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Medicine Science

Molecule Kills Elderly Cells, Reduces Signs of Aging In Mice (sciencemag.org) 128

An anonymous reader shares an excerpt from a Science Magazine report: Even if you aren't elderly, your body is home to agents of senility -- frail and damaged cells that age us and promote disease. Now, researchers have developed a molecule that selectively destroys these so-called senescent cells. The compound makes old mice act and appear more youthful, providing hope that it may do the same for us. As we get older, senescent cells build up in our tissues, where researchers think they contribute to illnesses such as heart disease, arthritis, and diabetes. In the past, scientists have genetically modified mice to dispatch their senescent cells, allowing the rodents to live longer and reducing plaque buildup in their arteries. Such genetic alterations aren't practical for people, but researchers have reported at least seven compounds, known as senolytics, that kill senescent cells. A clinical trial is testing two of the drugs in patients with kidney disease, and other trials are in the works. However, current senolytic compounds, many of which are cancer drugs, come with downsides. They can kill healthy cells or trigger side effects such as a drop in the number of platelets, the cellular chunks that help our blood clot. Cell biologist Peter de Keizer of Erasmus University Medical Center in Rotterdam, the Netherlands, and colleagues were investigating how senescent cells stay alive when they uncovered a different strategy for attacking them. Senescent cells carry the type of DNA damage that should spur a protective protein, called p53, to put them down. Instead, the researchers found that a different protein, FOXO4, latches onto p53 and prevents it from doing its duty. To counteract this effect, De Keizer and colleagues designed a molecule, known as a peptide, that carries a shortened version of the segment of FOXO4 that attaches to p53. In a petri dish, this peptide prevented FOXO4 and p53 from hooking up, prompting senescent cells to commit suicide. But it spared healthy cells. The researchers then injected the molecule into mutant mice that age rapidly. These rodents live about half as long as normal mice, and when they are only a few months old, their fur starts to fall out, their kidneys begin to falter, and they become sluggish. However, the peptide boosted the density of their fur, reversed the kidney damage, and increased the amount of time they could scurry in a running wheel, the scientists report online today in Cell. When the researchers tested the molecule in normal, elderly mice, they saw a similar picture: In addition to helping their kidneys and fur, the molecule also increased their willingness to explore their surroundings.
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Molecule Kills Elderly Cells, Reduces Signs of Aging In Mice

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  • by Opportunist ( 166417 ) on Friday March 24, 2017 @06:05AM (#54101159)

    More hair and better kidney function?

    In other words, it's like washing down Rogaine with beer?

  • by SCVonSteroids ( 2816091 ) on Friday March 24, 2017 @06:15AM (#54101197)
    We're finding all these awesome ways to extend and enrich their lives. God I wish I was a rat...
  • Sounds nice! (Score:5, Interesting)

    by Kokuyo ( 549451 ) on Friday March 24, 2017 @06:19AM (#54101203) Journal

    I'm glad we seem to be on track to tackling frailty with age... however, we're nowhere when it comes to tackling our resource problems...

    A cynical though: Will we stay healthy and strong longer just so we can send the 50 year olds to war over water instead of just the 20 to 30 year olds?

    • by Lennie ( 16154 )

      Sounds about right, unless we can reduce the price of electricity, as some think we can. Imagine how that would help societies:

      https://www.youtube.com/watch?... [youtube.com]

    • The Acheron Group came up with the gerontological treatment, making it possible to live 200 years.

      On Earth it led to social friction and a Malthusian crisis.

    • Re: (Score:3, Insightful)

      by Anonymous Coward

      If we would live longer we would stay productive much longer in life, so it could possibly be a benefit too. Just because someone lives longer may not cause the population to grow since it may cause people to wait longer before having children..

      Imagine what could happen if researchers had 20-30 years extra, instead of 40 years in total, of productive lives and allowing them to continue using their experience and push their research even further. Just look at the guy that invented the current lithium-ion bat

      • You are assuming that anti-agapics will only prolong the productive years. What if they prolong the long, decaying years as well? I mean it's already obvious that, at least within the US, people are in no hurry to let themselves die just because they're old and worn down, and an anti-agapic might well work to extend those non-productive years just as log as the productive ones.

        There's a whole lot of knock-on effects to consider.

        • The older segments of society generally are the major customers of most tourism industries in their "non-productive" years, so invest your money in those industries if people start living longer.

        • You are assuming that anti-agapics will only prolong the productive years. What if they prolong the long, decaying years as well?

