Longevity is in the genes: half of lifespan is heritable (Nature)

#1

Understanding the genetic controls of ageing could lead to more therapies that forestall it.

Genetics has a much larger role in how long a person lives than previously thought, finds a new analysis that challenges decades of scientific consensus.

About 55% of the human lifespan is heritable, meaning that more than half of observed variation in longevity across a population is attributable to genetics. That is a far greater proportion than the 10%–25% previously estimated, according to the research, which was published today in Science 1.

The findings should aid in the quest to find specific genes involved in ageing and to develop treatments, says study co-author Ben Shenhar, a biophysicist at the Weizmann Institute of Science in Rehovot, Israel.

“There is much to be learnt from the genetics of ageing if we can understand what genes are responsible for healthy ageing,” he says.

Twin efforts

Shenhar and his colleagues say that previous estimates were far too low because they did not effectively separate deaths caused by extrinsic factors, such as infectious diseases or accidents, from intrinsic ones inside the body, such as the gradual decline of organ function stemming from DNA damage over time.

Read the full story here: Longevity is in the genes: half of lifespan is heritable (Nature)

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#2

No surprise here. It’s the inescapable conclusion one reaches looking at studies of centenarians and supercentenarians, as well as various health fanatics. If your body was only made for 85, then no matter how strongly you adhere to the very optimum of lifestyle, diet and exercise, at best you will fulfill your potential of 85, while the sloppy guy with bad habits will cruise to 105 because that’s what his body was designed for. This is why extreme exercise or diets strike me as bonkers if they come at the cost of QOL. Exercise and eat “well enough”, and leave the extremes to those who get a kick out of it, and you’ll get 99.999% if not 100% of the benefits anyway.

Our only hope at present, before genetic engineering comes along, is that a smart cocktail of drugs might push you slightly outside your body design - that’s where rapamycin and other drugs come in. They might, or might not work, ultimately. Right now we just don’t know, and we’re rolling the dice the best we can. YMMV.

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#3

How come you did CRON?

#4

CRON did not represent - at least initially any hardship. Hunger abated after a few weeks, and I really had no issues. I did it for a little over eight years. I ultimately gave it up not so much because of QOL issues as practicality - unless practicalities are cosidered part of QOL. I felt fantastic - better than at any point in life (including now). But it became very socially isolating. I couldn’t go out with friends to restaurants or invite friends for meals at home or go to theirs, or take long vacations, or easily meet with clients and collaborators (in my business lunch was obligatory - but now I’m retired from that). Shopping and food prep were a major hassle and a time (and mental energy) sink. Stuff like that. So I gave it up, though I maintain lowish calories to this day, from force of habit (and health considerations). In the end, I felt like it just was not a practical diet given my lifestyle and circumstances.

Btw. I took CR very seriously, which means I tried to do as good a job as I possibly could. Here’s an example of how that made it very hard socially: you can’t just sit in a restaurant with a salad if you’re on CR, or be around food period. Here’s why: research shows that the benefits of CR are abolished if you even smell food. This was intially established in flies. Look it up, it’s wild.

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#5

Wow that is wild - and seems to be support that at least some aspects at mechanistic level occur in humans too

https://scitechdaily.com/simply-looking-at-food-triggers-an-inflammatory-response-in-the-brain/

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#6

Apparently people in Loma Linda California have a median lifespan of about 90 (89 for males, 91 for females), and they have a pretty genetically diverse population, as I understand it (so, it’s not like they all have some magic genes). So, at least this shows that diet and lifestyle can get most people to about 90; and maybe a little more, like 95 or higher, if you try to optimize it (which I don’t think people in Loma Linda do) and throw in an optimal mix of pills like Rapamycin and various supplements.

The real gains will come when we get more radical methods, like greatly expanded anti-cancer therapies, perhaps mitochondrial replacements, and even tiny robots to repair the body.

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#7

Our lifespans may be half down to genes and half to the environment (New Scientist)

In wealthy, relatively safe countries, how long people live now probably depends just as much on the genetic variants they inherit from their parents as on their environment and lifestyles. That’s the implication of a study reanalysing data from research in twins in Denmark and Sweden.

