Daily Archives: May 4, 2017

Cancer-causing virus masters cell's replication, immortality Science Daily In a paper appearing in the open access journal eLife, a team of researchers from Duke's School of Medicine details just how the Epstein-Barr virus manages to persist so well inside the immune system's B cells, a type of white blood cell that is ... and more »

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Cancer-causing virus masters cell's replication, immortality - Science Daily

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Viruses are notorious for taking over their hosts operations and using them to their own advantage. But few human viruses make themselves quite as cozy as the Epstein-Barr virus, which can be found in an estimated 9/10 humans without causing any ill effects. That is, until this virus causes mononucleosis in adolescents or various cancers of the lymph nodes, including Hodgkins and non-Hodgkins lymphomas, in immune compromised people.

A team of researchers from Dukes School of Medicine details just how the Epstein-Barr virus manages to persist so well inside the immune systems B cells, a type of white blood cell that is normally responsible for recognising and responding to foreign invaders.

The challenge is that its a really efficient pathogen, and evades the hosts immune system well even when its recognised as an invader,

said Micah Luftig, an associate professor of molecular genetics and microbiology and investigator on the new study.

Luftigs team has found that with a few select chemical signals used early in the course of an infection, Epstein-Barr mimics the beginning of the B cells normal response to an infectious agent. From within, the virus manages to ramp up the B-cells reproduction of itself, while at the same time helping the cell resist its own self-destruct signals.

The virus actually taps into the B cells normal protection against apoptosis, the programmed cell death that takes B cells out of circulation, Luftig said.

Once the infection is established, Epstein-Barr prefers to hide out in what are known as memory B cells, relatively slowly reproducing cells that circulate throughout the body. All of this is about establishing latency, Luftig said, or the ability to hide quietly in plain sight.

Using a new technique developed elsewhere called BH3 profiling that allowed them to test the critical cellular pro- and anti-apoptosis proteins individually, the team was able to see which of these the virus was controlling and then watch the transition from an uninfected cell to the active early infection phase to the latent infection in an immortal cell. The key piece theyve uncovered is a viral protein called EBNA3A which manages apoptosis resistance in infected B cells.

The risk for cancers is largely an issue if youre immune suppressed, Luftig said. But, for example, a recent National Cancer Institute study found that children who receive organ transplants have a 200-times higher chance of getting Non-Hodgkins Lymphoma, one of the cancers caused by Epstein-Barr.

The team thinks BH3 profiling could prove useful in guiding treatment decisions on Epstein-Barr associated cancers such as these.

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Cancer-causing virus masters cell's replication & immortality - Drug Target Review

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Scientists develop novel chemical 'dye' to improve liver cancer imaging Science Daily A research team led by Assistant Professor Edward Chow (right), Principal Investigator from the Cancer Science Institute of Singapore at NUS and Department of Pharmacology at NUS Yong Loo Lin of Medicine, has developed a novel nanodiamond-based ... and more »

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Scientists develop novel chemical 'dye' to improve liver cancer imaging - Science Daily

We all grow old. We all die.

For Aubrey de Grey, a biogerontologist and chief science officer of the SENS Research Foundation, accepting these truths is, well, not good enough. He decided in his late twenties (hes currently 54) that he wanted to make a difference to humanity and that battling age was the best way to do it. His lifes work is now a struggle against physics and biology, the twin collaborators in bodily decay.

He calls it a war on age.

Grey considers aging an engineering problem. The human body is a machine, he told me in the following interview, and like any machine, it can be maintained for as long as we want.

This is not an isolated view. There is a broader anti-aging movement afoot, which seems to be growing every day. As Tad Friend describes colorfully in a recent New Yorker essay, millions of venture capital dollars are being dumped into longevity research, some of it promising and some of it not. Peter Thiel, the billionaire co-founder of PayPal, is among the lead financiers (hes a patron of Greys organization as well).

Greys work is particularly interesting. For too long, he argues, scientists have been looking for solutions in all the wrong places. There is no monocausal explanation for aging. We age because the many physical systems that make up our body begin to fail at the same time and in mutually detrimental ways.

So hes developed what he calls a divide-and-conquer strategy, isolating the seven known causes of aging and tackling them individually. Whether its cell loss or corrosive mitochondrial mutations, Grey believes each problem is essentially mechanical, and can therefore be solved.

But even if this Promethean quest to extend human life succeeds, several questions persist.

If we develop these anti-aging technologies, who will have access to them? Will inequality deepen even further in a post-aging world? And what about the additional resources required to support humans living 200 or 300 or 500 years? The planet is stretched as it is with 7 billion people living roughly 70 years on average (women tend to live three to five years longer than men) and is already facing serious stresses around food, water, and global warming going forward.

Grey, to his credit, has thought through these problems. Im not sure hes alive to the political implications of this technology, specifically the levels of state coercion it might demand.

But when pressed, he defends his project forcefully.

Is there a simple way to describe theoretically what the anti-aging therapies youre working on will look like what theyll do to or for the body?

