Longevity Meme Newsletter, July 12 2010

July 12 2010

The Longevity Meme Newsletter is a weekly email containing news, opinions, and happenings for people interested in aging science and engineered longevity: making use of diet, lifestyle choices, technology, and proven medical advances to live healthy, longer lives. This newsletter is published under the Creative Commons Attribution 3.0 license. In short, this means that you are encouraged to republish and rewrite it in any way you see fit, the only requirements being that you provide attribution and a link to the Longevity Meme.



- Immunosenescence and What to Do About It
- On Death as Oblivion
- Cryonics and Spousal Objections
- Discussion
- Latest Healthy Life Extension Headlines


Immunosenescence is the steady decay of the immune system with advancing age. It stops doing its job, and that loss is a fair part of the frailty suffered now by old people, and the frailty we will all suffer in the future unless something is done:


"For the adaptive immune system at least, researchers have a good picture as to why and how this happens - which means that they also have starting points to develop ways to reverse immunosenescence. In essence, the immune system fails because the thymus, source of immune cells, ceases production and withers away. At the same time, the population of immune cells becomes ever more biased towards memory cells and away from cells capable of fighting new infections - and this is largely due to persistent viruses like cytomegalovirus. Eventually the immune system becomes so focused on the viruses it cannot clear from the body that it has no resources left to perform its other functions.

"These problems suggest their own solutions: replace or rejuvenate the thymus, for example, or apply new targeted cell-killing methods developed for cancer therapies to destroy unwanted memory cells. On that note it's worth recalling that thymus transplants have been shown to extend life in mice, but there is plenty of other evidence to support these and similar attempts to restore the aging immune system to youthful levels of activity."



No-one really likes to put much thought into death, especially their own. That fact is one of the obstacles that stands in the way of a broader discussion of ways to defeat age-related degeneration and extend the healthy human life span. Thus attitudes towards death are an important consideration in advocacy for engineered longevity:


"Insofar as death is oblivion, the destruction of the self, it is rational to be unconcerned about being dead. You won't exist to have feelings on the matter - which is exactly the same situation as for all time prior to the point in your development at which you like to think that you became yourself.

"Equally, it is rational to be very concerned about being dead at some point in the future. Humans are creatures of action. We like to achieve, observe, and experience. We place value upon these things, and death will stop us from gathering that value.

"So the world of people might be divided at any point in time into (a) the group that is horrified by the prospect of oblivion, and (b) the group that is unbothered by personal extinction. It's a very sharp dividing line, not often explored in casual conversation, for all that one person's views might cross back and forth between camps over the years. Try a poll of the folk you know at some point in time: I think you'll find the results interesting."

"There is a school of thought that suggests selling the concepts of radical life extension as indefinite postponement of death is inefficient. In this view, half the people the world don't really care about the future state of being dead; what they care about is the prospect of pain, injury, and degeneration. Therefore the better pitch for engineered longevity focuses on elimination of the pain and degeneration of aging, and the continuation of youthful health for as long as a person desires."


A sadly common situation in the cryonics community is for a spouse to vigorously object to their partner signing up for cryopreservation. Cryonics is, as you might recall, the process of low-temperature storage at clinical death, with the aim of preserving the fine structure of the brain for future restoration. It is, at present, the only chance of a greatly extended life span for those people who will die before the advent of rejuvenation therapies. But why the spousal hostility? This phenomenon was recently examined in the New York Times, of all places:


"In cryonics circles, it is not unusual to hear tales of a spouse - usually a wife, as most people presently signed up for cryopreservation at clinical death are male - who is adamantly opposed to cryonics, even to the point of requiring the potential cryonics patient make a choice between cryonics or the partner. This has always struck me as odd, but it is clearly more than just an urban myth or a few anecdotal couples; there is some core incentive or common aspect of human psychology at work here that generates these conflicts often enough to make the situation well known. (Well known to cryonics supporters, at least).

