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Medicine Science

Scientists Are Working To Eliminate Senescent Cells (theguardian.com) 151

An anonymous reader quotes a report from The Guardian: In a lab just south of San Francisco I am looking at two blown-up images of microscope slides on a computer screen, side by side. The slides are the same cross-sections of mouse knees from a six-month-old and an 18-month-old animal. The older mouse's image has a splattering of little yellow dots, the younger barely any. That staining indicates the presence of so-called senescent cells -- "zombie cells" that are damaged and that, as a defense against cancer, have ceased to divide but are also resistant to dying. They are known to accumulate with age, as the immune system can no longer clear them, and as a result of exposure to cell-damaging agents such as radiation and chemotherapy. And they have been identified as a cause of aging in mice, at least partially responsible for most age-related diseases. Seeing the slides, it makes me worried about my own knees. "Tell us about it," says Pedro Beltran who heads the biology department at Unity Biotechnology, a 90 person-strong company trying to halt, slow or reverse age-associated diseases in humans by killing senescent cells.

Developing therapies to kill senescent cells is a burgeoning part of the wider quest to defeat aging and keep people healthier longer. Unity, which was founded in 2011, has received more than $385m in funding to date including investment from big tech names such as Amazon's Jeff Bezos and PayPal co-founder Peter Thiel. It went public this May and is valued at more than $700m. Its first drug entered early clinical trials in June, aimed at treating osteoarthritis. Other startups with zombie cells in their sights include Seattle-based Oisin Biotechnologies which was founded in 2016 and has raised around $4m; Senolytic Therapeutics whose scientific development is based in Spain and which was established last September (it won't disclose its financing other than to say it has a first round, which will allow it to reach clinical trials); and Cleara Biotech, formed this June backed by $3m in funding and based in the Netherlands. In addition, Scottish company CellAge, also founded in 2016, has raised about $100,000 to date, partly through a crowdfunding campaign.
The report goes on to detail Unity's plan to kill senescent cells. Their method is to target the biological pathways senescent cells use to resist the normal death of aging cells. "The company's approach is to find small molecules (so called 'senolytics') that can do this," reports The Guardian. "But because small molecules, by their nature, can get everywhere in the body, the approach is prone to unwanted side-effects." As a result, the company has turned to localized treatment.

Meanwhile, Oisin is trying to kill all a person's zombie cells in one go. "The idea is to load the body with nanoparticles that insert a 'suicide gene' into every cell," reports The Guardian. "It only triggers if a cell has a lot of particular protein (p16) that acts as a marker of zombie cells, albeit imperfectly." It plans to test this method on late-stage cancer patients next year.
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Scientists Are Working To Eliminate Senescent Cells

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  • People need to die (Score:5, Insightful)

    by MikeDataLink ( 536925 ) on Sunday October 07, 2018 @03:28PM (#57442124) Homepage Journal

    It's the only way for change to happen. Imagine in people from 200 years ago were still alive and voting. We'd never progress as a society.

    "And that is as it should be, because death is very likely the single best invention of life. It is life's change agent. It clears out the old to make way for the new."

    • To paraphrase Max Planck: "Progress is made one funeral at a time."
    • by Anonymous Coward

      Strong argument: donât try saving anyone as we canât have old men and women voting ðY'

    • by Wycliffe ( 116160 ) on Sunday October 07, 2018 @04:00PM (#57442226) Homepage

      It's the only way for change to happen. Imagine in people from 200 years ago were still alive and voting. We'd never progress as a society.

      "And that is as it should be, because death is very likely the single best invention of life. It is life's change agent. It clears out the old to make way for the new."

      If we could completely stop aging, the average life expectance would only jump to about 300. You can calculate this by extrapolating out the death rate of a 25 year old. People would eventually die from other things besides old age. This would likely be a net benefit to society. We would greatly reduce our heathcare costs and people wouldn't have to retire because they are no longer capable of working. It would likely have other effects too. People might decide to be more careful with their driving and eating habits if they knew that it was up to them how long they could live.