Oh, much more than theoretically. The only reason why this whole approach has legs is because 15 or 17 or so years ago, I was actually able to go out and enumerate and classify the types of damage. We've been studying it for a long time, so when I started out in this field in the mid-90s so I could learn about things, I was gratified to see that actually aging was pretty well understood.

Scientists love to say that aging is not well understood because the purpose of scientists is to find things, out so they have to constantly tell people that nothing is understood, but it's actually bullshit. The fact is, aging is pretty well understood, and the best of it is that not only can we enumerate the various types of damage the body does to itself throughout our lives, we can also categorize them, classify them into a variable number of categories

So I just talked about seven categories of damage, and my claim that underpins everything that we do is that this classification is exhaustive. We know how people age; we understand the mechanics of it. There is no eighth category that were overlooking. More importantly, for each category there is a generic approach to fixing it, to actually performing the maintenance approach that I'm describing, repairing the damage.

Can you give me an example of one of these categories and what the approach to fixing it looks like?

One example is cell loss. Cell loss simply means cells dying and not being automatically replaced by the division of other cells, so that happens progressively in a few tissues in the body and it definitely drives certain aspects of aging. Let's take Parkinson's disease. That's driven by the progressive loss of a particular type of neuron, the dopaminergic neuron, in a particular part of the brain.

And what's the generic fix for cell loss? Obviously it's stem cell therapy. That's what we do. We preprogram cells in the laboratory into a state where you can inject them into the body and they will divide and differentiate to replace themselves that the body is not replacing on its own. And stem cell therapy for Parkinson's disease is looking very promising right now.

Is it best to think of aging as a kind of engineering problem that can be reversed or stalled?

Absolutely. It's a part of technology. The whole of medicine is a branch of technology. It's a way of manipulating what would otherwise happen, so this is just one part of medicine.

But you're not trying to solve the problem of death or even aging, really. Its more about undoing the damage associated with aging.

Certainly the goal is to undo the damage that accumulates during life, and whether you call that solving aging is up to you.

What would you say is your most promising line of research right now?

The great news is that we have this divide-and-conquer strategy that allows us to split the problem into seven subproblems and address each of them individually. That means we're constantly making progress on all of them. We pursue them all in parallel. We actually don't pursue stem cell therapy very much, simply because so many other people are doing it and basically everything really important is being done by somebody else, so it's not a good use of our money.

We're a very small organization. We only have $4 million a year to spend, so we're spread very thin. We're certainly making progress. Over the past year we've published really quite high-profile papers relating to a number of main research programs, so there's no really one thing that stands out.

What do you say to those who see this as a quixotic quest for immortality, just the latest example of humanity trying to transcend its condition?

Sympathy, mainly. I understand it takes a certain amount of guts to aim high, to actually try to do things that nobody can do, that nobody's done before. Especially things that people have been trying to do for a long time. I understand most people don't have that kind of courage, and I don't hate them for that. I pity them.

Of course, the problem is that they do get in my way, because I need to bring money in the door and actually get all this done. Luckily, there are some people out there who do have courage and money, and so we're making progress.

Ultimately, the fact is aging has been the number one problem of humanity since the dawn of time, and it is something that, until I came along, we have not had any coherent idea how to address, which means the only option available to us has been to find some way to put it out of our minds and find a way to get on with our miserably short lives and make the best of it, rather than being perpetually preoccupied with this ghastly thing that's going to happen to us in the relatively distant future. That makes perfect sense. I don't object to that.

The problem is that suddenly we are in a different world where we are in striking distance of actually implementing a coherent plan that will really work, and now that defeatism, that fatalism, that resignation, has become a huge part of the problem, because once you've made your peace with some terrible thing you know, it's very hard to reengage.

Are there any ethical questions or reservations that give you pause at all?

Not at all. Once one comes to the realization that this is just medicine, then one can address the entire universe of potential so-called ethical objections in one gut. Are you in favor of medicine or not? In order to have any so-called ethical objection to the work we do, the position that one has to take is the position that medicine for the elderly is only a good thing so long as it doesn't work very well, and thats a position no one wants to take.

Ive no doubt youve been asked this question before, but I think its too important to gloss over. You talk enthusiastically about transitioning to a post-aging world, but there are many people who worry about what it means to increase the humans time on earth. We dont necessarily have an overpopulation problem, but we certainly have an inequality problem, and we seem to need more resources than we have. If 90 percent of people die from aging now, and suddenly people are living for 200 or 300 years, how will we be able to sustain this kind of growth?

First of all, thank you for prefacing the question with the thought that I've probably heard this question a lot, because of course I have. But you'd be astonished at how many people have presented this question to me starting with, "Have you ever thought of the possibility that..." as if they genuinely had a new idea.

But yes, overpopulation is the single biggest concern that people raise, and I have basically three levels of answers to these questions. First, the answer is specific to the individual question. So in the case of overpopulation, essentially I point to the fact that fertility rates are already plummeting in many areas. And people often forget: Overpopulation is not a matter of how many people there are on the planet but rather the difference between the number of people on the planet and the number of people that can be on the planet with an acceptable level of environmental impact, and that second number is of course not a constant; it's something that is determined by other technologies.