For people living in these nations, it may be no surprise that their lifespans are probably half down to their genes and half to their environment. But earlier studies of the twin data, performed decades ago, concluded that genes explained only a quarter of the variation in human lifespans.

“It shifts the balance a bit, saying, OK, there’s a bigger role for genetics, while the environmental contribution becomes a bit smaller,” says team member Joris Deelen at Leiden University Medical Center in the Netherlands. “But at least 50 per cent is attributable to environmental factors, so environment still plays a major role.”

Full article: Our lifespans may be half down to genes and half to the environment (New Scientist)

Genes May Control Your Longevity, However Healthily You Live

A new study suggests that those with long-lived families probably have the best prospects of making it to a very old age.

Your potential life span is written in your genes, according to a new study. You can lengthen it a bit with a healthy lifestyle. But if your genetic potential is to live to be 80, for example, it is unlikely that anything you do will push your age at death up to 100.

That, at least, is the conclusion of a paper published Thursday in Science.

Uri Alon of the Weizmann Institute of Science in Israel and other researchers drew the data for the study from three sets of data from pairs of Swedish twins, including one set of twins that was reared apart. To test how generalizable the results are, the group also examined data from a study of 2,092 siblings of 444 Americans who lived to be over 100. Their goal was to identify outside factors that can affect how long someone lives, like infections or accidents, separate from the intrinsic factor of genetics.

They report that aging is mostly hereditary, a conclusion that flies in the face of much conventional medical wisdom regarding dieting, exercising and healthy habits. These habits are important for the quality of a person’s life, but they run into another form of conventional wisdom: You can’t make someone into a centenarian, unless that person also has a genetic inheritance of longevity.

“If you are trying to gauge your own chances of getting to 100, I would say look at the longevity in your family,” said Dr. Thomas Perls, a geriatrician and the director of the New England Centenarian Study at Boston University. His study’s published data on U.S. centenarians were used in the new analysis, although he was not associated with the study.

“This paper has a pretty powerful message,” said S. Jay Olshansky, an emeritus professor of epidemiology at the University of Illinois, Chicago, who was not involved in the study. “You don’t have as much control as you think.”

“Some of us are driving a Mercedes and some are driving a Yugo,” he said, referring to the low cost, compact car from the former Yugoslavia.

The study’s conclusions — that genes are powerful drivers of how long people can live — is consistent with what is known about other species, said Daniela Bakula of the University of Copenhagen. Dr. Bakula, a co-author of an outside perspectivepublished by Science alongside Dr. Alon’s paper, added that life spans of every other organism studied, “have a strong genetic component.”

Full article: Genes May Control Your Longevity, However Healthily You Live (NY Times)

#8

Imagine if you said this about intelligence. The thought police would be very upset.

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#9

I think it is generally accepted that things like intelligence and sports ability have an element which is genetic and element which is environmental.

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#10

Yes, though as @Tilmitt says, not something that’s comfortable to acknowledge. Even though every single person on earth has had the experience of coming across people - perhaps daily - who clearly are intellectually constrained and where no amount of environmental intervention is going to change that. But there’s a kind of taboo to bring it down to genes (even in your private thoughts!). And it’s even worse when it comes to kids - not something to ever say or even think, whereas it’s plain as day that kids have different levels of inherent abilities along many vectors. I have many friends with kids, and sometimes it’s heartbreaking. Some couples have tremendous hopes for their kids and go to epic lengths to give their kids every advantage possible, classes, private tutors, special courses and so on, but it’s all a lottery as to the outcome. You can clearly see that the kid is just not capable and no matter the effort, you can’t get blood out of a stone. One couple I’ve known for 30 years had kids whom they tried their best with, but it was clear from like 6-8 of age were hopeless. One kid OD’d at 26, the other is in prison for armed robbery of a liquor store. You have no idea how many resources the parents poured into these kids, when from very early on, it was clearly impossible… the kids were just dumb as rocks. Another example I sometimes think about is a friend who started an extremely successful business - think billionaire status. He is passing on the business to his son, who despite every educational advantage is just a moron. It’s plain to everyone except his dad, that as soon as dad steps away completely, the business will disintegrate, even though there are some very capable managers who if put in charge would do a great job. Instead, the failson will drive it into the ground as soon as dad is gone.

