LONGEVITY MEME NEWSLETTER
January 10th 2011
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.
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- Support Real Progress in Life Extension
- The Simulation Argument
- Subtle Perils of Success
- The Road to Biological Joint Replacement
- Latest Headlines from Fight Aging!
SUPPORT REAL PROGRESS IN LIFE EXTENSION
A good motto to live by:
"As we start the new year, it is helpful to draw attention to the sobering fact that no credible human rejuvenation therapies are available today, and it is doubtful that such therapies will see the light of day in the short term. ... There is a broad consensus in the life extension community that more resources need to be allocated to combating aging as such, as opposed to increasingly futile efforts to extend life by treating aging-associated diseases. Unfortunately, the objective to launch a serious rejuvenation research program has limited mass appeal so far. As a consequence, we will have to get involved ourselves. Hopefully we can shift the focus from extensive hypothetical discussion about the consequences of human enhancement technologies to supporting and engaging in real experimental research to make these technologies facts of life."
THE SIMULATION ARGUMENT
The Simulation Argument is a rather doleful examination of what foreseeable future technologies might tell us about our existential condition:
"In essence, our present trajectory in technology suggests that there is nothing to prevent our descendants from running very detailed simulations of their past, including simulations of people - they will, after all, have access to staggering amounts of processing power, entire solar systems worth of matter converted into high grade nanoscale computing devices. Running a simulation of what is to them early civilized history would be a trivial expenditure given their vast resources, so they will probably do this many, many, many times. Therefore any random pick of what appears to be a human living in the natural universe is actually much more likely to be a simulated human living in a simulated environment.
"This is a modernized and somewhat gloomy brain in a jar scenario: more plausible, given its greater attachment to what we know about technology, and heavier on the existential angst. Either there is no golden future of humanity, or we're most likely participating in it already, but from inside the laboratory and cut off from that reality. Ghosts in the machine.
"[For all such considerations], I think that the best course is to proceed as though what we see is what we get - assume we are in the real world, in these imperfect bodies, faced with real versions of these real challenges of aging and death. To do otherwise is to relinquish our potential, to lie back and relax whilst we are quite literally fighting for our lives."
SUBTLE PERILS OF SUCCESS
To be filed under "eating yourself to death, slowly":
"Advancing medical technology has brought tremendous and accelerating benefits to health and longevity over the past century. The staggering increases in wealth that support that advance introduce more subtle forms of risk to health and wellbeing, however - disease and ill health that is more a matter of what we do to ourselves than what is done to us by various pathogens. Type 2 diabetes, for example, is a lifestyle condition that is essentially caused by eating too much over a long enough period of time. Adopt the right lifestyle and you are very unlikely to suffer its effects. Yet so very many people have type 2 diabetes - and as the population of various regions of the world move from being poor to being wealthy, they suffer ever more from these sorts of medical conditions, even as their lifespans increase.
"It is clearly the case that failing to be more successful and wealthy than your ancestors is worse than having the opportunity to eat yourself into an expensive and debilitating degenerative condition - but why sabotage the benefits that you do have? Most of us should know better, but the siren call of low-cost calories and luxurious laziness is very effective. Still, it is a choice. We have willpower and the free will with which to use it. You can blame your genes and circumstances if you like, but that's just as much a choice as it is to surmount those challenges to stay lean and healthy."
THE ROAD TO BIOLOGICAL JOINT REPLACEMENT
Tissue engineers focused on the so far challenging area of growing new cartilage have made steady progress over the past few years. Now they're demonstrating some fairly advanced applications in laboratory animals:
"Artificial joint replacements can drastically change a patient's quality of life. Painful, arthritic knees, shoulders and hips can be replaced with state-of-the-art metal or ceramic implants, eliminating pain and giving a person a new lease on life. But, what if, instead of metal and plastic, doctors were able to take a patient's cells and grow an entirely new joint, replacing the old one with a fully functional biological joint? A team of University of Missouri and Columbia University researchers have found a way to create these biological joints in animals, and they believe biological joint replacements for humans aren't far away."
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!
MITOCHONDRIA, HORMESIS, AND LIFESPAN
Friday, January 7, 2011
While we're on the subject of mitochondrial processes leading to signals that change life span: "An unequivocal demonstration that mitochondria are important for lifespan comes from studies with the nematode Caenorhabditis elegans. Mutations in mitochondrial proteins such as ISP-1 and NUO-6, which function directly in mitochondrial electron transport, lead to a dramatic increase in the lifespan of this organism. One theory proposes that toxicity of mitochondrial reactive oxygen species (ROS) is the cause of aging and predicts that the generation of the ROS superoxide should be low in these mutants. Here we have measured superoxide generation in these mutants and found that it is in fact elevated, rather than reduced. Furthermore, we found that this elevation is necessary and sufficient for longevity, as it is abolished by antioxidants and induced by mild treatment with oxidants. This suggests that superoxide can act as a signal triggering cellular changes that attenuate the effects of aging. This idea suggests a new model for the well-documented correlation between ROS and the aged phenotype. We propose that a gradual increase of molecular damage during aging triggers a concurrent, gradually intensifying, protective superoxide response."
