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

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.

Comments

So ... what can I hope for?

[Opportunist]

More hair and better kidney function?

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

Re:So ... what can I hope for?

[LifesABeach]

Imagine the Koch brothers are given this drug, and nobody else.

Lab Rats have it made

[SCVonSteroids]

We're finding all these awesome ways to extend and enrich their lives. God I wish I was a rat...

Re:Lab Rats have it made

[PolygamousRanchKid]

God I wish I was a rat...

You might want to think about that wish again. Scientific studies have proven time and again that the leading cause of death among rats is lab scientists.

Re:Lab Rats have it made

[SCVonSteroids]

So we must band together as one, and oust these damned scientists once and for all!

Re:Lab Rats have it made

[micahraleigh]

I'm sure collective negotiations are very compelling to scientists.

Re:Lab Rats have it made

[denzacar]

Are you pondering what I'm pondering?

Sounds nice!

[Kokuyo]

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?

Re:Sounds nice!

[Lennie]

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?...

Re:Sounds nice!

[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 batteries managed to do at the age of 94..

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.

Re:Sounds nice!

[rmdingler]

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.

Re:Sounds nice!

[nalik89]

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!

[bluefoxlucid]

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.

Re:Sounds nice!

[Nemyst]

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.

Re:Sounds nice!

[gurps_npc]

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 = poverty = deaths caused by: famine, disease, drought, war, crime, etc. (all symptoms of resource scarcity).

It is true that recently (in the past two hundred years) birth control and capitalism combined with a larger enough population for scientific research has led to far better resource management and expansion. That is a recent phenomena and NOT related to resource scarcity. That is, science ameliorates the problem you describe, but it is NOT an automatic solution.

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

Re:Sounds nice!

[Immerman]

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.

Re:Sounds nice!

[drew_kime]

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

Just like closet space.

Re:Sounds nice!

[Fire_Wraith]

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 leading edge of the bad affects of that (such as Japan), even if it's not a long term fix.
More importantly though, people who are less frail can also work more, so you might see retirement pushed back a ways to compensate (especially if we're living longer as a result).
(Cynical thought: "And you thought age-based discrimination in IT was bad now.")

As for your Cynical thought, hey, why not? It's already a sci-fi book plot, after all: https://en.wikipedia.org/wiki/...

Re:Sounds nice!

[bluefoxlucid]

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 have to have 18 kids to ensure 2 survive polio and malaria--and have a population limited by availability of things like food.

In America and Europe, the population spiked around the 1920s. There was food scarcity, and so a lot of Nobel-Prize-winning work went into developing new agricultural tools and methods. In a world with 1.9 billion people and an add of around 100 million per year, we suddenly saw growth to 3.2 billion people in less than a decade as food became more-accessible.

So yes, historically, this is how it works. Not how it might work; not how it works with foxes and lemmings; this is how it works with people, throughout human history.

Also, people are rational agents; they simply don't always have 100% of all information available. They make a rational decision based on imperfect information.

Re:Sounds nice!

[bluefoxlucid]

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 not spent the past 10,000 year of human history dictating how many children each family shall have to properly manage global resources; we've just expanded until maximum.

That means, yes, we expand until scarcity. We expand until the cost to acquire food starts increasing. We advance until the number of farmers needed grows proportionally-faster than the number of people being born. We expand until we can't build houses fast enough to house all these people, can't mine oil fast enough to provide all the industrial services they need, and so forth. Then we get more poor people and continued expansion necessarily will cause a rise in unemployment, a rise in poverty, and a visible and obvious economic recession, which slows population growth.

Re:Sounds nice!

[bluefoxlucid]

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

Re:Sounds nice!

[avandesande]

Most developed nations are undergoing a shrinking demographic. People having less children and living longer is more efficient and environmentally friendly than the opposite.

Re:Sounds nice!

[boristdog]

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.

Re:Sounds nice!

[fahrbot-bot]

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 /.)

Re:Sounds nice!

[parkinglot777]

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...

