LONGEVITY MEME NEWSLETTER
December 27th 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.
- "Death is an inconvenient obstacle on the road to immortality"
- Small Steps Towards Exercise Mimetics
- News from the Cryonics Community
- Latest Headlines from Fight Aging!
"DEATH IS AN INCONVENIENT OBSTACLE ON THE ROAD TO IMMORTALITY"
But is pitching longevity science as the fight against death the right way to go? Some thoughts on that matter:
"The spirit in which this [quote] is intended is evidently that an army of biogerontologists and supporters should marshal, march, and trample death beneath their sandaled feet - to leave it broken in the dust upon the road that leads to rejuvenation biotechnology and agelessness. ... If you stop to think about this for a moment, however, you might conclude that the defeat of death should not in fact be the conceptual focus of efforts to extend the healthy human life span. Let's try an analogy here: 'The ground is an inconvenient obstacle on the road to flight.' Fail at flying, and a harsh encounter with the ground is your fate - in much the same way as death by aging is the fate that awaits us should we fail to achieve the technologies capable of repairing the biological damage of aging. Yet heavier than air flight wasn't achieved though a focus on the ground: the early aeronauts and their supporters didn't raise funding and convince the public of the viability of heavier than air flight through 'defeat the ground!' campaigns. Their eyes looked up, to the skies, to rapid travel across land and ocean, to daring acts and barnstorming.
"Returning to physical immortality - meaning the state of agelessness attained through biotechnology and diligent repair - then we might see that the grail here is life achieved, not death denied (or trampled). It is living, being healthy, able to plan ahead for decades without fear, to not be faced with inevitable pain, suffering, and frailty. These points are the focus."
SMALL STEPS TOWARDS EXERCISE MIMETICS
Exercise, like calorie restriction, produces measurable benefits in health and identifiable changes in our metabolism. Just as researchers have been working to mimic the effects of calorie restriction, so too are they working to produce exercise mimetic drugs:
"The driving idea here is that people will pay for medical technologies that provide some of the benefits of calorie restriction or exercise without the need for the hard work and willpower involved in the real thing. This seems like a reasonable conjecture, and so plenty of money is flowing into research and development for calorie restriction and exercise mimetic drugs. Where this research starts is the search for genes or proteins that can be manipulated to trigger some of the specific, measurable health or longevity benefits resulting from these lifestyle choices."
"By tweaking a single gene, scientists have mimicked in sedentary mice the heart-strengthening effects of two weeks of endurance training ... The genetic manipulation spurred the animals' heart muscle cells - called cardiomyocytes - to proliferate and grow larger by an amount comparable to normal mice that swam for up to three hours a day."
NEWS FROM THE CRYONICS COMMUNITY
This past week, I pointed out a fascinating historical analysis and retrospective of the development of cryonics as a community and industry:
"Cryonics, as you no doubt know by now, is the low-temperature storage of the recently deceased. The fine structure of the brain can be very well preserved - well enough that all the data that forms your self remains intact. Future medical technologies, such as applications of molecular nanotechnology, will eventually prove capable of repairing cryopreserved individuals and restoring them to life. A number of people have been cryopreserved and stored over the past few decades, and a modest community of cryobiology researchers, workers, advocates, and funding sources continues this work."
"My attention was recently directed to a series of presentations by Mike Darwin, which are in part an analysis of the failure of the cryonics community of past decades to blossom into a large industry, and in part a personal recollection of that history. If you want to understand more about the history of the cryonics movement, and how it came to be where it is today, you should certainly read this."
Following on from that, it seems that cryonics provider Alcor has hired what should be a familiar face as their new CEO:
"The Board of Directors of Alcor Life Extension Foundation today announced that Dr. Max More, 46, has been named Chief Executive Officer effective Jan 1, 2011. ... More might be considered one of the founding members of the modern transhumanist community, with a long running interest in engineering greater human longevity. He is the author of the Extropian Principles, amongst numerous other works, a vision of open societies working to transcend the limits of our evolved biology through research and development of new technologies."
As I've noted in the past, in order to provide cryonics services to a greater number of people, Alcor simply has to grow, become more professional, diversify their technologies into other profitable outlets - doing all the things that any business must do as it moves forward to greater success. I hope that this hire represents the beginning of greater progress towards those goals.
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!
LATEST HEADLINES FROM FIGHT AGING!
