnesium can cause stomach cramps and liquid shits. I
| hope you are monitoring this thorny effect..
| aantix wrote:
| Very aware. I get that periodically with glycinate.
|
| l-threonate is much lower dose of elemental magnesium,
| usually 144mg, but it's much more targeted.
| goldenkey wrote:
| Glad to hear it. L-threonate is actually what I had
| tried, and it caused the issues for me. Just constant
| "pudding poops" every time I took it. And I did the Rogan
| method of sandwiching the dose in the middle of a meal,
| so it would be around food in the stomach. Didn't help. I
| wanted to use it for its mental effects (depression and
| sleep issues), but unfortunately the stomach interference
| prevented me from ever using magnesium again. If you have
| any recommendations, I'd be happy to hear them. I hear
| such rave reviews about magnesium from so many people.
| abcc8 wrote:
| While DNA methylation may be involved in the specific
| pathology you mention, it is by no means definitely
| involved. Both Magnesium and Niacin are cofactors
| utilized by many enzymes and their supplementation are
| likely having pleiotropic effects.
|
| *Edit: Added a mistakenly omitted word.
| zemvpferreira wrote:
| Direct link to Illumina's page on methylation:
|
| https://www.illumina.com/techniques/popular-
| applications/epi...
| aantix wrote:
| The test looks fascinating. It sounds exactly what is
| needed.
|
| I am just wondering about my capability to interpret it
| correctly within the context of my son's symptoms. I
| wouldn't want to wrongly diagnose him.
| JamesBarney wrote:
| The evidence for sirtuins is pretty good. Probably the first
| drug we find that extends life span in humans is going to be
| metformin or rapamycin.
|
| NR and NMN have failed to extend lifespan in rats, so it
| probably doesn't work with humans. (I don't know anything about
| yamanaka factors.
| Bellamy wrote:
| I read Sinclair's new book Lifespan and saw Patrick in a
| podcast. I got really excited and installed the Habinator app,
| because it's all about the lifestyle and habits until we get a
| breakthrough how to fix our bodies using pills or whatever.
| PudgePacket wrote:
| There's a lot of interesting people in this space
|
| Many I've discovered through this podcast, which features a
| number of people on the above list as guests:
| https://peterattiamd.com/podcast/
| andy_ppp wrote:
| Both David Sinclair and Rhonda Patrick seem to be getting
| younger ;-)
| mikevm wrote:
| I don't take Rhonda Patrick seriously anymore. After using her
| Genome Analysis Tool and reading some of the reports I saw that
| some of the studies she cited in fields I have some knowledge
| in (nutrition) were known to have methodological issues. She
| also tends to cite a lot of animal studies, while we pretty
| much know that they're good for generating hypotheses and
| further studies and may end up being completely useless for
| humans.
| johndoe42377 wrote:
| If you don't mind, why exactly these speculations are qualified
| as a science (which implies reproducebility of results)?
| PragmaticPulp wrote:
| Longevity research had been fun to follow, but I'd caution
| newcomers to take everything with a grain of salt.
|
| The field of longevity influencers has exploded recently, with
| increasingly confident claims extrapolated from preliminary
| research and hypotheses.
|
| Some of the longevity influencers, including some of the people
| in the list above, have significant financial interests in
| promoting their theories and methods. This ranges from selling
| educational materials to speaking engagements and even
| promoting supplements. As is typical with cutting edge
| research, the confidence of certain claims tends to be
| exaggerated when a financial conflict of interest becomes
| involved.
|
| A few years ago the longevity world was all about resveratrol
| after some promising early research, though later research
| suggests that resveratrol isn't quite as miraculous as it was
| initially promoted. We're currently going through a similar
| cycle with NR/NMN supplements like Niagen.
|
| There may be some promising developments in this area, but I
| wouldn't rush out to spend money on expensive supplements that
| haven't been tested at high doses long term in humans just yet.