          What if it only prolongs the life of rich people? 'Cause I'm pretty sure anything developed won't be made available to the unwashed masses - or even the washed ones. (Don't know which are here on /.)

        • What if they prolong the long, decaying years as well?

          I'd assume, in that case, that most people would stop taking the antiagathics at some point.

          I mean, 120 years of prime adulthood with antiagathics? Great! Followed by either 30 years of old age sans antiagathics or 120 years of old age with them? Put the antiagathic bottle down, and go out relatively quickly.

          • I'm far less certain of that - look how many people take life-extending drugs now, so that their failing heart/liver/kidneys/whatever won't kill them "before their time"

            What makes you think a drug that benefits basically every aspect of your health, plus makes you look and feel younger, would be any less appealing? Granted, after a few decades of failing health perhaps the allure of several more would wear thin. Then again, our culture is rather obsessed with putting off dying as long as possible, at almo

      • Anything to combat aging.. just look at the amount of resources we use to take care of the sick and elderly. And as a big bonus everyone would have much better life-quality with less sickness etc.

        You assumed that the resources we use to take care of sick/elderly will become available if we can live longer with healthier life? What do you think we need to pay to get the healthier life? Nothing is free. They just replace drugs that prolong (not cure) your life with this drug that slows down your aging... No, you won't have extra money to spend regardless...

    • I'm glad we seem to be on track to tackling frailty with age... however, we're nowhere when it comes to tackling our resource problems...

      A cynical though: Will we stay healthy and strong longer just so we can send the 50 year olds to war over water instead of just the 20 to 30 year olds?

      No sir. Even if we can stop them from physically aging, their brains reach a point where they're not malleable enough to blindly follow orders.

    • I'm glad we seem to be on track to tackling frailty with age... however, we're nowhere when it comes to tackling our resource problems...

      A cynical though: Will we stay healthy and strong longer just so we can send the 50 year olds to war over water instead of just the 20 to 30 year olds?

      Sounds really as a micemare.

    • Re:Sounds nice! (Score:5, Insightful)

      by bluefoxlucid ( 723572 ) on Friday March 24, 2017 @09:00AM (#54101683) Journal

      Resource problems are a myth, in a sense. Population always expands until scarcity: at a point, you can't scale production of some products without investing more labor, which means the basic cost of those products increases, the economization of means decreases, the poor get poorer, and more people become poor. At that point, population expansion slows until technical progress raises the scarcity cap.

      Take food. Without GMO, fertilizers, pesticides, irrigation, tractors, and other modern intensive techniques, you need more land to grow the same food. That doesn't just mean more labor per yield of food; it also means you run out of good-climate, good-soil, accessible-irrigation land with a lower total food-per-year yield. Bump that and you can have more population.

      The resource scarcity issue is constant, and has always been constant. When we find more, we expand.

      • by Nemyst ( 1383049 )
        I'm not sure the argument flies with actual humans. Remember, we're not rational agents.

        Just look at many African countries, where everything is in constant shortage. They shouldn't be having kids, right? And yet they have way more than highly industrialized, rich countries. A lot of them will die, but more will survive with just the bare minimums, exacerbating the already evident shortages. Sure, eventually the population would reach a tipping point, but that would play out as more children dying than su
        • Look at the United States, the United Kingdom, China, France, and Germany. Sure, there seems to be tons of food, employment, etc... except if you're in the bottom 5% of the country, since we have about 5% unemployment and about half of those are begging on the streets and getting their food from trash cans.

          In African nations, they have a lower quality-of-life and a reduced standard-of-living. They outbreed the failures of their healthcare systems--we do, too, but we have great healthcare and so don't ha

        • I'm not sure the argument flies with actual humans. Remember, we're not rational agents.

          Just look at many African countries, where everything is in constant shortage. They shouldn't be having kids, right? And yet they have way more than highly industrialized, rich countries. A lot of them will die, but more will survive with just the bare minimums, exacerbating the already evident shortages. Sure, eventually the population would reach a tipping point, but that would play out as more children dying than surviving, causing the population to stabilize. That's utterly inhumane and not something you can rely on for population control.

          Well, they are actually rational, but their way of thought could be different from yours. You should never attempt to compare the view from the 1st and 3rd world countries. They are 2 different cultures and often times a comparison won't work.

          The way they think is that they need kids because they hope/expect that their kids will grow old enough to help them work. Eventually, when the parents get older, their kids will take care of them. Then they need to have as many as they can because, as you said, some o

        • I'm not sure the argument flies with actual humans.