FOLLOWING THE BIOCHEMICAL PATHWAYS OF AGING, STEP BY STEP
Friday, December 24, 2010
The mainstream biogerontology community is engaged in the very, very long and complex process of unpicking all of the detailed changes in biological signaling pathways that occur with aging. The starting points are identified metabolic changes that accompany treatments, lifestyle choices, or environmental circumstances known to extend life. The end result is to fully understand why these low-level biochemical changes lead to longer life span, and replicate or better them. This is a very long term project, which is why many of these researchers do not expect meaningful artificial extension of human life span within their lifetimes, even allowing for accelerating growth in biotechnology and computing power. This article is an example of this sort of research: "researchers have linked hyperactivity in the [mammalian] target of rapamycin complex 1 (mTORC1) cellular pathway to reduced ketone production in the liver, which is a well-defined physiological trait of aging in mice. During sleep or other times of low carbohydrate intake, such as fasting or periods of dieting, the liver converts fatty acids to ketones, which are vital sources of energy during fasting, especially for the heart and brain. As animals age, their ability to produce ketones in response to fasting declines. ... This is the first time that the mTORC1 pathway has been shown to affect a trait associated with aging. This discovery will enable researchers to study the aging process in greater detail, helping them to determine how and why aging suppresses ketone production and activates mTORC1."
SUPPRESSING GROWTH HORMONE TO EXTEND LONGEVITY IN MICE
Friday, December 24, 2010
It should not be a surprise to see suppression of growth hormone in mammals result in extended healthy life spans. After all, the present record holder for the Mprize for mouse longevity involved gene engineering of a growth hormone deficient breed. Here researchers demonstrate benefits in a mouse breed used for Alzheimer's research, as it develops accelerated degeneration of the brain: "people sometimes take growth hormone, believing it will be the fountain of youth. ... Many older people have been taking growth hormone to rejuvenate themselves. These results strongly suggest that growth hormone, when given to middle aged and older people, may be hazardous. ... The scientists studied the compound MZ-5-156, a 'growth hormone-releasing hormone (GHRH) antagonist.' They conducted their research in the SAMP8 mouse model, a strain engineered for studies of the aging process. Overall, the researchers found that MZ-5-156 had positive effects on oxidative stress in the brain, improving cognition, telomerase activity (the actions of an enzyme which protects DNA material) and life span, while decreasing tumor activity. MZ-5-156, like many GHRH antagonists, inhibited several human cancers, including prostate, breast, brain and lung cancers. It also had positive effects on learning, and is linked to improvements in short-term memory. The antioxidant actions led to less oxidative stress, reversing cognitive impairment in the aging mouse."
PROFILING THE WORK OF THE DAVIS SCHOOL OF GERONTOLOGY
Thursday, December 23, 2010
Singularity Hub looks at the some of the work of mainstream gerontology: "Researchers are working diligently to address the seemingly unavoidable realities of aging and dying. In fact, the University of Southern California founded the Davis School of Gerontology for such a purpose, and the institute serves as the oldest and largest institute of its kind. .. Faculty at the Davis School of Gerontology have adopted a multi-pronged approach to the problem and are pursuing various avenues that may lead to a solution. Caleb "Tuck" Finch and his colleagues have been investigating the interaction between inflammation and the aging process. He posits that postnatal factors such as environmental pollution and diet may exert aging effects through inflammation pathways. He also investigates the role hormones may have on the aging process, observing how changes in sex hormones late in life could mediate neural senescence. Generally, he is optimistic about treating the neurodegenerative diseases of aging, believing we'll be able to lower the risk of Alzheimer's and control its course by the next decade ... Another faculty member, Dr. Valter Longo, extended the lifespan of yeast 10 times. If there were a yeast category for the Methuselah Foundation's Mprize (an award given to scientists who significantly increase the lifespan of mice), Dr. Longo would have won handily. In both yeast and mice, a surefire way to enhance longevity is through caloric restriction (CR), which is essentially a state of persistent hunger. On its own, CR can produce a 3-fold and 30-50% lifespan increase in yeast and mice, respectively. ... Dr. Longo has helped identify the downstream molecular targets of CR, so with appropriate drugs and genetic manipulation, food abstinence may not be necessary."
CAN LIPOFUSCIN BE MADE LESS HARMFUL?
Thursday, December 23, 2010
Lipofuscin is a mix of metabolic byproducts that the body cannot break down. It accumulates with age, and causes some important forms of cellular dysfunction that contribute to aging. Ideally researchers would be working on ways to periodically clear liposfuscin from the body, but here they are investigating how it might be made less damaging: "Lipofuscin, a highly oxidized aggregate consists of covalently cross-linked proteins, lipids and sugar-residues, and is one of the major lifespan-limiting factors in postmitotic aging cells. An artificial model of this material, showing characteristics and effects comparable to the natural form, has turned out to be very useful for in vitro studies. Artificial lipofuscin was used to investigate its effects on the viability of human fibroblasts, its rate of uptake and its ability to inhibit the proteasomal system. The inhibition of the proteasomal system is one of the major aspects of the cytotoxic effects of lipofuscin. We present here that this proteasomal inhibition is due to a proteasomal binding on the lipofuscin surface motifs, degradable by protease K. Furthermore, removal of surface peptide structures by protease K strongly reduces cytotoxic effects of lipofuscin and binding of cellular proteins and proteasome to intracellular protein aggregates." Achieving this end would still leave the lipofuscin stuck in the cell, bloating the lysosomes, however - breaking it down would be much better.