| Longevity influencers like to talk about the potential upsides,
| but they rarely admit the unknown potential downsides.
| PaulHoule wrote:
| I think it not interesting news that "substance X extends the
| life of rats", or "substance Y might extend the life of
| yeast."
|
| Humans are exceptionally long-lived animals that live for
| about 4x as many heartbeats as other mammals. It is one thing
| for treatments to give animals some of the resilience to
| aging we have, it's another to extend the frontier of human
| lifespan.
| mrwh wrote:
| Agreed. And the low hanging fruit has already been plucked:
| improving infant mortality, basic hygiene. My grandparents
| all lived well into their 80s/are still alive.
| Realistically speaking, I doubt I'll do much better.
| vletal wrote:
| TBH I'd rather die happy around the age of 75 than
| miserable at 90+ like my grandparents.
|
| Not everyone has the luck of being cared of as British
| Queen and Prince were, yet they seem to die anyway.
| jostmey wrote:
| You nailed it. I find it funny how people believe a simple
| molecule made from a dozen atoms is somehow the elixir of
| immortality, as if aging is a simple biological process that
| we can flip off with a single switch.
|
| If we want to take aging seriously, we need to first
| appreciate the problem. It reminds me how people used to
| think there was "the cure" for cancer.
| RosanaAnaDana wrote:
| :entropy has entered the chat:
| jerf wrote:
| Personally, I have a hard time guessing which of "extend
| the life of the human organism to, let's say, 500 years" or
| "read out the living brain state of a human being and
| simulate it in a computer" is going to be easier. With full
| knowledge of how hard the second may be, if indeed it is
| possible at all.
|
| I wouldn't be surprised there's a few "One Weird Trick to
| Extend Your Life by Five Years"s yet to be found, but to
| _solve_ aging I expect to be much harder. It wouldn 't
| surprise me much that the simplest "solution" to aging
| could end up being the brain simulation thing anyhow,
| because fixing up the biological organism across hundreds
| of years is simply that hard.
|
| If there _are_ a few of those weird tricks I _definitely_
| expect a period of excessive optimism where people conclude
| we 're just another couple of such tricks away from the
| solution, when instead they are simply the first steps on a
| very long path.
| the__alchemist wrote:
| If you're interested in Sci-Fi on the topic, Charles
| Stross's Accelerondo, and Neal Stepheonson's Fall; or,
| Dodge in Hell are excellent.
| benlivengood wrote:
| > Personally, I have a hard time guessing which of
| "extend the life of the human organism to, let's say, 500
| years" or "read out the living brain state of a human
| being and simulate it in a computer" is going to be
| easier.
|
| The latter is probably closer. We can already induce
| extended periods of apoxyia in animals by replacing blood
| with cold saline without brain damage so a similar
| procedure should be possible to keep healthy brain tissue
| intact while scanning it. The necessary fidelity of the
| simulation is what we don't know yet.
|
| Keeping a human being alive for 500 years means knowing
| how to do roughly the same thing to bodies in order to
| accomplish the major periodic surgeries necessary to
| replace failing/injured parts including healing the brain
| itself, so probably represents a harder technical
| threshold.
| scarby2 wrote:
| However brain simulation isn't on a par with life
| extension. with brain simulation you still die. You're
| just replaced by something extremely similar to you with
| all your memories. There's a distinct break in
| continuity. At that point i can just create clones of my
| consciousness, the original consciousness does not want
| to stop existing.
| messe wrote:
| It depends on what you consider to be you, and whether
| continuity of consciousness is important to you
| personally.
| benlivengood wrote:
| > You're just replaced by something extremely similar to
| you with all your memories.
|
| That happens every night I go to sleep and a fair portion
| of my atoms get swapped out by normal metabolic
| processes. My neural network changes as I'm unconscious
| or dream. I don't even remember all my dreams, but wake
| up with new thoughts/ideas sometimes.