          Just look at the data [wikipedia.org].

          The main reason behind the dramatic decline in children per woman, even in developed countries, is probably the similarly dramatic improvement [worldbank.org] in infant and childhood mortality seen over the last several decades (and not scarcity as suggested above).

          Even in developing countries, people prefer quality to quantity when it comes to children. If they're confident their children will survive to early adulthood, they have fewer children.

      • Your entire statement proves your are wrong or outright evil. You claim resource problems are a myth then say that scarce resources cause poverty and that means population expansion ceases. First of all poverty IS a resource problem. Poverty = not enough money = not enough resources.

        Population expansion is caused by more births than deaths. Poverty does not reduce the birth rate, it increases it. But it does increase the death rate more than the birth rate.

        Population up with scarce resources = po

        • Okay, well, with a cut-down population, you also lose the labor required to produce to support the population. Then labor becomes a short resource. Without a labor reserve, you can't take advantage of technical progress, and so the economy becomes unstable and poverty becomes more wide-spread, rather than the normal model of developing better access to food, clean water, and healthcare as technology improves.

          It is true that population does expand to fit our current resources, but it is not true that = constant scarcity.

          Population expands to fit our current resources because it hits a wall. Communist leaders have

          • Okay, well, with a cut-down population, you also lose the labor required to produce to support the population. Then labor becomes a short resource. Without a labor reserve, you can't take advantage of technical progress, and so the economy becomes unstable and poverty becomes more wide-spread, rather than the normal model of developing better access to food, clean water, and healthcare as technology improves.

            This flies in the face of history. Cut-down populations lead to boom times of reduced poverty and inequality (most notably after the black plague). A terrible way to get a boom time, but that's what happens.

            • Historically, cut-down populations lead to growth. Nobody in history established a policy to reduce the population "to conserve resources", and then held it down that way. The GP is suggesting that population is too big; there is a popular argument that we need to cut the world population back a few billion to conserve our resources, and he's made the first part without stating the conclusion. My response was in that context: the economic boom you describe wouldn't happen because we would prevent growt

      • The resource scarcity issue is constant, and has always been constant. When we find more, we expand.

        Just like closet space.

        • 978sqft houses in 1950. 2,300sqft in 2003. We buy more shit, we get bigger houses, we fill the houses with more shit.

    • We've certainly got the resources, at least in the developed world. There are a lot of questions as to what the implications would be, though, such as whether this would extend fertile years or not. If we're talking about living to, let's say 200, does that mean double the years in each traditional age category, or simply another 100 years at (adult/middle aged/60s)? Population growth is negative in pretty much the entire developed world, so this might have a positive impact on countries that are at the lea
    • Most developed nations are undergoing a shrinking demographic. People having less children and living longer is more efficient and environmentally friendly than the opposite.
    • by Megol ( 3135005 )

      There are no resource problems. It's a myth. It's the same as people complaining about increasing population in the US will soon lead to space problems - when the US is sparsely populated and have extreme amounts of resources not being used today.

      Often (don't know if it applies to you) this is actually a complaint that the current society model will not continue unmodified in the future. That is true - already there are problems in certain hotspots where water and energy are consumed or rather wasted in ext

    • Resource problems?

      What ???

      I only know one guy who died of starvation (been middle class all my life), and it wasn't because he ran out of food.

      You go to these 3rd world / emerging countries where corrupt governments stop new businesses and vampire away all the funds they earn and explain how that is a resource problem. Think of the Venezuela horrors where grocery stores are only open for a few hours a day because of government imposed artificial scarcity. And now I suppose you're suggesting a gover
    • Shit, we already went to war over Iraqi oil.

  • by Chrisq ( 894406 ) on Friday March 24, 2017 @08:39AM (#54101591)
    If this allows you to live a health life until 100 they will put retirement age up to 90.
  • by NetFusion ( 86828 ) on Friday March 24, 2017 @08:47AM (#54101627)

    2015 - A Periodic Diet that Mimics Fasting Promotes Multi-System Regeneration, Enhanced Cognitive Performance, and Healthspan
    http://www.cell.com/cell-metab... [cell.com]

    2016 - Fasting: Awakening the Rejuvenation from Within | Valter Longo | TEDxEchoPark
    https://www.youtube.com/watch?... [youtube.com]

    2017 - Fasting-Mimicking Diet Promotes Ngn3-Driven -Cell Regeneration to Reverse Diabetes
    http://www.cell.com/cell/fullt... [cell.com]