Re:Sounds nice!

[parkinglot777]

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 of their kids may never become adults (die). It is more self-center thought, but it is still rational and comes from a different angle of point of view...

Re:Sounds nice!

[Megol]

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 extreme amounts. But that isn't a real problem, the world have always changed and we have changed with it.

Resources are available - we just need to learn to use them wisely even if that means moving people to other locations instead of e.g. settling in a desert environment and transporting water, food and electricity for watering grass, overeating in the extreme and cooling inefficient buildings.

Re:Sounds nice!

[Anonymous Coward]

People tend to rely heavily on heuristics to reduce the amount of high-cost thinking they have to do. That's also a rational decision, and it limits the rationality of their other decisions.

Re:Sounds nice!

[ragahast]

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

Just look at the data.

The main reason behind the dramatic decline in children per woman, even in developed countries, is probably the similarly dramatic improvement 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.

Re:Sounds nice!

[CrimsonAvenger]

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.

Re:Sounds nice!

[Immerman]

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 almost any price, so a relatively cheap and powerful aid to that goal would probably find a huge market, even if it did also accelerate the return to a more sane relationship with death.

Even then though, I would not be surprised if death from "old age" remained extremely uncommon, with people instead continuing to take the anti-agapics as long as possible, and then choosing a more pleasant way to go when they decide their time is up. I mean it's basically a choice between decaying as slow as possible and then taking a leap of faith when it's no longer worth it, versus willfully letting the misery of decay accelerate until it kills you.

Re:Sounds nice!

[GameboyRMH]

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.

Re:Sounds nice!

[bluefoxlucid]

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 growth.

Re:Sounds nice!

[vandamme]

Shit, we already went to war over Iraqi oil.

Re:Does it work for meth heads too?

[Lennie]

Well, are you off the meth ?

It caused problems in the Red Mars trilogy

[swb]

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:Research to extend lifespans should be banned

[arobatino]

Countries with longer lifespans have lower population growth, or even decline. This is plausible because people in those countries don't have to have extra children to be certain that some will survive. If life extension also increases the maximum reproductive age, people could put off having children which would reduce population growth even more. A lot of people in developed countries only choose to have children because their biological clock is ticking.

Re:Research to extend lifespans should be banned

[Nutria]

Correlation or causation?

After all, education and prosperity are in that mix too.

Re:Does it work for meth heads too?

[butchersong]

Buy an axe, a 22 rifle, a shovel, a backpack and a pot. Find a large national park: https://www.nps.gov/index.htm and see if you can survive for a few years on your own.

If this allows you to live a health life until 100

[Chrisq]

If this allows you to live a health life until 100 they will put retirement age up to 90.

Fasting Mimicking Diet does this safely

[NetFusion]

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

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

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

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.

Not practical for people?

[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, but if you ever want to solve the "aging" problem, you're probably going to have to break (modify) a few eggs (ovum).

Man scientists don't think in cool ways any more, and/or people are terrified of GMOs, which is just stupid. One day we might have superhumans from genetic modifications living the most amazing lives humans could ever live, and there will still be some idiot hipster who says, "I just don't know, man, I think that genetic modification that's making us live to 350 without any negative side effects is like, killing us, man. Here, try this kale enema, it's great."

Kills all old cells...eventually kills all cells

[omnichad]

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.

SciFi plot

[drew_kime]

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.

FDA will kill it

[BoRegardless]

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

Broken cleanup mechanism?

[Quirkz]

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?

Re:Broken cleanup mechanism?

[Quince alPillan]

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 through experience or serving another purpose that benefits the species, such as taking care of the young or defending against predators. Many species have all three traits, so it was likely evolved very early on for multicellular life.

Re:Broken cleanup mechanism?

[avandesande]

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.

Re:Broken cleanup mechanism?

[PPH]

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. ....

Re:Broken cleanup mechanism?

[avandesande]

A payment on a car is a lot cheaper than having kids. Trust me I know :-)

Re:Broken cleanup mechanism?