"For my part, I'd say it seems unreasonable (to say the least) to expect your partner to commit suicide to make you feel better - and abstaining from cryopreservation on death is exactly a form of suicide. The practice of suttee, in which widows were compelled to die upon their late husband's funeral pyre, is now generally acknowledged as barbaric and murderous. But at the high level it is little different from brow-beating a partner into abandoning cryonics, or worse, actively working to ensure that a partner's cryonics arrangements go awry. Still, a great many people for a long period of years accepted suttee as good and proper - just as a great many people today accept all sorts of correctable malignancies in cultures and the human condition."

What is accepted is no guide to what is right.


The highlights and headlines from the past week follow below.

Remember - if you like this newsletter, the chances are that your friends will find it useful too. Forward it on, or post a copy to your favorite online communities. Encourage the people you know to pitch in and make a difference to the future of health and longevity!




The Alcor executive director's reports provide a good window into the day to day operations of a cryonics provider - which is as much a community as it is a business. For example: "In mid-May, we cryopreserved 92-year-old Paul Garfield, a neuropreservation patient. Paul was a dedicated member of Alcor for 20 years and a long-time volunteer at the organization. Even in his 90's Paul maintained an active lifestyle, often going dancing and visiting Alcor weekly. After being hospitalized in early 2009, he moved out of state to live with relatives. Alcor developed a cordial relationship with his son, who expressed a desire to honor his father's wish for cryopreservation, despite personal reservations. The son informed Alcor in March that Paul had suffered a stroke and was undergoing physical therapy. On May 11, Paul was admitted to hospice care after his condition deteriorated, possibly due to another stroke. Alcor immediately deployed Aaron Drake and Suspended Animation to perform a standby that ultimately lasted about a day. Several Alcor Texas team members also offered assistance gathering supplies, providing transportation, and participating in the standby. Following pronouncement, Suspended Animation immediately began stabilization procedures and performed a successful field washout. He arrived in Alcor's operating room approximately 20 hours post-pronouncement, and we achieved terminal perfusion. Paul became Alcor's 95th patient."

Via EurekAlert: "Scientists have discovered a compound that restores the capacity to form new memories in aging rats, likely by improving the survival of newborn neurons in the brain's memory hub. ... This neuroprotective compound, called P7C3, holds special promise because of its medication-friendly properties. It can be taken orally, crosses the blood-brain barrier with long-lasting effects, and is safely tolerated by mice during many stages of development. ... Physical activity, social, or other enriching experiences promote neurogenesis – the birth and maturation of new neurons. This growth takes place in the dentate gyrus, a key area of the brain's memory hub, the hippocampus. But even in the normal adult brain, most of these newborn neurons die during the month it takes to develop and get wired into brain circuitry. To survive, the cells must run a gauntlet of challenges. Newborn hippocampus neurons fare much worse in aging-related disorders like Alzheimer's, marked by runaway cell death. In hopes of finding compounds that might protect such vulnerable neurons during this process, [researchers] tested more than 1000 small molecules in living mice. ... To find out if P7C3 could similarly stem aging-associated neuronal death and cognitive decline, the researchers gave the compound to aged rats. Rodents treated with P7C3 for two months significantly outperformed their placebo-treated peers on a water maze task, a standard assay of hippocampus-dependent learning. This was traced to a threefold higher-than-normal level of newborn neurons in the dentate gyrus of the treated animals."

News of a study linking telomere length and cancer risk, but it's still the case that the relationship could be indirect, such as both sides of the correlation being based on levels of biochemical damage. For example, it might reflect the state of mitochondrial biochemistry in a person: "A new study suggests that shorter length of leukocyte telomeres - chromosome markers of biological aging - are associated with an increased risk of cancer and death from cancer. ... Telomeres are a structure at the end of a chromosome involved in the replication and stability of the chromosome. Genetic factors and environmental stressors can shorten the length of the telomere, and telomere length has been considered to be an emerging marker of biological age. Some research has suggested that short telomeres and chromosomal instability contribute to malignant cell transformation. ... [Researchers] conducted a study to assess the association between leukocyte telomere length and risk of both new-onset cancer and cancer death. Leukocyte telomere length was [measured] in 787 participants, free of cancer in 1995 ... Analysis indicated that short telomere length at the beginning of the study was associated with new cancer independently of standard cancer risk factors. Compared with participants in the longest telomere length group, participants in the middle length group had about twice the risk of cancer, and those in the shortest length group had approximately three times the risk. Cancer incidence rates were inversely related to telomere length, with participants in the group with the shortest telomere length having the highest rate of cancer."

