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.
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.
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.
Even if let's say, the average longevity does not change, it would still be a game changer if you could be as healthy in your 80s as in your 70s. Agree that nobody wants to live to 100 while being strapped to a hospital bed the whole time.
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.
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.
> 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.
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.
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."
> 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.
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.
That could get complicated fast. Imagine ten thousand copies of your brain, all with different ages, experiences, and opinions, deciding what to do with your money, how to educate your children, what kind of relationship you want with your spouse.
Romance could get complicated for monogamous people. Polyamorous partners would negotiate new agreements about duplicates. Marriage as an institution would probably dissolve due to impracticality; it would be equivalent to a series of divorces and remarriages with each duplication, and two-partners-per-marriage would be a weird constraint.
Resource constraints are certainly an issue; the fairest way seems like pre-allocating a subset of resources to each duplicate who in turn can do the same. Societal restrictions on creating a duplicate with too few resources would prevent effective slavery or abject poverty.
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)
> I find it funny how people believe a simple molecule made from a dozen atoms is somehow the elixir of immortality
That's a weird statement to make, while in the largest part of the 20th century, most medicinal advances were made using small molecules. Aspirin is a very potent drug that had dozens of actual applications at least, yet remains a very simple molecule.
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.
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.
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.
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.
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.
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
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.
Sure, I'd be happy to share, but this is just an opinion.
Secure an appointment in a genetics clinic at a world-leading institution - think the sorts of hospitals that routinely see the rarest genetic diseases in the world, CHOP, CHLA, Rady in SD, Emory, Children's Boston, Lourie in Chicago (the children's hospital, not the cancer center), Nationwide in Columbus, Hopkins, etc. Ideally you'd be seeing someone who is continually identifying and publishing newly discovered genetic diseases.
Compose a short, concise document detailing developmental milestones as well as symptoms. Include all interventions that you have found to work and not work. Include all prior test and imaging results. This document will be given to the geneticist and genetic counselors you meet with. You can also look into having the medical record transferred over from the primary care facility to the geneticist's office.
Let them handle the rest. They may recommend testing, they may recommend consults with additional specialists, they may feel the issue is not genetic. It is important to keep in mind that one does not need to be far outside of the box to butt up against the limits of medical knowledge. It is possible that this strategy may not help. There are also research programs, such as the undiagnosed disease program at the NIH, that may also be potential avenues to pursue. It is also possible that the issue does not have an identifiable genetic cause, or if there is, the underlying pathology is currently not understood.
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.
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?
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.
> 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
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?
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.
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.
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.
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.
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.
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
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.
Look, I absolutely encourage questioning religion and the Bible, but this particular hill is not one I suggest you die on.
Genesis chapter 11 (allegedly) recounts the lineage of Abram. Shem (who was on the ark) lived to be 600. His son Arphaxad lived to be 438. HIS son (Shelah) died at 433. Et cetera. Abram is only eight or nine generations after the Flood, depending on how you count.
To my eye, there's a clear dampening effect on ages after the Flood. Within a dozen or so generations, mostly everybody dies before age 120.
Some of us have actually studied the Bible in depth. It has its contradictions, but IMO this isn't one of them. :)
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
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.
> 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.
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.
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.
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).
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.
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
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.
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
- 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/