Scientists one step closer to mimicking caloric restriction with anti-aging drugs

A team of University of Michigan scientists have discovered how a gene's action may help explain why restricting diet lengthens life in animals. The results offer promising early evidence that scientists may succeed at finding targets for drugs that someday could allow people to live longer, healthier lives.

Specifically, they found that suppressing a newly discovered gene lengthens the lifespan of roundworms. We've long known that significantly restricting food intake makes animals live longer, but the goal is to find less drastic ways to achieve the same effect in humans someday.

To find possible avenues for future anti-aging drugs, many scientists are focusing on signaling pathways in cells that sense nutrients. The one examined by the Michigan team, the target of rapamycin pathway or TOR pathway, is so named because its activity can be influenced by the drug rapamycin. Recent results from a large federal study being conducted at U-M and elsewhere have shown that in mice, rapamycin is effective at mimicking the anti-aging effects of dietary restriction.

Research in the last 25 years has shown that animals, including mammals, live longer and have lower levels of certain measures of age-related decline when scientists have restricted their food intake. It's highly suspected that the same effect hold trues for humans, hence the caloric restriction life extension movement.

When calories or certain nutrients are restricted, scientists detect less oxidative damage in animal cells and a slower decline in DNA repair, a decline that normally occurs with age. It's thought that limiting oxidative damage and slowing the decline in DNA repair could help postpone or avoid many age-related diseases.

That said, scientists know relatively little about why reducing food intake causes these effects. In the last 10 years, they have made progress in identifying genes and associated proteins that are suppressed when diet is restricted. By learning more about the cell processes involved, they may be able to discover targets for future drugs that could delay aging without the need to restrict food intake.

Drugs tailored to block specific genes or proteins involved in nutrient-sensing pathways would have much more appeal than reducing what one eats. To achieve anti-aging benefits, it's thought that people would have to restrict food intake by 30 to 40 percent, a grim prospect. In addition, drugs might be designed to avoid other disadvantages of this level of dietary restriction, which include reduced fertility.

C. elegans is a tiny roundworm, a nematode whose two-week lifespan is a great advantage for scientists studying aging. The 1-millimeter-long transparent worms have other advantages, too. C. elegans exhibits many age-associated changes observed in higher organisms. "Many genes identified in C. elegans to control the speed of aging turned out to be evolutionarily conserved, meaning that you can find them in other animals, too. And many are very similar to those found in humans," Ao-Lin Allen Hsu says, lead researcher of the Michigan team.

Hsu and his team created different mutant strains of roundworms, some with drr-2 genes silenced and others in which the gene was over-expressed. They wanted to learn whether inactivating drr-2 is essential for TOR to influence longevity, and found that it was. Other newly discovered genes may affect TOR signaling as well. But Hsu's team has found a promising lead for anti-aging drugs of the future: They were able to show that silencing drr-2's action alone was sufficient to make worms live longer than wild-type C. elegans used as controls.

"It is known that reduction of TOR signaling in response to a change in the environment or genetic manipulation triggers a cascade of cellular signals that alter cell growth, metabolism, and protein synthesis, and decrease the pace of aging," says Hsu. "Our recent studies have shown that drr-2 might play a pivotal role in the TOR signaling network to control protein synthesis as well as longevity."

Regulating access to our own genome data

Trouble brewing: The FDA is looking to put its paws on the nascent direct-to-consumer (DTC) genetic testing industry. The Association feels that some of the genome services are marketing their products as medical tests, and therefore should provide evidence of their efficacy. Since then, both Congress and the Government Accountability Office have looked into the DTC market, raising the prospects for direct government intervention in the market:

On the most basic level, government intervention in this market has the scent of an invasion of privacy. Shouldn't any citizen have the right to know about the contents of his or her own genome? But it's difficult to separate that basic level of knowledge from the medical implications it has, which is where safety, accuracy, and privacy issues—and government enforcement of them—come in.

Link

Book: Choosing Tomorrow's Children

Just added this to my ever growing must-read list: Choosing Tomorrow's Children: The Ethics of Selective Reproduction by Stephen Wilkinson. Here's an excerpt from Iain Brassington's excellent review:

In Choosing Tomorrow's Children, Stephen Wilkinson looks at the ethics of selection, concentrating mainly on 'same number' decisions that we may make. A 'same number' decision is one in which we have chosen to bring a child to birth, but have not decided which. (A 'different number' decision, by contrast, would be one in which we have to choose whether to reproduce at all.) Put another way, he is concerned with choosing between different possible future people (p5). Within this range, though, there's a number of different situations that may give us cause to want to choose: we might be making decisions about choosing an embryo to act as a 'saviour sibling', choosing an embryo to avoid a certain disability, choosing in favour of a (prima facie) disability - as in the case of Candace McCullough and Sharon Duchesneau, who sought specifically to have a deaf child - or choosing one gender over another. Wilkinson spends time considering all these variations on the 'choosing children' theme, and is guided by a presumption of permissibility - a presumption that everything is permitted unless and until it is forbidden, and that the onus is on the person doing the forbidding to make the case for impermissibility.