Much like the slow and steady lengthening of life expectancy, there is a general improvement in cancer treatment outcomes thanks to progress across the board in modern medicine: "The continued drop in overall cancer mortality rates over the last 20 years has averted more than three-quarters of a million (767,000) cancer deaths according to a new report from the American Cancer Society. The American Cancer Society's annual Cancer Statistics article reports that the overall death rate from cancer in the United States in 2007 was 178.4 per 100,000, a relative decrease of 1.3 percent from 2006, when the rate was 180.7 per 100,000, continuing a trend that began in 1991 for men and 1992 for women. In that time, mortality rates have decreased by 21 percent among men and by 12 percent among women, due primarily to declines in smoking, better treatments, and earlier detection of cancer. ... Cancer incidence rates decreased in men 1.3 percent per year from 2000 to 2006 and in women 0.5 percent per year from 1998 to 2006. Death rates for all cancer sites combined decreased 2 percent per year from 2001 to 2006 in males and 1.5 percent per year from 2002 to 2006 in females."

ON MITOHORMESIS (July 07 2010)
A little stress improves our biochemistry: "Recent evidence suggests that calorie restriction and specifically reduced glucose metabolism induces mitochondrial metabolism to extend life span in various model organisms, including Saccharomyces cerevisiae, Drosophila melanogaster, Caenorhabditis elegans and possibly mice. In conflict with Harman's free radical theory of aging (FRTA), these effects may be due to increased formation of reactive oxygen species (ROS) within the mitochondria causing an adaptive response that culminates in subsequently increased stress resistance assumed to ultimately cause a long-term reduction of oxidative stress. This type of retrograde response has been named mitochondrial hormesis or mitohormesis, and may in addition be applicable to the health-promoting effects of physical exercise in humans and, hypothetically, impaired insulin/IGF-1-signaling in model organisms. Consistently, abrogation of this mitochondrial ROS signal by antioxidants impairs the lifespan-extending and health-promoting capabilities of glucose restriction and physical exercise, respectively. In summary, the findings discussed in this review indicate that ROS are essential signaling molecules which are required to promote health and longevity. Hence, the concept of mitohormesis provides a common mechanistic denominator for the physiological effects of physical exercise, reduced calorie uptake, glucose restriction, and possibly beyond."

Russian cryonics provider KrioRus is starting to receive the sort of mixed press attention that Alcor did five years ago or so: "'I don't ever want to die... It wouldn't suit me,' said Innokenty Osadchy. Fortunately, the 35-year-old investment banker is certain he has found a loophole out of death. Osadchy is ready to pay a small fortune to freeze his brain until future technology allows him to continue his life - after being transplanted into a new body and resuscitated. 'Why do I have to die in a couple decades? I don't see any logic in this. It won't be another life, it'll be the continuation of my life. I don't ever want to die ever. Not in a year, not in a million years.' Osadchy and other clients of Russian cryonics company KrioRus believe the brain operates like a computer hard-drive and its contents can be frozen and stored for the future. 'We know that the personality is stored in the brain. So when a person's body is old, there's no reason to keep it,' said Danila Medvedev, who runs KrioRus, the first cryonics outfit outside the United States. ... Since its 2005 launch, KrioRus has been building new vats, in anticipation of the 30 clients, like Osadchy, with whom it already has contracts."