RESEARCH IN MITOCHONDRIAL SIGNALS AND EXTENDED LIFESPAN
Friday, January 7, 2011
This is interesting research: scientists "used the roundworm Ceanorhabditis elegans to show that perturbing mitochondrial function in subsets of worm cells sent global signals governing longevity of the entire organism. ... In this study we show how signals sent from distressed mitochondria are communicated to distant tissues to promote survival and enhance longevity ... The identity of the signal sent from mitochondrially-distressed cells - a hypothetical factor Dillin calls a 'mitokine' - remains unknown. Nonetheless, he speculates that mitokines could one day be lobbed as messengers from healthy to unhealthy tissues to treat degenerative conditions. ... Imagine if we could perturb mitochondria in the liver, and make them send a mitokine to degenerating neurons. Instead of trying to get a drug into the brain, we could exploit the body's ability to send out a natural rescue signal. ... many investigators, Dillin included, have observed puzzling relationships between mitochondria, energy generation and longevity-interactions that suggest that living long does not necessarily require prospering at the subcellular level. ... As a postdoctoral fellow I did a screen looking for worm genes that increased longevity. Many genes were related to mitochondrial function. If you disabled them, worms lived longer, although their respiration or metabolism was reduced. We wondered whether this is why animals lived longer. ... To determine how cells respond to the pro-longevity cue, the group monitored a cellular emergency plan called the Unfolded Protein Response (UPR). Cells mount it when proteins accumulate excessively and begin to unravel - or 'misfold' - which is toxic to cells. To avert cell death, the UPR mobilizes a team of helpers who, like sales clerks at a Gap sweater table, refold accumulating misfolded proteins piling up inside a cell. When Dillin and colleagues fed worms reagents blocking the UPR, they found that disruption of [mitochondrial activity] in neurons or intestine no longer had a lifespan-enhancing effect. This dramatic finding illustrates that initiating refolding of proteins, in this case in response to faraway mitochondrial stress, is in fact the very activity that enhances longevity." You might compare this to the benefits of autophagy, another housekeeping and repair activity that takes place inside cells.
WHY ISN'T MORE BEING DONE NOW TO HELP THE AGED?
Thursday, January 6, 2011
Researcher Tom Kirkwood here argues that lack of progress in aging and longevity science is only one manifestation of our communal lack of interest in providing tools to enable a better life for the old and the frail: "Although there are many who think that ageing begins at 40, 50 or 60, we are learning that the underpinning mechanisms of ageing play out throughout the life course. Appreciating the life course nature of ageing helps surmount the objection sometimes raised against research on ageing, namely, that we should set a lower priority on research for old people who have had their 'innings' already. Indeed, if we can deliver a world that gives greater health to older people, it will be our children and grandchildren who will benefit the most. We age, not because our genes programme our death but because our bodies accumulate a growing burden of faults in their cells, tissue and organs. ... Often, a relatively simple modification of the environment can remove what was previously an insuperable obstacle, an obvious example being, for a wheelchair user, the provision of a ramp and a door wide enough to take a wheelchair. For a person with arthritis of the hand, use of a conventional mobile phone may be impossible, so such a person is disabled with respect to making telephone calls while on the move. However, simple technological solutions exist, at least in principle, for this problem. Technology, properly developed and applied, will liberate large numbers of older people from entirely unnecessary social isolation and enforced dependency. The result, even if the technology solutions were funded entirely by the state resources, would be savings in the provision of high- dependency support services that would easily repay the necessary investments. However, there is no need to see the future provision of technology solutions as requiring state support. The market opportunities for companies are enormous already and growing every year. It is hard to escape the impression that what is holding these developments back is nothing less than a pervasive lack of imagination, propelled perhaps by equally pervasive ageism. It is here that there is a role for us all in fighting for the necessary change in attitude and effective commitment to fresh action."