      • by AsmCoder8088 ( 745645 ) on Sunday October 07, 2018 @04:52PM (#57442406)
        I was going to bring this up as well. Also, imagine the usefulness of a healthy 300 year old. They would have not only a unique perspective and wisdom about things but also the energy to put it to good use.
        • by mrbester ( 200927 ) on Sunday October 07, 2018 @05:14PM (#57442462) Homepage

          They'll probably be maintaining COBOL and FORTRAN systems.

        • And the first person to undergo this life extension will be...Hitler.

          • by Anonymous Coward

            Hitler didn't die of old age.

      • Re: (Score:2, Insightful)

        by Courageous ( 228506 )

        Accidental death, suicide, and homicide kill 36,726 annually. In that age group, roughly 43M are alive. That 1:1171 or so chance of dying from those causes by my calculation.

        • Accidental death, suicide, and homicide kill 36,726 annually. In that age group, roughly 43M are alive. That 1:1171 or so chance of dying from those causes by my calculation.

          But that doesn't mean that you live to 1171, it means that on average everyone is dead by approximately age 1171. Based on those numbers, 50% should still be dead by about age 500 and chances are that the first life extensions will likely not be perfect and there will be other gotchas that would still get you long before that (like heart attacks)

        • Accidental death, suicide, and homicide kill 36,726 annually. In that age group, roughly 43M are alive. That 1:1171 or so chance of dying from those causes by my calculation.

          The important point isn't whether it's 300 or 1000 years, it's that it's vastly limited. Some will make it to 20,000 (roughly Gandalf's "300 lifetimes") by luck and timid living.

          Unlike age 70, say, the average here doesn't fall off a rock. This is more like a half life average, so if it is 300 years, half will be dead, but 1/4 will still be alive in 600 years, and 1/8 in 900 years, and 1/16 in 1200 years.

          Not likely anyone would live to 21,000 (1 in 2^^70) but if 1000 is half life, many thousands would.

          Any

          • "Half life" thought of like radioactivity is not now, and probably never will be, a valid way of thinking about animals. Animals, in the absence of disease, predation, starvation, etc. tend to mostly live to more than half of a maximum life span, after which the death rate increases greatly until everyone is dead at the maximum life span. Experiments that increase a species' maximum life span (there are a few such experiments) still show the same sort of survival versus time curve, even if the point at whic
      • by Gr8Apes ( 679165 )

        The last study I saw on this made the assumptions that the life age of the body would be set between 23 and 28. Based on the activities people do at that life age, the average expected lifespan was 220 IIRC. That was based on people having the energy and lifestyles that would make them more active and more likely to engage in activities and stupidities that would end in disaster, just to keep the interest in living higher.

        On the top side, something like 1% of the population would make it to 1000, so the ol

        • I would say the death rate of a 40 year old would be a better number to use. You have mostly stopped doing stupid crap, you're mostly done with children, but you also are starting to see health related stuff like smoking, heart disease, diabetes, etc... Stopping aging likely wouldn't make all the wear/tear on the body stuff magically disappear. It would take additional breakthrus to be able to reverse all the wear/tear issues. Heart disease is already the number one killer and would likely remain so ev

          • by Gr8Apes ( 679165 )
            The study actually assumed being able to control all age related wear and tear diseases. To answer the AC, it also assumes implicitly that 2 factors increase the risk taking behavior, that boredom coupled with youthful energy drives activity and that the mix of youthful hormones and enzymes affect brain activity. IOW, you don't ever see 40, you'll think, feel, and act like a mid-20s person.
          • Although heart disease may remain the number one killer, much heart disease can be either prevented or delayed. Except for heart defects present at birth (like malformed valves), most heart problems stem from bad nutrition and inadequate exercise. Fixing the "primary causes of aging" also prevents or delays most heart disease.
    • by dissy ( 172727 )

      No one is talking about removing the ability to die.
      We're talking about removing the ability for old age to kill us.

      A bullet to the head, as well as thousands of other ways to be killed, not only remains but then becomes even more of a thing to avoid when it will cost you hundreds of years of your life ahead instead of just a small handful.