This paper suggests that the relationship between mitochondrial DNA variants and longevity is complex: "There is substantial evidence that mitochondria are involved in the aging process. Mitochondrial function requires the coordinated expression of hundreds of nuclear genes and a few dozen mitochondrial genes, many of which have been associated with either extended or shortened life span. Impaired mitochondrial function resulting from mtDNA and nuclear DNA variation is likely to contribute to an imbalance in cellular energy homeostasis, increased vulnerability to oxidative stress, and an increased rate of cellular senescence and aging. The complex genetic architecture of mitochondria suggests that there may be an equally complex set of gene interactions (epistases) involving genetic variation in the nuclear and mitochondrial genomes. Results from Drosophila suggest that the effects of mtDNA haplotypes on longevity vary among different nuclear allelic backgrounds, which could account for the inconsistent associations that have been observed between mitochondrial DNA (mtDNA) haplogroups and survival in humans. ... We hypothesize that aging and longevity, as complex traits having a significant genetic component, are likely to be controlled by nuclear gene variants interacting with both inherited and somatic mtDNA variability."

This post at Less Wrong makes the case for cryonics as a business that would work well at large scale: "Cryonics scales very well. People who argue from the perspective that cryonics is costly are probably not aware of this fact. Even assuming you needed to come up with the lump sum all at once rather than steadily pay into life insurance, the fact is that most people would be able to afford it if most people wanted it. There are some basic physical reasons why this is the case. ... Surface area is where heat gains entry. Thus if you have a huge container holding cryogenic goods (humans in this case) it costs less per unit volume (human) than is the case with a smaller container that is equally well insulated. ... liquid nitrogen, the super-cheap coolant used by cryonics facilities around the world, is vastly cheaper (more than a factor of 10) when purchased in huge quantities of several tons. The scaling factors for storage tanks and high-capacity tanker trucks are a big part of the reason for this. ... The conclusion I get from this is that there is a very strong self-interested case (as well as the altruistic case) to be made for the promotion of megascale cryonics towards the mainstream, as opposed to small independently run units for a few of us die-hard futurists."

There's nothing you can do right now that will have a greater immediate effect on your life expectancy than exercise and calorie restriction. The best thing you can do for future improvement is to help researchers raise funds to develop repair technologies for human aging. But no-one wants to hear that. Everyone wants a silver bullet now, and it doesn't exist: "Friends occasionally ask me how they might best live healthy, longer. They inquire because I went to medical school, work in biotech, and focus professionally on developing drugs to treat diseases of aging by targeting aging genes. My response seems to surprise them, because it does not center on pharmaceutical products. The current answer on how to increase healthy human lifespan is simple: 'Eat less, and exercise more.' ... Modern medicine has discovered an impressive number of lifesaving new drugs for devastating diseases such as cancer, diabetes, heart disease, and infectious diseases. Nevertheless, for most of us, active lifestyles and less food will have a more profound effect than taking more medicines. Hard as it is, we should walk, run, and bike more, and reduce our food intake. The best way we can increase our chances to live healthy, longer is simple: eat less and exercise more."

A response to recent discussion of the Catholic hierarchy's views on engineered longevity: "Michael Anissimov and Aubrey de Grey call our attention to Pope Benedict's Holy Saturday address from 3 April of this year. In the address, the Pope presents perspective on immortalism, suggesting that radical extension of life as we currently know it is not a cure for death, but rather a cure for death must 'transform our lives from within' and 'create a new life within us, truly fit for eternity'. The Pope's message contains some ideas with which I disagree. For example, he questions the value of extending life hundreds of years and suggests it would be condemnation; does he consider us already condemned as a consequence of extending life well beyond the few decades that were available to our ancestors? Perhaps he does, as do many Catholics, embracing a doctrine of original sin and assuming life as we now know it to have no possibility of naturally improving beyond the consequences of that original sin. He reasons that immortalism would leave no room for youth, yet youth is precisely the goal of immortalism - not merely a perpetuation of geriatric hacks. He also reasons that immortalism would kill capacity for innovation, yet capacity for innovation has only improved as we've extended our lifespans. Finally, he implies that death itself is where we should look to find the beginning of the fullness of life. While I don't consider death the absolute end of identity, I consider it to be among the worst of hollow and meaningless contradictions to equate death with life."



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