A HUMAN INTEREST NAKED MOLE RAT STORY
Wednesday, December 22, 2010
As you might know, the naked mole rat is of great interest to aging researchers: "For three decades, Old Man selflessly helped scientists unravel the mysteries behind Alzheimer's, osteoporosis, cancer and other age-related diseases. Born in Kenya, he lived an active life - including siring offspring - until early Thanksgiving, when his body was discovered in a lab at the Barshop Institute for Longevity and Aging Studies on the campus of the Texas Research Park. A naked mole rat, Old Man was believed to be 32. ... The Barshop Institute m[aintains] the world's largest mole rat colony. About 2,000 of the tiny, burrowing rodents whose most distinctive feature is their sharp, protruding teeth, live and breed in four basement labs. With their long, hairless bodies and translucent pink skin, they look a bit like Vietnamese spring rolls with legs. ... Because these natives of East Africa live an average 26 years (compared to the 2- to 4-year lifespan of other rodents), they're well-suited for studies of age-related disease. For example, older mole rats develop the same type of brain plaque as that found in Alzheimer's patients. But for reasons unknown, they don't experience similar cognitive decline. Their bones also stay strong and healthy well into their later years. And perhaps most intriguing, mole rats very rarely develop cancer - a common cause of death among other rodents. In fact, when immune-suppressed mice were injected with naked mole rat cells containing tumor-forming genes, they didn't develop cancer. ... Among the many mole rats at the institute, however, Old Man stood out. Because of his advanced age and vigor, he'd claimed a special place in the hearts of many researchers. Laboratory animal attendant Cody Villanueva discovered his body early Thanksgiving morning. 'Oh, it was a sad day,' she recalled. 'I cried. We all did.'"
INVESTIGATING THE DETAILS OF REGENERATION IN LOWER ANIMALS
Wednesday, December 22, 2010
For some years now, researchers have been deciphering the mechanisms of regeneration in lower animals - limbs and organs regrown when lost. Here is an example of the sort of detail work taking place today: "Human regeneration is mainly limited to small portions of liver tissue, bone, or muscle, yet understanding how regeneration occurs in other taxonomic groups may enable scientists to improve human regenerative abilities in the future. ... Lizards can regenerate facial bones, certain areas of the spinal cord, and, as is most commonly known, most lizards can regenerate their tail - including muscles, cartilage, and spinal cord. The regenerated tail does not contain bone, but instead is supported by a tube of hyaline cartilage - the same cartilage humans have lining many of their joints. With widespread medical problems such as arthritis and spinal cord injuries, the application of these regenerative abilities is of extreme interest to medical institutions. .. Many vertebrate and invertebrate species can regenerate tissues, but there are several kinds of regeneration. Lizards most likely use stem-cell mediated regeneration, where new cells involved in regrowth arise from tissue-specific progenitor cells. This type of regeneration is the best bet for a regenerative process compatible with the human system ... the beauty is that now we know enough about development that we can actually have candidates for what cells are making this new tail - we can have guesses as to what might be right. ... Once we understand the nuts and bolts of how this is happening, we can use available technologies to manipulate and change that, then we will try to translate that to the mouse model."
SENESCENT CELLS AND SHORT TERM CALORIE RESTRICTION
Tuesday, December 21, 2010
Researchers run short-term studies on calorie restriction because it's cheaper and faster than long-term studies. Fortunately some of the biological changes brought on by calorie restriction take place fairly rapidly, so this is still a way to learn something. Here is one of the results: "Recent evidence supports the contention that cellular senescence is associated with, and may even be a cause of age-related functional impairment. Senescent cells accumulate in multiple tissues with advancing age. Cellular senescence causes a variety of cell types to acquire a pro-inflammatory secretory phenotype that produce a variety of cytokines, chemokines, and extracellular matrix remodeling proteases that are associated with tissue destruction. Chronic presence of senescent cells can accelerate cancer progression, possibly because of this inflammatory secretory phenotype. Engineered deposition of senescent cells in a single organ, skin, can cause functional impairments in multiple organs similar to those occurring with aging. Finally, senescent cell accumulation in progeroid animal models is associated with dysfunction resembling that of aging. Caloric restriction attenuates processes that have been implicated in cellular senescence, including generation of reactive oxygen species (ROS), growth hormone/insulin-like growth factor-1 signaling, and inflammation. Does caloric restriction in fact reduce cellular senescence? [An] important study [found] short term dietary restriction in middle-aged mice is associated with decreased abundance of senescent cells in the liver (centrilobular hepatocytes) and intestine (crypt enterocytes)."
