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Chris Patil at Ouroboros has dropped two sets of recent research into our laps for consideration, with a focus on continuing efforts to understand the intricacies of human biochemistry as it relates to longevity and aging.

• Keeping up with IGF-I and FOXO
• No end to telomeres

I find most of the work on insulin metabolism and insulin-like growth factor-1 (IGF-1) somewhat heavy going. It's very much down in the depths of metabolic mechanisms, for all that it's related to straightforward demonstrations of single gene longevity mutations in lower animals. It's somewhat analogous to work on calorie restriction mechanisms - in that it draws together energy from food and longevity to a mysterious biochemical middle - but perhaps more opaque because practical applications aren't as advanced at this stage.

Telomeres are more intuitive, however:

Telomeres - the structures at the end of chromosomes - have a long history in biogerontology. Telomeres shorten with every cell division, essentially providing a 'clock' that ticks down until reaching some critical length, at which point the cell will undergo the permanent growth arrest known as senescence. Even though this clock is an important tumor suppression checkpoint (because it prevents cells that have divided many times from continuing to proliferate), senescent cells themselves contribute both directly and indirectly to aging (by diminishing regenerative capacity and secreting deleterious signaling molecules, respectively). Telomere length is also a useful biomarker: it is positively correlated with life expectancy, and appears to respond to environmental influences including chronic infection and psychological stress.

One item of note in the list is that telomerase appears to have other roles beyond lengthening telomeres:

recent studies have led some investigators to suggest novel biochemical properties of telomerase in several essential cell signaling pathways without apparent involvement of its well established function in telomere maintenance. … This review will provide an update on the extracurricular activities of telomerase in apoptosis, DNA repair, stem cell function, and in the regulation of gene expression.

This is important for those groups working on telomerase-based therapies, and has implications for the viability of the proposed WILT strategy that would disable telomerase in order to eliminate cancer. As always, it's a challenge to interfere precisely in human biochemistry when every component has multiple important functions.

Molecular biologist Attila Chordash recently conducted a short interview with Dave Gobel, co-founder of the Methuselah Foundation. He's been determinedly working away to make this thing a success since the beginning. You can find the interview over at Pimm. His thoughts on the Mprize for longevity research caught my eye:

You put up the money and tell competitors what they need to do. The larger the prize, the more competitors. It's like an inexpensive way of being able to put chips on every single spot on a roulette table. The best way to find a solution to unknown problems is to generate high motivation among the greatest number of thinkers/actors without too much regard to reputation of the competitors - let the best outcome win - I don’t care how they dress.

Incentives make the world go round, which is why research prizes are so effective. The prospect of money and fame are wonderful motivators, as is demonstrated in the business community each and every day. It's a pity that this obvious truth is so often forgotten when it comes to the highly regulated field of medical research and development.

It's a shame that the people most harmed by the existence of the FDA - and the culture of "I have power over you and you shall do as I say" that supports it - are not up in arms. The most vocal opponents of the FDA over the past decade or so are probably folk in the supplement industry. They, despite the threat of jail, losses, and other indignities for doing no more than providing a desired and responsible commercial service, are by no means the most harmed. No, the most harmed are the dying, and we are all counted in that group while the FDA continues in its position that potential longevity therapies will not be approved. No approval means no funds for development, and hence little evidence to show in support of radical change.

The cancer patients, the Alzheimer's sufferers, and all those with other named medical conditions suffer as well: the FDA and associated regulatory bodies form a huge ball and chain that slows progress in science to a fraction of what it might be. When medical development costs much more due to regulation, you will see fewer new medicines. When government employees have greater incentive to deny than approve, you will see fewer new medicines. This is exactly what happens, and the cost is measured in lives.

Back to the supplement industry. One of their voices can be found at the Consumers Against High Drug Prices site, an earnest place that nonetheless seems to me to be missing the real point of the exercise. But it is a supplement industry effort, and that narrows their focus to bottles and herbs - the here and now, rather than what could be, and what might have been in medical research. They would like to largely dismantle the FDA in their neck of the woods - but that sort of renegotiation of the contract with government employees never really works. When was the last time you recall government employees giving up the option to interfere in a given area of commerce? That option to interfere - and cause destruction and mayhem - is how politicians maintain their influence. It's the rule of the sword for a modern age.