So as we move forward with renewable energy and other things like desalinization to reduce the amount of pollution the average person commits, we are increasing the carrying capacity of the planet, and the amount of increase that we can expect over the next, say, 20 years in that regard far exceeds what we could expect in terms of the trajectory of rise in population resulting from the elimination of death from aging. So that's my main answer.

The second level of answer is at the level of sense of proportion. Technology happens or doesn't happen, whatever the case may be, and maybe the worst-case scenario is that we will end up with a worse overpopulation problem than what we have today.

What does that actually mean? It means we're faced with a choice in a post-aging world, in a world where the technology exists a choice between either, on the one hand, using these technologies and having more people and having fewer kids than we would like or, on the other hand, letting stuff go on the way it is today, which involves not using technology that will keep people healthy in old age and therefore alive.

Ask yourself, which of those two things would you choose? Would you choose to have your mother get Alzheimer's disease or to have fewer kids? It's a pretty easy choice, and people just don't do this.

The third level is perhaps the strongest of all, which is that it's about who has the right to choose. Essentially if we say, Oh, dear, overpopulation, let's not go there. Let's not develop these technologies, then what we are doing as of today is we are delaying the arrival of our technology. Of course it will happen eventually. The question is how soon? That depends on how hard we try.

If we know that, then what we're doing is we're delaying the arrival of the technology and thus condemning a whole cohort of people of humanity of the future to the same kind of death and disease and misery that we have today in old age, when in fact we might have relieved that suffering had we developed the therapies in time.

I dont want to be responsible for condemning a vast number of people to death. I dont want to be in that position. I think theres a strong argument that we should get on developing these technologies has quickly as we can.

I take your points there, but those questions are far easier to answer in theory than they are to solve in practice. For instance, we cant simply decide that people will have fewer children without potentially dangerous levels of state coercion. The politics of this is complicated at best, dystopian at worst.

In any event, let me at least raise one more concern. What is your sense of the cost and the accessibility of these therapies should they become available? People concerned with bioengineering, for example, worry that technologies like this, if they arent equally distributed, will produce inequalities of the sort weve never seen before and cant sustain.

Its a valid concern. It needs to be addressed, but luckily, like the overpopulation one, it's a really easy one to address. Today what we see with high-tech medicine is that it is even in countries with a single-payer system it's pretty much limited by the pay because there's only so much resources available.

But part of the problem now is that our current therapies for elderly people dont work well. It postpones the ill health of old age by a very small amount if we're lucky, and then people get sick anyway, and we spend all the money that we would have spent in absence of the medicine just keeping the person alive for a little longer in a miserable state.

Now compare that with the situation where the medicine actually does work, where the person actually stays healthy. Yes, they live a lot longer, and sure enough, it may be that we have to supply these therapies multiple times because they are inherently periodic therapies, so we could be talking about a substantial amount of money. But the thing is these people would be healthy, so we would not be spending the money on the medicine for the sick people that we have today.

Plus, on top of that, there would be massive indirect savings. The kids of the elderly would be more productive because they wouldn't have to spend time looking after their sick parents. The elderly themselves would still be in an able-bodied state and able to actually contribute wealth to society rather than just consuming wealth.

Of course, there are lots and lots of big uncertainties in these kinds of calculations, but there is absolutely no way to do such a calculation that does not come to the absolutely clear conclusion that the medicines would pay for themselves many times over, really quickly.

So what that means, from the point of view of government setting aside the fact that it would be politically impossible not to support this is that it would be suicidal from a purely mercenary economic point of view not to do this. The country will go bankrupt because other countries will be making sure their workforce is able-bodied. The world will be frontloading their investments to ensure that everybody who is old enough to need them will get these therapies.

When will the therapies youre developing be ready for human experimentation?

That will happen incrementally over the next 20 years. Each component of the SENS panel will have standalone value in addressing one or another disease of old age, and some of them are already in clinical trials. Some of them are a lot harder, and the full benefit will only be seen when we can combine them all, which is a long way out.

How confident are you that someone alive today will not die of aging?

It's looking very good. Of course this is primary technology, so we can only speculate. It's very speculative what the time frame is going to be, but I think we have a 50-50 chance of getting to work on longevity escape velocity, the point where we are postponing the problem of aging faster than time is passing and people are staying one step ahead of the problem. I think we have a 50-50 chance of reaching that point within 20 years of now, subject only to improved funding on the early-stage research that's happening at the moment.

Escape velocity is an interesting analogy. The idea is to keep filling up the biological gas tank before it runs out, staying a step ahead of the aging process?

Right. The point is that these are rejuvenation therapies, which means they are therapies that genuinely turn back the clock. They put the body into a state that is analogous or similar to how it was at an earlier [stage] rather than just stopping or slowing down the clock. Every time you do this, you buy time, but the problem gets harder because the types of damage that the therapy reverses will catch up, and those imperfections just need to be progressively partially eliminated. The idea, then, is that you asymptotically approach the 100 percent repair situation but you never need to get there. You just need to keep the overall level of damage below a certain tolerable threshold.

For more about de Grey's work, visit the SENS website.

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Scientists are waging a war against human aging. But what happens next? - Vox