One Wealthy Friend Would Make a 20 Year Difference

Healthy Life Extension

Funding Aging Research

One Wealthy Friend Would Make a 20 Year Difference

posted on May 22nd, 2012

Dear Future Centenarian,

Reason recently asked: œWhy are there no wealthy zealots?

Think about this: $25 million invested into a for-profit longevity venture fund the first year and about $100 million after that could launch us to a tipping point to reverse aging.

Outstanding success for the SENS Foundation and its mission would look something like the assured availability of $100-300 million for research and development. That much money tends to build the successes needed to attract more of the same.

To get to these points from where the fund and SENS Foundation stand now (a yearly budget around $1 million for the SENS Foundation and a start-up for the fund) might take twenty years of steady growth and success, with the end result being a substantial persuasion and conversion of the present research and funding culture for medical development.

It would give rise to a diverse and competitive community that inherits the founders' values and goals - to defeat aging.

So what happens if a person with a net worth of $200-400 million becomes a zealot for the cause, overnight perhaps, and decides to put his or hers net worth behind the cause? Because without life and health, what is money?

I use the world zealot in the best possible way here: someone who values the cause greatly enough to spend more time and money than most other people consider reasonable. But in this case it™s entirely justified, given the present harms caused by aging. (Of course, most multi-billionaires would barely notice the difference in their net worth and zero difference in their lifestyle.)

But what happens if the community acquires such a zealot? To my eyes, it looks like we would gain two decades of headway, and projects that would otherwise languish for twenty years and cost another quarter of a billion lives would commence immediately. In a pattern of growth that is limited only by the level of investment, which is exactly where rejuvenation biotechnology is today, everything in the timing hinges on when the money arrives.

The interesting question is why this doesn't happen. There are lots of very wealthy people in the world, and logic suggests that the best possible use for much of those resources from their individual perspectives would to buy more life. We are now in an age when it™s possible to make a run at buying lots more life.

What is wealth to the sick or the dead when it comes right down to it? But I don't think that this is a "Why don't more people support engineered longevity?" sort of a question. My suspicion is that in general, most grand causes that people can feel very strongly about also lack wealthy zealots.

It seems to me that there™s little overlap between the small population of zealots for a cause, people willing to devote their working life and significant resources to a grand project, and the small population of very wealthy people, those with a net worth of $100 million and up.

We can speculate as to why this might be. The passion for the process that will make a person wealthy takes up much the same mental space as the passion for a cause. There are only so many hours in the day, and only so much attention that a person can give to any one project. So you™re unlikely to see a person who has (a) accomplished the necessary devotion to work and process for a shot at becoming very wealthy, but also (b) put in the necessary work and process to become a zealot.

Or to put it yet another way, neither becoming exceedingly wealthy nor becoming a zealot are things that just happen one day out of the blue. They are each a fair way down their own different paths of effort, realization and specialization.

More Life,
David Kekich

P.S. Thanks to all who voted for œThe War on Aging in the poll last week. It won by a large margin, so thanks again.


It is taken as a tenet around here that involuntary death is a bad thing, and the process of getting to be dead despite your own wishes on the matter is arguably worse - it involves a great deal of ongoing suffering and pain as the body progressively fails. Greatly diminishing the incidence of death is one aim of the longevity science movement, achieved through the elimination of degenerative aging, the greatest cause of death. Can we say why being dead is bad, however?

That is supposedly a harder job than declaring suffering to be bad and worthy of amelioration - though most philosophers fail to consider the economic costs of destruction, and in the end it should all come down to "I've decided I don't like it, and so I'll work towards doing something about it through progress in medical science." Reasons beyond personal choice are unnecessary, but here is a brief tour of some of the philosophy of death and nonexistence:

"We all believe that death is bad. But why is death bad? In thinking about this question, I am simply going to assume that the death of my body is the end of my existence as a person. But if death is my end, how can it be bad for me to die? After all, once I'm dead, I don't exist. If I don't exist, how can being dead be bad for me? There's a puzzle raised by the Roman philosopher Lucretius, who thought it a mistake to find the prospect of my death upsetting.

Yes, as the deprivation account points out, after death we can't enjoy life's pleasures. But wait a minute, says Lucretius. The time after I die isn't the only period during which I won't exist. What about the period before my birth? If nonexistence is so bad, shouldn't I be upset by the eternity of nonexistence before I was born? But that's silly, right? Nobody is upset about that. So, he concludes, it doesn't make any sense to be upset about the eternity of nonexistence after you die, either.