HUMANITY+ CONFERENCE IN LONDON
Thursday, January 6, 2011
From h+ Magazine: "People who are new to Humanity+ and to transhumanist thought in general might well be under the impression that the H+ movement is primarily an American beast. Optimism with regard to the future seems to be part of the American psyche, so I was surprised when I learned that H+ began its existence as the World Transhumanist Association, founded in the UK by philosophers David Pearce and Nick Bostrom in 1998. Ten years later, the organisation was renamed to Humanity Plus, and the first UK conference for H+ was held in London in April 2010. The first H+ conference of 2011 will also be held in London on January 29th, building upon the success of last year's meeting, and promises to be a fascinating exchange of ideas. ... [Amongst the topics] is the popular transhumanist topic of life extension. Dr Marios Kyriazis will be talking about how the convergence of different areas of science may allow dramatic life extension, and will briefly discuss some of the implications to our society. Following from Marios' talk, Dr Aubrey de Grey will give a presentation on some of the latest developments in the field of life extension, explaining that if we are able to extend our lives by more than one year per year of progress, we can achieve a longevity escape velocity and potentially live for a very long time indeed."
STEM CELLS AND BALDNESS
Wednesday, January 5, 2011
It is revealing that stem cell research into therapies for baldness attracts far more public and media attention than stem cell therapies for heart conditions - human nature and human priorities are not what they might be. That aside, progress is occurring here just as in other areas of regenerative medicine: "Common baldness could have its roots in a newly identified stem cell defect, a finding that could potentially lead to new hair-loss treatments down the road ... Researchers say they discovered that a cellular malfunction short-circuits the process by which hair follicle stem cells turn into hair-producing progenitor cells. That defect, rather than any loss of stem cells themselves, sparks the onset of androgenic alopecia, the medical term for a type of genetic hair loss that affects both men and women ... In men, this hair loss is commonly known as male pattern baldness, marked by the familiar receding hairline and thinning hair on top of the head - a condition that sometimes leads to complete baldness. In women, female-pattern hair loss causes the hair to get thinner all over but rarely leads to baldness. ... Previously we thought the stem cells were gone, and if that was the case it would be very difficult. But because they are present it should be possible to treat ... A complex series of analyses revealed that bald and haired tissue contain equivalent amounts of preserved stem cells, which give rise to progenitor cells. Bald tissue, however, did not contain the normal amount of progenitor cells, suggesting a malfunction in the normal behavior of hair follicle stem cells. ... The follicles that make hair don't go away completely, but they become miniaturized, to the point where the hair they normally make to replace hair when it naturally falls out becomes microscopic and therefore invisible."
THERE ARE MANY GOOD BIOMARKERS FOR AGE-RELATED FRAILTY
Wednesday, January 5, 2011
Good measures of frailty in age, and good correlations with mortality rate, have been comparatively easy for the medical establishment to discover and verify - take grip strength, for example. Here is another: "In an analysis of nine studies involving more than 34,000 people age 65 and older, faster walking speeds were associated with living longer: Predicted years of remaining life for each age and both sexes increased as gait-speed increased, with the most significant gains after age 75. In addition, researchers found that predicting survival based on gait speed was as accurate as predictions based on age, sex, chronic conditions, smoking history, blood pressure, body mass index and hospitalization. ... Walking is a reliable tool to measure well-being [because] it requires body support, timing and power, and places demands on the brain, spinal cord, muscles and joints, heart and lungs. Slowing down is associated with getting older. By age 80, gait speed is approximately 10% to 20% slower than in young adults. ... In the study, gait speed was calculated using distance in meters and seconds. All subjects were instructed to walk at their usual pace and from a standing start. Average rate of speed was 3 feet per second (about 2 miles an hour). During the 14-year course of the study, there were 17,528 deaths. Those who walked slower than 2 feet per second (about 1.36 miles an hour) had an increased risk of dying. Those who walked 3.3 feet per second (about 2.25 miles per hour) or faster survived longer than would be expected by age or sex alone." Eliminating the slow spiral down into frailty and physical incapacity is one of the noble goals of longevity science.
ON STEM CELL AGING
Tuesday, January 4, 2011
Stem cells work to maintain your tissues, but their ability to carry out their job diminishes with age, causing a corresponding decline in tissue function. An understanding of why stem cell decline occurs is important in determining what to do about the problem. For example, if the problem is damage in the stem cells themselves, then replacement is a very viable option. If, however, the issue is caused by broader damage in supporting cell populations that leads important signaling processes and stem cell niches to run awry, a completely different strategy is needed. Researchers do not yet have a full understanding as to the mechanisms by which stem cells decline with age, but they are working on it: "Stem cell aging is a novel concept that developed together with the advances of stem cell biology, especially the sophisticated prospectively isolation and characterization of multipotent somatic tissue stem cells. Although being immortal in principle, stem cells can also undergo aging processes and potentially contribute to organismal aging. The impact of an age-dependent decline of stem cell function weighs differently in organs with high or low rates of cell turnover. Nonetheless, most of the organ systems undergo age-dependent loss of homeostasis and functionality, and emerging evidence showed that this has to do with the aging of resident stem cells in the organ systems. The mechanisms of stem cell aging and its real contribution to human aging remain to be defined. Many antitumor mechanisms protect potential malignant transformation of stem cell by inducing apoptosis or senescence but simultaneously provoke stem cell aging."