|
| We're always some delta from ourselves the previous day.
| I'm very different from the me of 10 years ago. The jump
| to a brain simulation may be a large change, but I could
| also tweak the things that didn't feel quite right or
| match with what I used to be like.
| shard wrote:
| The difference is that you cannot meet face to face with
| the delta you from before you went to sleep, thus all
| rights and privileges reside within one continuous body
| through time. It depends if you are comfortable with
| having an extremely similar copy or multiple extremely
| similar copies inherit all your rights and privileges.
| benlivengood wrote:
| Legal rights would probably be an AND situation rather
| than an OR, or maybe some sort of majority-rule
| situation.
| piercebot wrote:
| This idea is explored in Walkaway: A Novel, by Corey
| Doctorow. If you enjoy reading fiction, I highly
| recommend it!
| vvillena wrote:
| It's also a big concept in the Revelation Space series by
| Alastair Reynolds.
| SiVal wrote:
| Scenario 1: You go to sleep, they copy the info, you wake
| up in a new, young body. "Wow! This is great. When this
| body gets ten years older, I want to do that again!" They
| turn off the old body as you do your happy dance.
|
| Scenario 2: Same as 1, wake up in new body, etc. But they
| also wake up the old body. "Hey, I thought I was going to
| be in a new body!" They point at the young "you" doing a
| happy dance. "We just wanted to show you that it worked.
| Congratulations. Now lie back so we can deactivate you."
| The other one stops his happy dance: "Let's forget about
| that update ten years from now."
| [deleted]
| munchbunny wrote:
| _I find it funny how people believe a simple molecule made
| from a dozen atoms is somehow the elixir of immortality_
|
| We've absolutely been here before with vitamins, both the
| fact that they're simple molecules and part where we over-
| promise what they can do. (Example: vitamin C mega-dosing)
| subsubzero wrote:
| Agree, I feel like the best way to feel great and age well is
| not taking thousands of pills, but through classic healthy
| steps, not really sexy but they have worked well for many:
| get enough sleep, eat healthy, exercise alot, avoid stress.
|
| Looking at long life proponent Ray Kurzweil, he takes one
| million dollars of vitamins and supplements yearly and looks
| alot older than his age. He seems to be wearing a wig lately
| which makes him appear a bit younger but I think his
| supplement regime is big waste of money.
| nradov wrote:
| Recent research hasn't produced any convincing evidence that
| NR/NMN supplements will extend life. However there may be
| some other small health benefits for certain people.
|
| https://peterattiamd.com/does-nmn-improve-metabolic-
| health-i...
| erdevs wrote:
| Thank you for the link to this paper, as I'd looked for it
| previously and somehow didn't find.
|
| Do you happen to have a link to the spreadsheet handy too?
| Thank you, if so.
| highenergystar wrote:
| I can't vouch for it's accuracy, but here is a 'phenoage'
| calculator I came across while chasing down this rabbithole
| (after reading the paper) a couple of days ago
| https://www.oliverzolman.com/phenoage-calculator
| byproxy wrote:
| Cells G41 and G42 show as empty for me. G42 is referenced in
| the F42 equation, so it not being there seems to break things.
| mthwsjc_ wrote:
| I haven't read the complete paper, only the abstract, but it's
| fascinating to me that the authors find a limit of 120 to 150
| years.
|
| I remember reading in Genesis (first book of the bible) that the
| maximum age was limited to 120 years (chapter 6, verse 3).
| tomrod wrote:
| While very old, Genesis' stories were told by bronze age folks
| to each other and by an area's local priests for a variety of
| reasons, much like stories of Odin, Thor, Ea, Zu, Zeus, and
| Neptune. A broken clock may be correct twice a day, but I
| wouldn't take it a proof that the clock is predictive
| sometimes.
|
| Indeed, the stories of Enoch and Methuselah show that any hard
| bound was clearly violated within a tiny group of humans it
| claims are originators.