      Then clearing out the old to make way for the new becomes a choice regarding how.
      Either you move aside and live out the rest of your long and healthy life, or refuse and

    • Re: (Score:2, Insightful)

      by Anonymous Coward

      It's the only way for change to happen. Imagine in people from 200 years ago were still alive and voting. We'd never progress as a society.

      "And that is as it should be, because death is very likely the single best invention of life. It is life's change agent. It clears out the old to make way for the new."

      This is cute non-sense that you feel is funny to engage in because you don't think extending life is actually a possibility that relates to your life. Once you have cancer or Alzheimers or even just your brain, muscles and bones atrophy with age, and there is a fix available, you will not reject it on the basis that your old-fashioned thinking should not be around any more. In no other context would you be anything but horrified at a suggestion to kill off large population groups because their thinking is n

      • Your overly-trite response based on discussing the effects on an individual. The OP's discussing the effects on society as a whole.

        People do change their minds and the longer-term perspective and accumulated competence of people living for, say, 200 years will do a lot of good

        Well, I'm looking at the Boomer generation and what they are insisting society must do. Currently it features whining about very slight harm done to powerful rapists, obsession over who is sitting in the next stall in the bathroom, rich people must be given more money, housing supply must be massively limited to increase their own wealth, and insisting they should get to destr

    • by Anonymous Coward

      You're missing the point. People progress because they adapt to a changing world. As you age you literally lose the mental plasticity required to asymilate new information and change your behavior. Slowing down or preventing these negative age-related changes wouldn't leave us with an intreched class of 'stubborn old people', quite the opposite.

    • Re: (Score:3, Insightful)

      by ChrisMaple ( 607946 )

      People need to die. It's the only way for change to happen. Imagine in people from 200 years ago were still alive and voting. We'd never progress as a society.

      What a vile and disgusting statement, false in every regard. What makes you think that people don't get wiser as they get older? What makes you think change in society, which you call progress, will be an improvement? Judging from the proclamations of those young people making the most noise in politics today, progress is torturing all males to death

      • What makes you think that people don't get wiser as they get older?

        People.

        Judging from the proclamations of those young people making the most noise in politics today, progress is torturing all males to death and giving 3-year-olds the vote.

        Out of interest, are you old?

      • by AmiMoJo ( 196126 )

        What makes you think that people don't get wiser as they get older?

        "Wiser" is too vague to be a useful metric. We should look at the way they tend to vote, since that was the issue cited as holding back progress.

        While not all older people are conservative, there is a clear trend towards conservatism as people age. It's not clear to me that the trend is because they are "wiser". For example, at the time same-sex marriage become legal in many countries there was still a majority of over 65s opposed to it. If their numbers had swelled due to people living to 200 then it might

      • by strikethree ( 811449 ) on Monday October 08, 2018 @09:28AM (#57444978) Journal

        What a vile and disgusting statement, false in every regard.

        Well, that is one way to look at it.

        What makes you think change in society, which you call progress, will be an improvement?

        There is no way to tell ahead of time whether or not there will be an "improvement"; however, like Evolution itself, over enough time, things seem to "advance".

        As a person who is subject to dying and not terribly far away from it, I support the idea of natural death. It causes change. There are some Golden Ages which ended because of death and that seems to be a shame; however, the majority of time, it has been self serving kings and emperors who have made everyone's lives miserable and it is good that things changed.

        I think there is a quote by Max Planck (not going to verify because it really doesn't matter WHO said it) that goes something like this: The progress of Science advances one death at a time. Once a scientist has found a "truth", they tend to enforce that truth far beyond the applicability of that truth. Could you imagine still "believing" in the Niels Bohr model of the atom?

        And yet another strangely prophetic captcha: stings

        • by urusan ( 1755332 )

          I'm pretty sure Niels Bohr didn't believe in the Niels Bohr model of the atom late in his life.

        • by Tablizer ( 95088 )

          ...natural death. It causes change. [for example] self serving kings and emperors who have made everyone's lives miserable and it is good that things changed.

          So if bots become sentient, should we terminate them after X years to avoid getting stuck in a rut?

          Similarly, should we toss Linux after X years and start over with a new OS?

          You might say, "but we can change and improve those things". If that's the case, then would you change your mind about human death if we could improve individual humans?