It isn't clear how best to reply to Lucretius. One option, presumably, is to agree that we really do need to treat those two eternities of nonexistence on a par, but to insist that our prebirth nonexistence was worse than we thought. Alternatively, we might insist that there's an asymmetry that explains why we should care about the one period but not the other. But what is that difference? Perhaps this: When I die, I have lost my life. In contrast, during the eternity before my birth, although I'm not alive, I have not lost anything. You can't lose what you never had. So what's worse about death is the loss."

Researchers continue to investigate why the ApoE4 gene variant is associated with Alzheimer's disease: "A well-known genetic risk factor for Alzheimer's disease triggers a cascade of signaling that ultimately results in leaky blood vessels in the brain, allowing toxic substances to pour into brain tissue in large amounts, scientists report. A gene called ApoE4 makes people more prone to developing Alzheimer's.

People who carry two copies of the gene have roughly eight to 10 times the risk of getting Alzheimer's disease than people who do not. [Scientists] found that ApoE4 works through cyclophilin A, a well-known bad actor in the cardiovascular system, causing inflammation in atherosclerosis and other conditions. The team found that cyclophilin A opens the gates to the brain assault seen in Alzheimer's.

In the presence of ApoE4, increased cyclophilin A causes a breakdown of the cells lining the blood vessels in Alzheimer's disease in the same way it does in cardiovascular disease or abdominal aneurysm. In studies of mice, the team found that mice carrying the ApoE4 gene had five times as much cyclophilin A compared to other mice in cells known as pericytes, which are crucial to maintaining the integrity of the blood-brain barrier.

Blood vessels died, blood did not flow as completely through the brain as it did in other mice, and harmful substances like thrombin, fibrin, and hemosiderin, entered the brain tissue. When the team blocked the action of cyclophilin A, either by knocking out its gene or by using the drug cyclosporine A to inhibit it, the damage in the mice was reversed. Blood flow resumed to normal, and unhealthy leakage of toxic substances from the blood vessels into the brain was slashed by 80 percent."

Researchers here analyze the proteome of the hypothalamus and argue for an important role in coordinating bodily responses to ongoing changes caused by aging: "The aging process affects every tissue in the body and represents one of the most complicated and highly integrated inevitable physiological entities.

The maintenance of good health during the aging process likely relies upon the coherent regulation of hormonal and neuronal communication between the central nervous system and the periphery. Evidence has demonstrated that the optimal regulation of energy usage in both these systems facilitates healthy aging. However, the proteomic effects of aging in regions of the brain vital for integrating energy balance and neuronal activity are not well understood.

The hypothalamus is one of the main structures in the body responsible for sustaining an efficient interaction between energy balance and neurological activity. Therefore, a greater understanding of the effects of aging in the hypothalamus may reveal important aspects of overall organismal aging and may potentially reveal the most crucial protein factors supporting this vital signaling integration. In this study, we examined alterations in protein expression in the hypothalami of young, middle-aged, and old rats.

Based upon our rigorous analyses, we show that endogenous physiological responses to aging may be strongly orchestrated by the expression level of the GIT2 protein. The relevance of the hypothalamic expression level of this protein to the aging process in both neuronal and energy-controlling tissues reinforces the importance of this organ in the potential future development of targeted pharmacotherapeutics designed to interdict a multitude of age-related disorders."

A possible method of boosting muscle repair, and thus treating muscle wasting conditions - such as the sarcopenia that attends aging: "a lipid signaling molecule called sphingosine-1-phosphate or 'S1P' can trigger an inflammatory response that stimulates the muscle stem cells to proliferate and assist in muscle repair. Mdx mice, which have a disease similar to Duchenne Muscular Dystrophy, exhibit a deficiency of S1P, [and] boosting their S1P levels improves muscle regeneration.

The ability of muscles to regenerate themselves is attributed to the presence of a form of adult stem cells called 'satellite cells' that are essential for muscle repair. Normally, satellite cells lie quietly at the periphery of the muscle fiber and do not grow, move or become activated. However, after muscle injury, these stem cells 'wake up' through unclear mechanisms and fuse with the injured muscle, stimulating a complicated process that results in the rebuilding of a healthy muscle fiber.