| arbitrage wrote:
| > the stories of Enoch and Methuselah show that any hard
| bound was clearly violated
|
| you're taking things a little literally here; that's
| perfectly explainable, and is also paralleled in the other
| mythos you mentioned: a group of people would raise their own
| status by claiming to be descended from gods or demi-gods or
| something else extraordinary. Probably the most approachable
| example of this in western literature is the figure of
| Herakles/Hercules.
|
| it is not a stretch to imagine that the people responsible
| for writing certain books of the hebrew bible raised their
| own status by claiming to be descended from extremely long-
| lived ancestors.
|
| Additionally, methusaleh's obtained age was recorded as 969
| years; this should be understood not literally, but
| figuratively: 969 is a looooooong time, and a mystical
| number. It means "this is important, pay attention to this.
| this person is special". It helps the narrative in an oral
| tradition.
| TeMPOraL wrote:
| Alternatively, you could notice that the abnormally-long
| lifespans match a pattern of exponential decay towards a
| new equilibrium. This would be consistent with a hypothesis
| that there was a lifespan-extending factor involved, which
| effects grew weaker from generation to generation. The
| factor could perhaps have been environmental, or genetic.
|
| I don't subscribe to this view, because I no longer believe
| the stuff described in the Bible actually happened as
| described - but if I were trying to treat the Genesis
| stories as real, this would be the approach I'd take to
| reconcile them with scientific knowledge.
| raducu wrote:
| Or some decaying that reduced lifespan and made marrying
| your close relatives not ok :)
|
| But I don't think there's any point trying to reconcile
| the naratives.
| teach wrote:
| > Methuselah show[s] that any hard bound was clearly
| violated...
|
| Not quite. Methuselah died in the Flood, and it was only
| _after_ the flood when God decreed that humans' lifespan
| would be limited to 120 years.
| vmception wrote:
| Were years even the same kind of years?
|
| 2000 years ago but even the King James Version wouldn't have
| been using a gregorian calendar yet
|
| And usually when talking about the Bible there has some greek
| or hebrew translation liberty
|
| Before we all decide it's open to interpretation anyway
|
| Well I had your whole conversation for you, let me know
| kaikai wrote:
| A different calendar doesn't necessitate mean a different
| year length. We still measure a year as a complete solar
| cycle, and that hasn't changed.
| vmception wrote:
| There are many nuances in how a year is and was
| determined
| _ZeD_ wrote:
| "nuances" as in ... seconds? minutes? days?
| vmception wrote:
| The Roman calendar was just a lunar month times ten until
| being fixed to a solar year around like 500 BC
|
| I don't know if there are retroactive fixes to what years
| were which and if that coincides with the Bible or
| universal acceptance of their solar calendar
|
| Let me know
| rootusrootus wrote:
| > Roman calendar was just a lunar month times ten
|
| Plus the winter, which was unassigned until it eventually
| became January and February. I don't see anything about
| it counting the entire year as anything other than a
| solar year.
| _ZeD_ wrote:
| yes, years were the same... keep in mind that "year" (but
| also "season") were of the most importance for agricultural
| people.
| canadianfella wrote:
| And Eve is a McRib.
| FiReaNG3L wrote:
| There's a lot of numerical symbolism in the bible, and 12 or
| powers of 12 (144, etc) really means 'a lot'
| timbit42 wrote:
| The reason for the twelves is that the numbers were
| incorrectly translated from cuneiform into Hebrew. Sumerians
| used 12 and 60 (5x12) in their numbering systems, thus modern
| clocks have 24 hours and 60 minutes, and circles have 360
| degrees. If you translate the numbers back into cuneiform and
| then correctly translate them again, the ages are all similar
| to the ages people live today.
|
| Source: Noah's Ark and the Ziusudra Epic: Sumerian Origins of
| the Flood Myth by Robert M. Best
| timbit42 wrote:
| Genesis doesn't say people's lives are limited to 120 years.