      • What a vile and disgusting statement, false in every regard. What makes you think that people don't get wiser as they get older?

        The entirety of history.

        What makes you think change in society, which you call progress, will be an improvement?

        Almost the entirety of history. It's around 70/30.

        Judging from the proclamations of those young people making the most noise in politics today, progress is torturing all males to death and giving 3-year-olds the vote.

        Is this massive pile of stupid you are vomiting forth supposed to be "wisdom"?

        • Have you listen to the news recently, where one shrill "feminist" declared that men should be killed, castrated, and their genitals fed to pigs?
    • by fermion ( 181285 )
      Just imagine if the slavers were still in control of the US...

      But my real concern is that we don't really know what the side effects of this are. We keep trying to medicate all the 'negative' aspects of our lives, and it keeps biting us in the ass. We want everyone to be happy, and have a 'normal' psychological profile, and what we get it an opioid epidemic that is killing people. We are relative certain the appendix is vestigial, and removing it is of no great significance, but the preponderance of ca

      • by c6gunner ( 950153 ) on Sunday October 07, 2018 @06:46PM (#57442742) Homepage

        Who know what the side effects of eliminating these cells are going to be.

        Long life.

        They may not appear for generations. We thought that aggressive use of antibiotics and routine use of antibacterials would be a good idea

        They are. We live longer, healthier lives than ever in human history. All thanks to those good ideas.

        until we bred the superbugs that one day could eliminate us.

        We didn't breed "superbugs". Life evolved, as it always does. The phrase "superbug" is fearmongering nonsense meant to attract attiontion. Every disease which we couldn't fight in the past was a "superbug". Measles. Polio. Smallpox. The plague. They killed and maimed incredible numbers of people and we had no defense against them. Today Ebola is one of the most potentially harmful diseases on the planet, and it has absolutely nothing to do with antibiotics or antibacterials.

          I've never understood the mindset of the horribly confused people who seem to believe that we shouldn't bother fighting diseases or pests because new ones will evolve. That's like suggesting that we shouldn't eat today because we'll just be hungry again tomorrow.

      • Who know what the side effects of eliminating these cells are going to be.

        Well, just from the summary I'd say if you eat the wrong foods, all the rest of the cells in your body might self-destruct.

      • We keep trying to medicate all the 'negative' aspects of our lives, and it keeps biting us in the ass

        [Citation Required]. Specifically that the "biting us in the ass" part happens more often than positive results.

        We want everyone to be happy, and have a 'normal' psychological profile, and what we get it an opioid epidemic that is killing people

        [Citation Required]. Specifically, that the people dying of drug overdoses received psychological treatment or other evidence that they were not "normal".

        What happens is we make people have incredibly shitty lives with no future so that a very small number of people get extremely rich. The "normal" response to that is despair and escapism, which frequently manifests itself as drug use.

        We are relative certain the appendix is vestigial, and removing it is of no great significance, but the preponderance of caution that defines medicine says that maybe we should treat appendicitis as it could be a repository for important bacteria.

        .....are

    • by Tapewolf ( 1639955 ) on Sunday October 07, 2018 @06:21PM (#57442642)

      It's the only way for change to happen. Imagine in people from 200 years ago were still alive and voting. We'd never progress as a society.

      "And that is as it should be, because death is very likely the single best invention of life. It is life's change agent. It clears out the old to make way for the new."

      It also causes valuable lessons to be lost.The people who experienced Hiroshima and it's after-effects are better placed to fight against it happening again than people who just read about it as bored schoolchildren. It becomes easier to deny the holocaust when the survivors are dead of old age. And regulations put in place after the Great Depression were swept away by later generations who considered them obsolete relics, until the consequences became apparent in 2008.

    • Re: (Score:1, Insightful)

      by roman_mir ( 125474 )

      It is always safe to assume that socialists, communists, fascists and other types of collectivists hate individuals as they espouse their love to humanity as a whole.

      AFAIC individuals matter while the collective does not. I am all for infinite life and completely against aging and dying from so called 'natural causes'. However anybody is and should be free to terminate their own existence if they so choose. It would be interesting to see how many collectivists would off themselves for the sake of their v

    • Because nobody ever gained experience and wisdom as they age.