You have to keep the incentives in mind. Politicians and government employees have no incentive to play nice and leave you be, no matter what the paper says. So they won't. Trying to redirect or reclassify the power held by others to your benefit is a form of self-delusion: once you're set on that course, the politicians already own your mind. It's a shell game, slightly more complicated and obscure than the voting shell game, but really no different in essence. The only solution to government abuse of power is the absence of that power.

Centralization of power - the state and regulation, in other words - is a form of age-related damage for human societies. It accumulates, piling ever deeper and broader, and leads to degeneration and disease. Look no further than the Soviet Union for an example of where it all leads in the end, but the place we are now is a far cry from the best of all worlds. If you have an interest in a long, healthy life, then you should also have an interest in why modern democracies are greatly slowing progress to that end.

Aetna, through its nonprofit foundation, is funding research to find out whether a daily lottery with cash prizes will help improve patients' medication adherence.

The Aetna Foundation last fall gave researchers a $400,000 grant to fund a study at the University of Pennsylvania that will use prizes of $10 and $100 as rewards for taking medication as prescribed.

"If it looks like it works, we'll try to incorporate it in things we do," said Aetna Chief Medical Officer Troyen A. Brennan, MD, MPH.

Kevin G. Volpp, MD, PhD, director of the Center on Health Incentives at the Leonard Davis Institute for Health Economics at the University of Pennsylvania's Wharton School, and Stephen E. Kimmel, MD, associate professor of medicine at the University of Pennsylvania School of Medicine, have designed a two-arm randomized trial with 100 participants to test a daily lottery as incentive for taking warfarin as prescribed.

An electronic monitor will track whether all participants are taking their medicine.

The 50 people enrolled in the lottery will have a 1-in-10 chance of winning $10 every day they take their medication and a 1-in-100 chance of winning $100. Each day a text message will tell a subject whether he or she has won the lottery, or, if the dose wasn't taken, whether he or she would have won, Dr. Volpp said.

The 50 people in the control group will use the same monitor but won't be entered in the lottery.

Aetna chose to sponsor the research because adherence is key to quality of care, Dr. Brennan said. He said statistics show that a year after beginning medication, only about 50% of patients are taking their medications as directed.

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The brain is a singular organ - our selves are defined by its structure. The aging brain can't be replaced by the same near-future tissue engineering techniques that will give us new hearts and other organs grown fresh from our own stem cells. Thus we are going to have to become very good at repairing the brain in situ, cell by cell, aggregate by aggregate.

One of the biotechnologies needed to achieve this goal is mature regenerative medicine, specifically the ability to manipulate and reprogram stem cells within the brain. Those stem cells must first be found and categorized, and progress continues on that front:

Evidence strongly shows that the true stem cells in the mammalian brain are the ependymal cells that line the ventricles in the brain and spinal cord, rather than cells in the subventricular zone as biologists previously believed. Brain ventricles are hollow chambers filled with fluid that supports brain tissue, and a layer of ependymal cells lines these ventricles.

Knowing the cell source is crucial when developing stem cell-based therapies. Additionally, knowing that these normally dormant cells can be coaxed into dividing lays the groundwork for future therapies in which a patient's own stem cells produce new brain cells to treat neurological disorders and injuries such as Parkinson's disease, stroke or traumatic brain injury.

"With such a therapy, we would know which cells in the body to target for activation, and their offspring would have all the properties necessary to replace damaged or missing cells," said Darius Gleason, lead author of the study and a graduate student in the Department of Developmental and Cell Biology. "It is a very promising approach to stem cell therapy."

Replacing cells is only one part of repairing an age-damaged brain, however. You might take a look at the Strategies for Engineered Negligible Senescence to see the many other issues that accumulate in brain tissue over the course of a lifetime. A lot of work lies ahead.