ALZHEIMER'S AND SLOW GARBAGE REMOVAL
Tuesday, December 21, 2010
Recent research into the causes of Alzheimer's disease: "Do rising brain levels of a plaque-forming substance mean patients are making more of it or that they can no longer clear it from their brains as effectively? ... Clearance is impaired in Alzheimer's disease. We compared a group of 12 patients with early Alzheimer's disease to 12 age-matched and cognitively normal subjects. Both groups produced amyloid-beta (a-beta) at the same average rate, but there's an average drop of about 30 percent in the clearance rates of the group with Alzheimer's. ... Scientists calculate this week [that] it would take 10 years for this decrease in clearance to cause a build-up of a-beta equal to those seen in the brains of Alzheimer's patients. The results have important implications for both diagnosis and treatment. ... Scientists are now interested in learning how a-beta, a byproduct of normal metabolism, is moved out of the brain for breakdown and disposal. As these details come in, they will be essential for physicians working to diagnose the disease before symptoms develop and for drug developers, who can target the problems with pharmaceuticals. A-beta was recognized long ago as a key component of the brain plaques found during autopsies of Alzheimer's patients. One of the ways the brain clears away the a-beta normally produced by brain cell activity is by moving it to the spinal fluid for disposal. Studies have suggested that a drop in spinal fluid levels of a-beta may be a presymptomatic indicator of Alzheimer's disease, possibly because a-beta is getting stuck in the brain and starting to accumulate there." You might also look back at research into the functional decline of the choroid plexus in connection with Alzheimer's: it is a biological filtration system, and its progressive failure may be the cause of lower rates of clearance.
INTIMATIONS OF IMMORTALITY
Monday, December 20, 2010
From Daybreak Magazine: "I think immortality is in the same class as Utopia, infinity and perfection: a great destination to travel to, but one that can never be reached. Yet we should try, nevertheless. While immortality is an unreachable ideal, the effort of reaching it will bring huge progress and immense advantages. So let's be a tad more realistic and call it the quest for longevity, or extreme longevity. Problem is, a lot of people think we shouldn't be on this quest anyway, because of several misconceptions. ... Will McIntosh said (I'm paraphrasing here): "the human psyche is not wired for immortality: in almost every thing we do lies the shadow of our oncoming demise." However, this assumes that humans will not change. I think humans will change. Actually, humans are already changing, and have been changing throughout history. ... it will take time to develop much longer lifespans, followed by extreme longevity. Time enough for humans to change, and to adapt successfully to a much longer life. People have been changing all the time - albeit at a much higher rate in the past 100 years - and have been able to cope. Why shouldn't we be able to do so in the future? ... such thinking - [that] humans will remain the same while the world around them changes - is 'a failure of the imagination'. I agree: by the time extreme longevity is possible, we will have developed the right mindset for it."
DEATH IS A PROBLEM TO BE SOLVED
Monday, December 20, 2010
From Common Sense Atheism: "Let's imagine that every human who had ever lived awoke in the morning with a terrible migraine just behind the eyes for one hour. Nobody could do any work during this time. We just had to endure for one hour, and when it dissipated, go about our business, and dread the next day's migraine. There was no cure for the morning migraine, and none in sight. It was, unfortunately, fixed into the very nature of being human. I have no doubt we would soon begin to rationalize these morning migraines. We would tell ourselves that they make the rest of each day more wonderful by contrast, and that we would not properly appreciate the rest of each day were it not for the migraines. Someone might even venture to say that it's the morning migraines which makes the rest of life meaningful. But now imagine that thousands of years pass, and very advanced scientists discover that morning migraines can be cured - with methods inconceivable to previous generations. Post-migraine generations look back on past generations and wonder: 'How could they tolerate those awful morning migraines? What a horrible way to live, every day! Thank goodness we found a cure!' I want to say the same about death. We rationalize death because we don't think it can be avoided. But death is horrible, like cancer. Death thwarts an awful lot of desires. I don't think much about death, and I don't worry much about it, but I'm sure that when I lie on my deathbed I will have lots more I wanted to do with my life, and not being able to do those things will suck. But here's the good news. Death can be solved."