    • If you would do us the kindness to RTFA, you would realize that your lifespan will not be increased if you were suddenly able to eliminate all of your senescent cells. Life extension is not on the table with this approach, as it is with techniques that mimic caloric restriction.

      However, should your senescent cells all undergo sudden removal, you would find yourself free from a number of age-related diseases. The article asserts that even a small number of senescent cells are able to act as powerful pathogen

      • If you'd actually Read The Fucking Article you'd know that

        Most of the benefit seen in mice seems to be in extending healthspan, the time free of frailty or disease, and as a result median lifespan (being sick, after all, is risky)

        I guess you missed that part? Or were you confused by:

        True longevity – the maximum time the animals remain alive for – remains relatively unchanged, though studies published in July and September 2018 show an extension of remaining lifespan in mice that were treated when they were very old.

        So, the very longest-lived individuals might not benefit much from this, but many more of the population might be able to reach that age.

        Lifespan of individuals increased, maximum longevity maybe not. Or they might just need more treatments. The future will tell us.

    • OK, I'd rather take the risk of not dying, thanks. Your idea is an intuition, not based in fact. It is easily countered by the fact that if our most skillful people didn't keep dying, progress would happen much quicker.
      • I haven't died yet, and I don't intend to start. I wouldn't jump off a bridge just because lots of other people had done it.

    • It's the only way for change to happen.

      They have things called education and learning. And you don't have to go back 200 years. "Gay marriage" was socially unacceptable (by more than half the populous), only 10 year ago, in the USA [google.com]. And forget about it in the middle east.

      If you think old people are inherently backwards and shouldn't vote, then you're RAGINGLY ageist.

      Consider how many resources it takes to raise a surgeon from birth through all that schooling, to actually performing surgery by (on average) age 36.8. And then they retire by 65. H

    • Worse: why waste any time on this when climate change is being ignored, and we're well on the way to a slow extinction-level event for us anyway? Unless hearts and minds of 7,000,000,000 people are all changed more or less simultaneously, nothing is going to save us.
    • It's the only way for change to happen. Imagine in people from 200 years ago were still alive and voting. We'd never progress as a society.

      "And that is as it should be, because death is very likely the single best invention of life. It is life's change agent. It clears out the old to make way for the new."

      First of all we'd be up to 50 billion by now.

      Secondly, people voting is not a problem. That's amenable to persuasion (as long as you aren't a dick about it, which is, sadly, what most preaching to the choir politics is, e.g. the entire Kavanaugh thing most recently). People need to discover a better way on their own so they don't feel attacked and get defensive.

      Anyway, the real problem is dictatorship. With the greatest psychopathic charismatics in history (the ability to lie convincingly is key) running

    • by urusan ( 1755332 )

      If you want some solid evidence that you don't need to clear out the past generations to progress a cause, consider how fast recent social shifts have occurred. From 2004-2017, opposition to gay marriage in the US went from 60% to 32% (http://www.pewforum.org/fact-sheet/changing-attitudes-on-gay-marriage/). The US didn't lose 28% of its population in 13 years, it lost around 10.9% of its population in that time frame (calculated from this https://tradingeconomics.com/u... [tradingeconomics.com]). Even assuming that every old pers

  • by fahrbot-bot ( 874524 ) on Sunday October 07, 2018 @03:29PM (#57442132)

    "zombie cells" ... have ceased to divide but are also resistant to dying.

    Init will take care of them eventually.

  • by Empiric ( 675968 ) on Sunday October 07, 2018 @03:30PM (#57442140)
    Spoiler alert: You die anyway.
    • Nihilistic angst is paralyzing. The rest of us will live the best lives possible.

      • by Empiric ( 675968 )

        No, I just went ahead and solved the issue with an approach that works.

        Don't assume your context is everyone's. That's epistemologically invalid.

        • What issue did you solve, exactly? As far as I can tell you just walked in, shit on the very suggestion of a solution, then declared yourself triumphant. Please explain to me how your approach "works" as anything other than a trolling tactic?