It’s a funny thing from the point of view of social psychology. We may have no problem thinking “he’s an idiot”, but perhaps not “he was born this way”.

I sometimes wonder about this “destiny”, when I see a health fanatic exercising religiously and obsessing about tiny details of their diet - I hope their genes allow for all of that effort to pay off. A friend who was a lifelong vegan (before veganism was even a thing), exerciser and very health aware passed away from pancreatic cancer last year, RIP Charlie, my friend.

Wow, this is turning out to be pretty grim! Let’s get back to the 50-40% we can control, and the latest drug we can put our hopes in.

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#11

There is an issue with mtDNA as well as nucDNA.

#12

It’s worth pointing out that when someone says something like “lifespan is 50% genetic”, I think they mean, “assuming certain background environmental conditions”. Those environmental conditions will shift over time – what we eat, what medicines we take, maybe even what we consider to be “essential nutrients”. In like 100 years if people have access to nanobots to keep their body youthful, they might just consider that part of the background assumptions of modern life – as essential as vitamin C – and wonder what people mean when they say “lifespan is 50% genetic”.

I posted this to both Gemini 3 pro-thinking and GPT-5.2-thinking just to make sure I wasn’t misinterpreting things, and they both agreed:

Bottom line

Your conclusion is right:

  • The paper’s reported “% genetic influence on lifespan” is conditional on the environments represented in the data and on how the authors model what counts as “extrinsic.”
  • With different background conditions (diet, medicine access, public health, accident risk), the measured genetic contribution can indeed be substantially different — and specific genetic risk factors can be made to look much weaker or stronger depending on what interventions are common.

And Gemini 3 pro-thinking:

You are right to conclude that the 50% figure in the paper is not an “intrinsic truth” of human biology, but rather a measurement of how much genes matter given our current (or idealized) environmental conditions. If medical science continues to advance—developing “statins” for every genetic risk factor—we will actually reach a point where the heritability of lifespan decreases again, because we will have successfully mitigated the “bad hands” dealt by the genetic lottery. The paper’s high estimate is essentially a snapshot of how much our genes matter in an era where we have conquered many external threats (like smallpox) but haven’t yet fully “cured” the internal genetic risks.

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#13

So much to say tearing this study down as a narrow rifle shot ignoring all the means one can do to flip epi-genitics!! Then use bioregulators like vilon and or livagen to make those epigenetic changes more permanent. The body and health is alot more plastic then this “directed” research.

Once a population is rendered hopeless; then Alopathica and drugs are more palatable. Such a false flag.

Best to all, keep up the hard work of improving, curt

#14

Yes, kind of depressing but makes sense. Was telling friend I might as well throw out half of my 25+ pills I’m gobbling down every day. Perhaps they’ll help squeeze out another year or so but not going to add 10 years. I’ll keep up exercising since I’ve been doing it since HS and it’s part of my lifestyle. Plus I feel better because of it.

#15

Haha, very well said. I recently attended my kids’ sports day at school and the diversity is just incredible. Some of them run and jump like naturals while others clumsily plod and stamp around and just have hopeless coordination. And these are kids less than 10 years old so you’re not looking at people who’ve had training, coaches etc. Sure, maybe some extra play with their parents would help, but the huge differences must be genetics.

And yeah, logically the same principles would apply to raw intelligence, emotional intelligence, work ethic, or attention span, or the countless other things that will probably determine overall success in a particular metric.

I will say that I think doctors are quite clued up on this. Family history is a huge part of a diagnosis or prognosis, and I think it’s well justified.

However, as you know I’m a big fan of the “low fruit of longevity” idea. While genetics are incredibly important, a lot of people are prematurely shortening their lifespan with actively poor choices that are actionable (smoking, failure to manage hypertension, lipoproteins etc). For example, if my mother and father made it to 70-something, I should be reasonably be hoping that early use of statins, cancer screenings etc should earn me a decent amount of extra time.