    You can replicate the study at home with 4 days of a ketogenic fasting mimic diet every 10 days for six cycles with a %5 carb ( 20 net carbs of nuts/greens/dairy) / %75 fat (nuts/olives/fish/eggs/butter) / %20 protein (nuts/fish/eggs/greens/bacon) macro and 50% then 20% , 20% , 20% calorie restriction (the 3 day 10% restriction of the study on mice was extreme and not for the faint of heart). Throw in multi vitamin and probiotic day 3 and 4 and lots and lots of water with pinch of salt now and then/mineral water/coffee/tea during the fast and... amazing. You lose fat, feel better, and if the studies are right; get some nice anti-cancer, anti-aging, anti-disease, body regeneration benefits.

    • by emil ( 695 )

      About a year ago it was discovered that the common dietary substance quercetin is able to kill senescent endothelial cells in the gi tract.

      http://onlinelibrary.wiley.com/doi/10.1111/acel.12344/abstract [wiley.com]

      By transcript analysis, we discovered increased expression of pro-survival networks in senescent cells, consistent with their established resistance to apoptosis. Using siRNA to silence expression of key nodes of this network, including ephrins (EFNB1 or 3), PI3K, p21, BCL-xL, or plasminogen-activated inhibi

  • by Anonymous Coward

    "Such genetic alterations aren't practical for people"

    I have two possible thoughts on this:

    1) Then you should stop wasting your time on this research and spend your time elsewhere, and

    2) Why would this not be practical for people? You can make it happen in mice, but not people? You couldn't give parents an option of assisted fertility (match an egg and sperm from the couple together that have been modified in some way) with these benefits for the child? Of course it isn't practical for people already alive,

  • If old cells can't reproduce due to lack of telomerase, and all the old cells are then killed. What's left?

    And before you talk about just artificially lengthening telomeres, remember that they are essentially an anti-cancer safeguard. The combination of both will produce mutant cancerous zombies.

    • I'm 64 - all my cells are old.
      It might be like suicide for me. :)
    • If all your cells were senescent you'd be on death's door anyhow.
      • Killing off those cells early would bring you closer - but just make you feel better while it happens.

        • Well, no... your tissues will be regenerated with various stem cells like normal repair. You've just cleaned out the cruft of the senescent cells. If you had no stem cells and all your cells were senescent, you'll be dead in a week whether you kill them with a treatment like this or not.
  • They can kill healthy cells or trigger side effects such as a drop in the number of platelets, the cellular chunks that help our blood clot.

    50 years from now, the world is populated by >100-year-old people who are afraid to prick their finger for fear of bleeding out.

  • People living longer will make Social Security, Medicare and Medicaid bomb out even sooner.

  • by Quirkz ( 1206400 ) <ross.quirkz@com> on Friday March 24, 2017 @10:17AM (#54102183) Homepage

    For me, the following was one of the more interesting pieces:

    Senescent cells carry the type of DNA damage that should spur a protective protein, called p53, to put them down. Instead, the researchers found that a different protein, FOXO4, latches onto p53 and prevents it from doing its duty. To counteract this effect, De Keizer and colleagues designed a molecule, known as a peptide, that carries a shortened version of the segment of FOXO4 that attaches to p53.

    Does this mean we have an internal cleanup mechanism, but somehow it's gotten subverted over the years? Our ancestors may have had the benefit of p53, until something changed and we started developing FOXO4 when we hadn't before? Or somewhere along the line the amount of FOXO4 in our bodies increased? That seems fascinating to me.

    My first reaction was also to think, "That doesn't seem like a very useful mutation/bit of evolution" but of course most of the age-related stuff won't be important until you're beyond the age of reproduction, so it's probably relatively easier for that kind of problem to sneak in than something that affects the young. I also wonder if it's *just* a mutation, or if the FOXO4 is doing something else more useful for us when we're young, that the tradeoff is worth it?

    • From a purely mathematical resource point of view, older specimens of a species take up resources that could be better used by younger, reproducing, members of the species. It makes sense that there exists a mechanic to have these older specimens die off after they are no longer useful to the survival of the species to preserve the resources for the younger generations.

      It probably wasn't until later that the older specimens became useful to the survival of the species by teaching the younger generations th

      • From a purely evolutionary standpoint you are correct, but I disagree from an energy/resource standpoint. Raising children is very expensive and resource intensive. Once you get over the reproductive hill most people start to tend toward frugal living. So for the same population a state of 'less children but living longer' is easier on the environment.
        All first world countries are experiencing a shrinking demographic and it make sense to help people live longer productive lives.
        • by PPH ( 736903 )

          Once you get over the reproductive hill most people start to tend toward frugal living.