        • Nothing, really? You've got nothing to respond with aside from the deafening silence? Sock puppet mod points do not an argument make. So far you've failed to convince me you have a coherent thought process.

    • by SuricouRaven ( 1897204 ) on Sunday October 07, 2018 @03:51PM (#57442202)

      Medicine is a history of doctors and scientists facing up to Death, raising their middle finger towards the reaper and declaring, "Not today!"

  • How do we know senescent cells don't play some other important role?

    So many times we think something is 'bad', when it's actually quite helpful (and a reason it evolved to that point). Let's sterilize everything - oh wait, now our immune function is compromised and pathogens get stronger. Lactic acid is why muscles hurt and stop - oh wait, it's actually fuel for muscles and transports out the actual 'bad stuff'.

    Maybe they're genuinely bad, useless cells...but it seems more often than not this is the wrong w

    • There's some speculation that the process of intermittent fasting -- from half a day to 8 days or more, simulating conditions that occurred in nature -- allows the body to clear out some senescent cells through autophagy. If true it would show that there is value in removing them, though non-drug induced process would probably be preferable for an average person.

    • More often than not? Want to back that up? A few examples that stand out are not enough for you to think this.

      • I could return to you with the same question: where's the evidence that there will be zero negative side effects from the removal of senescent cells?

        Or: how many examples would satisfy you?

        Geez bub, this is a discussion site, what's the harm in a little speculative discussion?

    • It could be that the body simply leaves them around in times of plenty, just waiting for the inevitable winter time when we would run out of food, and then break down the senescent cells to scavenge them for proteins. Our body doesn't have a dedicated protein store, like it does for fat and carbs. There is a lot of protein stored in the muscle, but breaking down muscle in times of hardship will be detrimental to your abilities to find the scarce food. Having some extra junker cells around could be an evolv

      • Interesting idea.. On this thread though, are enough of these cells in a typical person to really make a difference on protein requirements? I'd imagine muscle tissue would be a considerably larger source. I doubt we have muscle-sized amount of senescent cells, eh?

        • It's not just whole cells that can be scavenged, but also old organelles within each cell. You only need around 50 grams of protein on a normal day. During times of famine, construction of new cells is slowed down to minimal maintenance, so protein requirements are lower. There's about 10 kg of total protein in a human body, so even if just 1% (wild ass guess) of that is kept in the form of senescent cells and organelles, it should provide enough material to last a couple of extra days without impacting phy

          • Oh, for sure, we're fine for a long time without consuming protein...but it wouldn't be a straight conversion of 50g of senescent cells to 50g of usable protein. I don't know the breakdown, but I'd imagine that most of the cell isn't protein...and the other side of the question is how many g of senescent cells are in the average person?

    • How do we know senescent cells don't play some other important role?

      Clinical trials.

      You know, like how all medicine gets made these days.

      Duh.

  • It's interesting that the comments have skewed toward a fear, an existential fear, of this research. MIT Tech Review (https://www.technologyreview.com/s/612124/clearing-out-old-cells-might-help-the-brain/) on 9/19/2018 first caught my eye. The goal seems less about extending one's lifespan as retaining 'vigor' as we age. The diseases, age-related impairments, that are within the scope of this research are considerable. I haven't seen any documentation about the possible benefit of longer life. Doesn't sound

  • Nature already figured this out. Autophagy kicks in in a fasted state.
  • I think the only thing that isn't dying is this story; I've read an article talking about how Death itself will be cured "any day now" for the past 20 years, and we are still nowhere near closer to a cure than when Indiana Jones set out looking for the Holy Grail.
    We can't even cure Male Pattern Baldness, where the cure has been 5 years away for 50 years.

    One other thing, if a cure does come out I'll be glad to take it; if only to find out what discoveries they make out in the Universe. It is strange to see t

  • How ironic if we were to eliminate ageing just as the planet decides to rid itself of us irritating little ticks.
    • How ironic if we were to eliminate ageing just as the planet decides to rid itself of us irritating little ticks.

      People who can actually live long enough to experience a real change of climate might be more inclined to pay attention to the possibility of a poor change.

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