[phantomfive]

FOXO4 is a complex, complex protein. 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?

Re:Broken cleanup mechanism?

[jeff4747]

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 relatively well-established. Grandma and grandpa take some of the workload off the parents for raising our nearly helpless newborns. But after the grandkids can help gather with the adults, the grandparents are not nearly as beneficial. So they die.

Re:Broken cleanup mechanism?

[ragahast]

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/or population dynamics of cells, rather than of whole, multicellular organisms.

if the FOXO4 is doing something else more useful for us when we're young

It prevents cancer. FOXO4 is a transcription factor that activates transcription of P27, a CDK inhibitor that prevents cells from progressing through the cell cycle. FOXO4 itself is a target of PI3K and Akt, kinases which attach phosphate groups to FOXO4 and prevent its translocation to the nucleus, and thus transcription of FOXO4 regulated genes. Since FOXO4 favors cell cycle progression, this tends to permit cells to advance through the cell cycle and proliferate.

PI3K and Akt are important components of pathways for nutrient sensing, regulation of growth and proliferation, and protein production and degradation. They frequently have activating mutations in cancer, contributing to runaway division. In many ways, cancer and aging/neurodegeneration are actually flip sides of the same coin. Cancer cells tend to have hyperactive homeostasis mechanisms that boost protein stability and buffer the destabilizing effects of the mutations they accumulate, as well as allowing the runaway growth, etc. In contrast, old cells (especially degenerating neurons) have compromised homeostasis mechanisms, leading to increased protein misfolding and reduced degradative capacity, which in turn cause loss of function and inability to replicate and grow as these misfolds build up in the cell.

Here's a partial map of some of these pathways, centered on the mTOR regulatory hub (you can pick out Akt, PI3K and FOXO1, though FOXO4 is missing). Clearly, these are extremely complex regulatory networks, which we are only just beginning to understand, that exist to strike a delicate balance between growth and stability within a multicellular alliance that itself exists in a context of worldly struggle. As we develop technology to manipulate these regulatory networks, we will also have to learn how these networks are altered in aging and disease in order to understand when - and if - medical interventions can safely restore that balance.

Source/disclaimer: I am a PhD student in Biophysics.

Re:Broken cleanup mechanism?

[denzacar]

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?

If you kill enough cells...

[sandmaninator]

...you stop aging in it's tracks.

Re:Kills all old cells...eventually kills all cell

[reboot246]

I'm 64 - all my cells are old.
It might be like suicide for me. :)

Let's see...

[MrKrillls]

Kill off all my elderly brain cells:

a) Pretty much nothing left in my head.

b) Nobody will notice any change.

Quercetin

[emil]

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

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 inhibitor-2, killed senescent cells, but not proliferating or quiescent, differentiated cells. Drugs targeting these same factors selectively killed senescent cells. Dasatinib eliminated senescent human fat cell progenitors, while quercetin was more effective against senescent human endothelial cells and mouse BM-MSCs. The combination of dasatinib and quercetin was effective in eliminating senescent MEFs. In vivo, this combination reduced senescent cell burden in chronologically aged, radiation-exposed, and progeroid Ercc1/ mice. In old mice, cardiac function and carotid vascular reactivity were improved 5 days after a single dose.

Death really is unnecessary

[Tempest451]

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 the skin cells you have at 50 to be any different than at 20.

Re:Death really is unnecessary

[micahraleigh]

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?

Re:Death really is unnecessary

[jeff4747]

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.

Re: Death really is unnecessary

[Tempest451]

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.

No. p53 - the guardian of the genome.

[emil]

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

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 to be activated as a transcription regulator in these cells....

Re:Research to extend lifespans should be banned

[Kjella]

Correlation or causation? After all, education and prosperity are in that mix too.