S1P is a lipid signaling molecule that controls the movement and proliferation of many human cell types. S1P is able to 'wake up' the stem cells at the time of injury. It involves the ability of S1P to activate S1P receptor 2, one of its five cell surface receptors, leading to downstream activation of an inflammatory pathway controlled by a transcription factor called STAT3. [This results] in changes in gene expression that cause the satellite cell to leave its 'sleeping' state and start to proliferate and assist in muscle repair.

f these findings are also found to be true in humans with Duchenne Muscular Dystrophy, it may be possible to use similar approaches to boost S1P levels in order to improve satellite cell function and muscle regeneration in patients with the disease. Drugs that block S1P metabolism and boost S1P levels are now being tested for the treatment of other human diseases including rheumatoid arthritis. If these studies prove to be relevant in Duchenne patients, it may be possible to use the same drugs to improve muscle regeneration in these patients. Alternatively, new agents that can specifically activate S1P receptor 2 could also be beneficial in recruiting satellite cells and improving muscle regeneration in muscular dystrophy and potentially other diseases of muscle."

The media and public at large have been trained to think of medicine, and especially longevity-related medicine, in terms of pills - things you can consume, colorful drug capsules produced in the old-style fashion by Big Pharma. This is somewhat ridiculous, and leads to a focus on the entirely the wrong branches of research, those unlikely to deliver meaningful healthy life extension.

The future of rejuvenation biotechnology involves gene therapies, infusions of bacterial enzymes, and so forth; for the foreseeable future little of that will be stuff that you stick into your mouth. Calling these medicines drugs rather than procedures cheapens the complexity of what is being designed and developed. Nonetheless, the oral fixation in regard to public perceptions of medicine continues, fed by the lazy press and the self-interested supplement industry.

Here is an example of that sort of headlining: "But imagine if there were a drug that would slow down the aging process itself, a drug that didn't just treat a single disease but instead targeted multiple diseases of old age at once? It may sound far-fetched, but that's precisely what longevity scientists are working hard to produce. It's not just that we're trying to make people live longer; we're trying to make people live healthier. This is an exciting time for research.

Indeed, top-notch research labs are rolling out studies at a rapid rate, and a growing chorus of experts believe the advances being made will ultimately lead to a crop of drugs capable of extending healthy lifespans. Signs of progress are abundant in medical journals. [researchers] published results showing they could markedly delay the onset of age-related diseases in mice by killing off the rodents' senescent cells.

Senescent cells have stopped dividing and accumulate as organisms age. Though seemingly dormant, they're not: Just as old cars in junkyards can leak oil for years, they emit harmful substances that appear to fuel many of the diseases that strike older people. And it's not just senescence research that is stoking excitement. Another team of scientists [has] managed to control the aging process by targeting specialized structures at the tips of chromosomes called telomeres. Other scientists have found that feeding aging mice rapamycin - an immunosuppressant that's used to prevent organ rejection after transplants - can extend the lifespan of mice significantly."

Researches make an incremental step forward in understanding the root causes of rheumatoid arthritis: "Untangling the root cause of rheumatoid arthritis has been a difficult task for immunologists, as decades of research has pointed to multiple culprits in our immune system, with contradictory lines of evidence.

Now, [researchers] announce that it takes a diverse array of regulatory T cells (a specialized subset of white blood cells) to prevent the immune system from generating the tissue-specific inflammation that is a hallmark of the disease. Regulatory T cell diversity, the researchers say, provides a cumulative protective effect against rheumatoid arthritis.
Regulatory T cells (or Tregs) are a necessary component to either restrain (or encourage) the immune system's inflammatory response.

Tregs are activated as molecules on their surface membranes called T cell receptors interact with 'friendly' or 'self' molecules - a way for the immune system to recognize friend from foe. Mismanagement of these Tregs, which normally serve to restrain the immune system from over-reacting to healthy tissue, could then lead to runaway inflammation. In this study, the researchers sought to examine how T cell receptors affect the ability of Tregs to suppress arthritis in a mouse that had been bred to express a 'self' molecule that drives arthritis.

They showed that an array of Tregs given to the mice effectively stops arthritis. Unexpectedly, however, Tregs that are specific for the surrogate 'self' molecule do not prevent arthritis. We find that [a] diverse repertoire of Tregs are very effective. All of these Tregs, together, influence other components of the immune system which serves to slow down the inflammatory process that causes RA."

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