          Not in my town. They buy Cadillacs. And then bend them, buy another one, etc., etc. ....

          • A payment on a car is a lot cheaper than having kids. Trust me I know :-)
            • You gave birth to a car?

              You sure you didn't just swallow a Hot Wheels or a Matchbox one? Perhaps while drunk?
              Did it grow? Or did it remain Matchbox-size?

    • All mammalian cells are constantly producing p53, and disposing of it. When they stop, repair or suicide should occur.

      https://en.wikipedia.org/wiki/TP53 [wikipedia.org]

      Once activated, p53 will induce a cell cycle arrest to allow either repair and survival of the cell or apoptosis to discard the damaged cell. How p53 makes this choice is currently unknown... First, the half-life of the p53 protein is increased drastically, leading to a quick accumulation of p53 in stressed cells. Second, a conformational change forces p53

    • FOXO4 is a complex, complex protein [wikipedia.org]. In some cases it prevents cancer. In other cases, it extends longevity. Apparently in this case it somehow makes you look old. I have no explanation for that, but maybe no one does?
    • Does this mean we have an internal cleanup mechanism, but somehow it's gotten subverted over the years?

      You're making the assumption here that living a very long time was the goal. It isn't.

      Evolution optimizes around having the "best" grandchildren. In species that reproduce sexually, frequent mixing of genomes is the primary source of variation, and thus selection for "best". In order to avoid exhausting local resources, the old have to die to free up resources for later generations.

      But with the relatively small number of children humans produce, that death ideally happens after the grandchildren are rela

    • My first reaction was also to think, "That doesn't seem like a very useful mutation/bit of evolution" but of course most of the age-related stuff won't be important until you're beyond the age of reproduction

      It's been common to think of aging as a process of "accumulation of insults" that eventually leads to loss of function. After all, we have a number of extremely long lived cell types (e.g. CNS neurons, pancreatic beta cells, etc.). However, recently it's been clearer and clearer that aging is a deliberate, regulated cellular program. Emphasis because, individual cells (and single celled organisms) also age. Probably the evolutionary explanation lies more with the sacrifices needed for multicellularity, and/

    • P53 is always present in cells but needs to be activated. Basically it's on standby to quickly kill cells in case there's DNA damage(very bad=cancer usually), so FOX helps keep it from killing healthy cells. On a side note peptides tend to get a lot of scrutiny from drug companies/designers. Our bodies readily metabolize peptides, so drug stability/delivery issues are usually the kiss of death for peptide drugs. Also, senescence is a good thing. Senescent cells don't actively divide, the alternative is mito
  • ...you stop aging in it's tracks.

  • Let's see... (Score:4, Insightful)

    by MrKrillls ( 3858631 ) on Friday March 24, 2017 @01:14PM (#54103539)

    Kill off all my elderly brain cells:

    a) Pretty much nothing left in my head.

    b) Nobody will notice any change.

  • Death really is unnecessary from an evolutionary standpoint. We have grown beyond the need to pass on genetic traits that allow us to adapt to changing environments since mankind uses technology to do this. Medicines are preventing the need to evolve immunities naturally so the fact that we die is simply the product of inefficiencies on cellular replication. The three things needed for immortality are negative apoptosis, efficient waste removal, and efficient genetic error checking. There is no need for t
    • I find it intriguing that you think evolution should have a say in this.

      Because evolution has a destination in mind or cares about us or what exactly?
    • Death really is unnecessary from an evolutionary standpoint. We have grown beyond the need to pass on genetic traits that allow us to adapt to changing environments since mankind uses technology to do this.

      That makes death unnecessary for humans to adapt. Death is still necessary from an evolutionary standpoint.

      Without death, why reproduce? Without sexual reproduction, we don't mix our genomes. No mixing of genomes, no selection.

      So death is still necessary for evolution. Technology just means we have additional options for adaptation besides evolution.

      • Why do we need to adapt? For modern man, reproduction is merely a byproduct is a recreational activity. Humanity creates diversity for no environment need that science can't over come. We are not having babies for the survival of the species or even the survival of a family bloodline. If death becomes obsolete, the next question will be the need for children, at least at the current rate.
  • What kind of cake is that? It is a cellular peptide cake. [wikia.com]

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