| What it says is that the flood would occur in 120 years time.
|
| That said the numbers in Genesis were incorrectly translated
| from cuneiform into Hebrew. If you translate them back into
| cuneiform and then forward again correctly, you get smaller
| numbers that match up with the ages people have children or die
| today.
|
| Source: Noah's Ark and the Ziusudra Epic: Sumerian Origins of
| the Flood Myth by Robert M. Best
| melling wrote:
| Except people lived to be older than that in the Bible
|
| "Notice that Sarah lived to be 127 years (Gen. 23:1), Abraham
| lived to 175 years (Gen. 25:7), and Jacob lived 147 years
| before dying (Gen. 47:28)."
|
| https://www.neverthirsty.org/bible-qa/qa-archives/question/t...
| ARandomerDude wrote:
| All of whom are clearly portrayed in Genesis as being
| supernaturally sustained in their old age as exceptions to
| the rule (similarly, Moses and Joshua).
| melling wrote:
| The Dragon in My Garage
|
| http://people.whitman.edu/~herbrawt/classes/110/Sagan.pdf
| err4nt wrote:
| I also had read this verse as capping human lifespan to 120
| years, but someone pointed out to me that what may be referred
| to here is a duration of time before destruction of the earth,
| that might have been the countdown to the flood.
| siculars wrote:
| In the Jewish culture when someone has a birthday you say "ad
| meyah esrim". Which basically translates as "until 120". 120 is
| considered to be the max lifespan if not literally then
| certainly figuratively.
| braymundo wrote:
| In Polish it is "sto lat" (a hundred years). More
| pessimistic, it seems. :)
| inglor_cz wrote:
| Given the military history of Central Europe, it is
| actually very optimistic :)
| raducu wrote:
| The "comfortable" limit is set in Psalms to 70 years I think.
| huachimingo wrote:
| Wait, this is asuming that they have the same notion of a year
| as we have now.
|
| Unless some changes were made in modern translations.
| prewett wrote:
| What other notion of year would people use? There's clearly a
| repeating cycle of that takes approximately 360 days. The
| seasons cycle, the stars come back to their same spots. I
| don't think there is any evidence that ancient people used a
| different version of year. In fact, given that we still have
| Babylonian influences like 360 degrees in our circle, I'd
| argue that we have continued in _their_ tradition.
| strken wrote:
| Someone on the equator might divide the orbit of the Earth
| around the sun into two halves, a north-sun "year" and a
| south-sun "year".
|
| I have absolutely no evidence that any group did so, of
| course, but it wouldn't be totally absurd.
| vmception wrote:
| Very valid questions and I had asked the same
| laborat wrote:
| Not sure I understand the paper (not my field); are they saying
| that extrapolating from a mortality measure predicts that
| mortality is inevitable? If so... isn't that just a way of
| confirming the obvious, viz. that higher quantiles of a logistic
| distribution are closer to 1? Finding a cutoff age at a - quite
| large, it seems - number of 120-150 years is cool and all, but I
| don't see how this informs us about anything other than mortality
| measures predicting eventual mortality?
| toss1 wrote:
| It seems while the initial reading is that this is an
| inevitable process, the more sapient technological perspective
| would be that they've discovered a key mechanism that can now
| be investigated and adjusted for improved results.
|
| The key factor of humans getting to where we are (both good and
| bad), is our ability to see something that is, then figure out
| _why_ it is how it is, and then _change_ that structure
| /process/sequence to rearrange it to meet our goals.
| scarby2 wrote:
| > It seems while the initial reading is that this is an
| inevitable process, the more sapient technological
| perspective would be that they've discovered a key mechanism
| that can now be investigated and adjusted for improved
| results.
|
| I think this research is as much about to estimating the
| maximum age of an organism if all causes of premature death
| are removed. i.e. to get longer than that you need to fix
| aging itself not disease
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