As far as Wilkinson is concerned, many (if not most) of the arguments that one might mount to establish the impermissibility of choosing children fail. This principle applies even in relation to controversial decisions such as McCullough and Duchesneau's. For in their case, the strongest argument that they would have to face would in all likelihood have to do with the welfare of the child created thereby: that deafness is welfare-reducing, and that it is wrong deliberately to created a child with lower welfare than it might otherwise have enjoyed. Yet, says Wilkinson, even this claim is weak. Partly this has to do with a scepticism about whether choosing for a disability is necessarily the same as choosing for a lower quality of life; partly it has to do with a claim that, even if disabled, people overwhelmingly have a life worth living, and that since this is the only life they could possibly have lived, there is no sense in which they could be said to suffer from a wrongful life; partly it is because the impersonal 'Same Number Quality Claim' - the idea that we ought to select for a higher quality of life whenever possible - does not reliably tell us that all examples of selecting for disability are wrong, and so, even at its strongest, will not tell us that this particular instance of choosing disability is de facto wrong.

Economist: Humanity is about to confront its true nature

Noting the tenth anniversary of the reading of the human genome, The Economist issues a call to action, but not without warning:

Humanity’s foibles will be laid bare. The species’s history, from its tentative beginning in north-east Africa to its current imperial dominion, has already been revealed, just through being able to read the genome. It is now possible, too, to compare Homo sapiens with his closest relative—not the living chimpanzee, with whom he parted company perhaps 5m years ago, but the extinct Neanderthal, a true human. That will do what philosophers have dreamed of, but none has yet accomplished: show just what it is that makes Homo sapiens unique. The genome will answer, too, the age-old question of original sin. By showing what is nature, it will reveal what is nurture—and thus just how flexible and perfectible the human animal really is.
...
Genomics may reveal that humans really are brothers and sisters under the skin. The species is young, so there has been little time for differences to evolve. Politically, that would be good news. It may turn out, however, that some differences both between and within groups are quite marked. If those differences are in sensitive traits like personality or intelligence, real trouble could ensue.

People must be prepared for this possibility, and ready to resist the excesses of racialism, nationalism and eugenics that some are bound to propose in response. That will not be easy. The liberal answer is to respect people as individuals, regardless of the genetic hand that they have been dealt. Genetic knowledge, however awkward, does not change that.

Kyle Munkittrick: From Gears to Genes: A Sea Change in Transhumanism

Kyle Munkittrick has penned a nice little retraction to Mark Gubrud's suggestion that transhumanism won’t work because mind uploading is impossible:

Only in the past decade have we started to realize that transhumanism won’t realize its dreams through mechanization and computerization. Though seminal authors on transhumanism, like Kurzweil, Moravec, Drexler, and More focus on nanotechnology and cybernetics, those technologies haven’t seen real progress since the 70’s.

But genetics and biotech has. Starting in the 1950’s with the Pill, vaccines, and antibiotics, our knowledge of medicine and biology radically improved throughout the second half of the twentieth century with assisted reproduction technologies like IVF, not to mention genomic sequencing, stem cell research, organ transplantation, and neural mapping, advances in biology and medicine are what are driving the transhumanist revolution. When someone like Mark Gubrud starts arguing transhumanism won’t work because we can’t upload our minds into robot bodies, one has to gawk for a moment in awe at the irrelevance of the argument. It’s like arguing we can’t ever cure cancer because cold fusion is impossible.

Transhumanism is the idea of guiding and improving human evolution with intention through the use of technologies and culture. If those technologies are not robotic and cybernetic but, instead, genetic and organic, then so be it. And that seems to be the way things are going.

Totally agree. I've also argued that uploading may not be possible, but that it's not a deal-breaker in our quest to live 'outside' our bodies.

Sato: Are We Close to Creating Super-Humans?

There's a good transhumanist-themed article by Rebecca Sato at The Daily Galaxy (which I highly recommend). Sato wonders if it would be so bad to use genetics to create enhanced humans:

What if a relatively simple procedure could make an individual and his or her offspring more compassionate, intelligent and thoughtful? Currently scientists are using gene therapy in an attempt to wipe out disease, but what if we could save many more lives by wiping out war instead though engineering humans to be less bloodthirsty, hateful and narrow-minded?

After all, Nature isn’t always right. Nature has naturally selected many people to carry the burden of uncomfortable and often lethal genetic disorders. If nature knows best, then shouldn’t we quit trying to “improve” upon nature by “curing” people of genetic conditions we consider inferior? Many say we shouldn’t change human genetics, UNLESS it’s the RIGHT thing to do. Who gets to decide where the line is between righteous endeavor and the corruption of nature? These are the questions facing our generation.

Read the entire article.