Mostly correlation I think. The whole "have enough kids that some grow up" is driven by need, not love. It's not like parents consider them replaceable as human beings as if they have a spare. The need to have your kids support you in your old age is primarily economic, if you have a public system you get help and if you have private money you can hire help. So prosperity -> money for care of elderly, healthcare -> lower child deaths -> double effect of lower risk and less need. I think that's also why there's such a delay and population bulge in the transition, people have to see that hey these people had two kids and they're doing okay now as elderly, do we really need five more?

Lt Cmdr Data

[q4Fry]

What kind of cake is that? It is a cellular peptide cake.

Re:Lt Cmdr Data

[denzacar]

Captain being French, it's no wonder there was so much menage a Troi on Enterprise.

Re:Kills all old cells...eventually kills all cell

[Gilgaron]

If all your cells were senescent you'd be on death's door anyhow.

New drugs kill elderly cells while slashdot dreams

[micahraleigh]

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 government imposed solution for anti-aging drugs?

200 years ago when 95%+ of the population were farmers I can see how you could make the case that we had resource problems. Let me be the first to tell you we've 1st world problems today.

Re:Research to extend lifespans should be banned

[micahraleigh]

What about population shrinkage? Europe and Japan are losing population and the US is not growing.

Population growth is an imaginary problem.

Re:Kills all old cells...eventually kills all cell

[omnichad]

Killing off those cells early would bring you closer - but just make you feel better while it happens.

Re:Research to extend lifespans should be banned

[iMadeGhostzilla]

As of late I'm not sure there is such a thing as causation in any complex (human, biological) system, for anything that takes long enough time to manifest.

Sure if you drink poison it will kill you instantly. But if you eat bacon every day will that *cause* a heart disease 40 years after you started? And even in the case of poison it depends -- apparently if you take a small amount of poison regularly it will make you more resistant to that poison (the process is called "hormesis"). Thought it maybe screws up the heart. :-| (Note I'm implying a causation in that sentence.)

Correlation comes from our measurements of the real world. Causation comes from our mental model of that real world, which is never absolute ("the map is not the territory") -- meaning there's always a deep enough level where the model will fail, and in complex systems our models are generally poor.

I think causation is a mental crutch to help us navigate the world of patterns around us but should not be thought of "real."

Re:Kills all old cells...eventually kills all cell

[Gilgaron]

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.

Re:Research to extend lifespans should be banned

[Nutria]

I think causation is a mental crutch to help us navigate the world of patterns around us but should not be thought of "real."

You say this just after you wrote, "if you drink poison it will kill you instantly."

You are on to something though. I'd say, "we use 'weakly founded' assertions of causation as a crutch to help us navigate the world of patterns around us." IOW, we stereotype everything all the time, because we just can't individually analyze every person and every circumstance.

Not broken

[omaha393]

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 mitotic cells that do divide. More divisions you have, more likely it is cancer forms. So as always, cancer and aging are inseparable and we're all doomed :)

Re:Kills all old cells...eventually kills all cell

[omnichad]

Right. More forced replication, faster depletion of stem cells.

There's always bullets...

[denzacar]

Just ask Denis Voronenkov.

Re:This mollecule have side effects on humans ...

[denzacar]

Sounds like the mouse problem UK had back in the '70s.

Re:Research to extend lifespans should be banned

[iMadeGhostzilla]

I agree, it's like causation is a fuzzy thing, that fades over time as the involvement of complex processes increases. Which leads to the conclusion that causation is just an appearance in our minds, which are constantly constructing and reconstructing the map of reality.

Which in a sense is obvious -- causation exists only within the mental model by definition, and mental models exist only in the mental domain by definition. (Even the term "to exist" is a thought construct, meaningless outside of a mental model.) Causation is a mind illusion about processes in the outside world, stable at short times or simple processes and deceiving at longer times and/or complex processes. Stable as in useful, i.e. you can rely on it for decision making, and vice versa.

Re:Research to extend lifespans should be banned

[Nutria]

causation exists only within the mental model

You try and stretch the concept too far, given that there obviously are proximate causes.

Re:Kills all old cells...eventually kills all cell

[Gilgaron]

Depleting your stem cells to yield improved organ function is a net positive for your life span, however.