They probably would. But maybe genetic influence is a realisation that we actually need to come to as a society. I think some people are born with potential for greatness (by whatever metric you may choose) and others don’t have that capability and never will. While that sounds horrible, if you actually frame things as an inherent property that somebody can’t change, it might actually make society fairer because people are generally becoming more tolerant for intrinsic properties.

For example, most societies are now very accepting of the idea that some things are genetically determined. Many countries are banning homosexual conversion therapy, based on an understanding that sexual attraction has a very large genetic component. It is then determined that trying to change the outcome is wrong, unethical etc and we should accept the person the way that their genes made them.

But it’s an interesting thought experiment to put it another way. Take a below average, slow-learning kid at school. Perhaps trying to push that kid into better grades might be the equivalent of conversion therapy. If it just isn’t within his capability to get an A in maths, then trying to make them work harder, work longer (tutors, extra classes etc) is unfair.

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#16

I recommend reading the book “The Bell Curve”. They make a similar point to you, once you realise that some people will never have the same cognitive ability as others you stop trying to implement policies that will never work and start driving towards policies that will generate better outcomes based on genetic reality. The book was demonised by the censorious post-modern coalition but it actually has a highly compassionate message.

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#17

Absolute taboo amongst the woke.

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#18

Please, lets try to keep the conversation at least somewhat focused on “longevity” :wink:

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#19

:fire: Hot off the press! How heritable is longevity? My take on this Science Magazine study everybody is talking about!

LinkedIn

For the not familiarized, the study shows with new analyses on large twin cohorts, a pretty simple yet under-appreciated idea: when accounting for accidents, infectious disease, homicides, etc. (extrinsic mortality), heritability of human lifespan is not 7% or 20% as shown in previous studies, but over 50%!

I highly appreciate Uri and team work here, since this opens a whole new paradigm in the genetics of human longevity. This will certainly stimulate many to try and pinpoint which variants (likely thousands) are responsible for achieving 100 years.

Fei Wu in my group has demonstrated that immune system genes (those in control to fight infection – THE strongest pressure for survival during evolution), largely overlap with aging genes in tissues (see table attached).

And to add flavor, in 2015 in a Cell paper with Petter Brodin and Mark Davis, we showed that >80% of biological variation in the immune system is non-heritable.

Trying to make sense of these layers.

Uri’s team may have overseen a few pieces:

  1. Heritability may also reflect gene-environment correlation
    Families share DNA but also diet, socioeconomic status, exposures, behaviors, etc.
    Twin designs correct for a lot, but not everything.
    Modern exposome science suggests this is way bigger than once thought.
    :point_right: How about this? A fraction of “gene heritability” may be “heritability of environments” :facepunch:

  2. Antagonistic pleiotropy is almost certainly in play!
    Variants that improve early survival often harm late-life health. Here, classic immune examples: strong inflammatory responders survive infection but develop cardiometabolic disease (#1 cause of death) later in life.

:brain: I think a 50% heritable component is largely compatible with pleiotropy, it almost predicts it!

  1. The paper focuses on mortality and not biological aging rate. This is really important. Mortality is influenced by acute disease, healthcare access, randomness (stochasticity), trauma, treatment response, etc.

But two people can age biologically at very different speeds yet die at similar ages.

:point_right: What Uri’s Science paper may NOT fully capture is the heterogeneity in aging trajectories (which we can accurately and precisely measure with regular labs Cosmica Biosciences).

In summary, important aspects to consider (not addressed in the paper, in my view):
:white_check_mark: gene–environment correlation
:white_check_mark: immune mediation
:white_check_mark: trajectory vs mortality endpoint

While lifespan is somewhat heritable, the mechanisms of how heritability expresses are dynamic and largely dependent on immune set points and inflammatory processes (Furman, Nat Med 2019)

OK, last, it also makes me think of the idea I had during COVID-19 of a mRNA vaccine for aging that my friend Ronjon Nag at AGEMICA is now working on -are there genes hubs here we can target)?

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