23andme.com

"...a web-based service that helps you read and understand your DNA. After providing a saliva sample using an at-home kit, you can use our interactive tools to shed new light on your distant ancestors, your close family and most of all, yourself."

Commentary:

• My Genome, Myself: Seeking Clues in DNA, New York Times, November 2007
• 23andMe Will Decode Your DNA for $1000. Welcome to the Age of Genomics, Wired Magazine, November 2007
• Welcome to the Future, Portfolio, November 2007
• The Buffett Mystery, Fortune, May 2007
• Are Home Genome Tests a Step Away from Eugenics?, Alternet (Annalee Newitz), December 2007
  

Just say no to mind controlling parasites

Genomes can be nasty. All they care about is self-replication, an agenda that often leads to some very strange and not-so-nice reproductive strategies. Genes are truly selfish.

Take mind controlling parasites, for example. These are viruses and simple organisms that have evolved such that they can alter the behavior of their hosts. Essentially, they cognitively re-engineer their victims, turning them into their transmission vectors. It is not uncommon for organisms to leech off several different species in this way as part of their reproductive cycle.

For example, there is Plasmodium gallinaceum, more commonly known as malaria. It's been known for some time that this virus protozoan uses mosquitoes as its vector. What has not been known until recently, however, is how malaria alters the blood sucking behavior of mosquitoes. Malaria has had a significant impact on the evolution of mosquitoes and their behavior, much like flowers have contributed to the evolution of its pollinators, namely bees and other flying insects.

Specifically, a mosquito will continue to search for victims until it reaches a threshold volume of blood. When it hits this threshold point, it stops host-seeking. It is thought that the stage-specific effect of the malaria parasite on host-seeking behavior is likely to be an active manipulation to increase its transmission success.

Then there's Dicrocoelium dendriticum. It's a virus that primarily infects sheep -- but it has a rather convoluted way of going about its reproductive business. First, adult worms lay eggs in the bile ducts of the sheep and are excreted. These eggs are in turn ingested by various species of land snails and the eggs hatch in their digestive tracts. This hatching releases a compound that continues to change until it is released by the snail in the form of a slimeball. This slimeball is then eaten by ants. This eventually develops into metacercariae within the abdominal cavity of the ants.

And here's where it gets interesting (not that it hasn't been a riveting tale to this point): the ant's behavior is in turn altered such that it is compelled to climb to the very top of a blade of grass where it waits to get eaten by sheep. The sheep eats the grass with the ant on it and subsequently becomes infected. The cycle is complete.

Similarly, Euhaplorchis californiensis causes fish to shimmy and jump so wading birds will grab them and eat them for the same reason.

Hairworms, which live inside grasshoppers, eventually need to leave their hosts to continue their life cycle. Rather than leave peacefully, however, they release a cocktail of chemicals that makes the grasshoppers commit suicide by leaping into water. The hairworms then swim away from their drowning hosts. Nice, eh?

Think humans are immune to mind controlling parasites? Think again. It is suspected that Toxoplasma gondii, a parasite that is often contracted by humans from their cats, affects human psychology. Normally the parasite works to manipulate rodents, but some scientists speculate that human cognition can also be altered.

Jaroslav Flegr, a parasitologist at Charles University in Prague, administered psychological questionnaires to people infected with Toxoplasma. He discovered that those who are infected show a small tendency to be more self-reproaching and insecure. Strangely, infected women tend to be more outgoing and warmhearted, while infected men tend to be more jealous and suspicious. Flegr has also shown that Toxoplasma may have an effect on human sex ratios -- to the tune of 260 boys for every 100 girls! (As an aside, it's worth noting that Flegr's research has been rejected by 8 journals, usually without formal review). Less controversial are studies that have shown links between Toxoplasma and schizophrenia.

This brings to mind a number of issues (no pun intended), including the freewill problem and the disturbing ease at which a virus can impact on something as important as an agent's behavior. The prospect exists for a deliberately engineered virus that can direct human psychology and decision making. The degree to which a virus could control behavior is an open question, but I'm inclined to think it's fairly limited. There's only so much you can do with germs, and simple organisms seem to be the most manipulable. Nano is a different story altogether, though.

Of course, there are other self-replicating entities that control human psychology much more profoundly than any mind control virus could. I'm thinking, of course, of memes. Cults, most notably Scientology, thrive on manipulating people with memetic techniques. Religions work in a similar manner but the degree to which a person is impacted varies from religion to religion. Propaganda is yet another way in which people's behavior can be modified.

Cults, religions and propaganda aside, a significant portion of human behavior is dictated by memetic influences. You can't escape the memepool; all our thinking is guided in part by the memes we carry. Our individual psychologies are molded by three basic influences: the memes we are exposed to, our genetic predispositions, and how we've been socially conditioned. This is a dynamic process that changes over time. It's my feeling that memes take up the largest chunk of this pie in terms of impact.

Oh, and apparently there's a fourth influence: Toxoplasma gondii. Just keep this in mind the next time you have to clean up your cat's poop.