DNA DAMAGE, CANCER, AND AGING
Tuesday, January 4, 2011
A short open access paper: "Defects in the DNA damage response often lead to an increased susceptibility to cancer, and so the DDR presents an interesting set of novel therapeutic targets. The maintenance of genomic integrity by the DDR has also been found to be involved in the process of organismal ageing. While the removal of cells containing damaged DNA can be beneficial in the prevention of cancer, it may contribute to both normal and pathological ageing. ... Given the frequency at which DNA lesions occur (approximately 10^4 per cell per day), a complex system of damage detection and repair is required in order to preserve the integrity of the genome. This system is termed the DNA damage response (DDR), and encompasses: the recognition of DNA damage; the transduction of signals through appropriate pathways; and the activation of cellular responses ranging from DNA repair and chromatin remodeling to the activation of cell death if the damage is irreparable. ... The maintenance of the DDR is essential for faithful replication of the genome, and so is critical for cellular survival. The loss of certain DDR components can lead to an increased susceptibility to cancer due to the ensuing genomic instability and the subsequent mutation to genes required for cellular replication and division. The DDR is also involved in the induction of senescence and apoptosis when the damage cannot be repaired. While this can prolong longevity during early stages of life due to the suppression of tumorigenesis, it may become detrimental in ageing due to the loss of stem and progenitor cells for renewal. This is a phenomenon referred to as antagonistic pleiotropy, and it highlights the importance of carefully balanced cell signaling cascades and regulatory systems in the maintenance of survival. Further studies of the roles of DDR-associated proteins, along with the discovery of new ones, will therefore not only enhance our understanding of cancer and mechanisms to treat it, but will also enhance our understanding of the ageing process. This may uncover ways to treat premature ageing or other age-related pathologies, such as the decline of the immune system in the elderly."
LESSONS ON REGROWTH
Monday, January 3, 2011
From the Boston Globe: "The dream of regenerative medicine is that it will one day be possible to replace flawed tissues - to create a new spinal cord, repair a defective heart, or regrow a limb. But as scientists make steady progress toward that tantalizing goal, some are studying a range of simple organisms, from tadpoles to salamanders to flatworms, that can already rebuild complete limbs or tails. In his laboratory at Tufts University, biology professor Michael Levin is investigating an often-overlooked mechanism that may play a key role in triggering this regenerative capacity in such critters: electrical signals. When people think of electricity in the body, they usually think of brain and nerve cells, or muscles. But Levin and other scientists study the bioelectrical signals that exist in all cells, and the role those play in allowing organisms to generate precise, functional replacements for body parts. ... Levin has altered the electrical signaling in cells and observed dramatic effects: A tadpole can regenerate a completely normal tail after it has lost that ability. ... Levin and colleagues triggered that regeneration using drugs that affected the bioelectrical signaling in tadpoles. The drug increased the transport of sodium into cells, triggering the tadpoles to regrow perfectly formed tails, which include a complex mixture of tissues including spinal cord, muscle, and skin. Levin's hope is that electrical signals might be a master switch that allows the organism to boot up its regenerative program, rather than requiring scientists to build a new organ or appendage cell by cell."
WHY LONGEVITY-ENHANCING GENES ARE NOT SELECTED BY EVOLUTION
Monday, January 3, 2011
Longevity may or may not be advantageous from an evolutionary point of view - it depends on the circumstances, which is why we see a wide variety of life spans in nature. Many species can be genetically altered in minor ways to live for longer in good health. One possible reason why these longevity-enhancing mutations don't occur in nature is that they may diminish an organism's reproductive vigor while young: "Reduced fecundity has been associated with some alleles that enhance longevity in invertebrate and mammalian models. This observation has been suggested to support the antagonistic pleiotropy theory of aging, which predicts that alleles of some genes promoting fitness early in life have detrimental effects later in life that limit survival. In only a few cases, however, has the relative fitness of long-lived mutants been quantified through direct competition with the wild type genotype. Here we report the first comprehensive analysis of longevity/fitness trade-offs by measuring the relative fitness of 49 long-lived yeast variants in a direct competition assay with wild type cells. We find that 32 (65%) of these variants show a significant defect in fitness in this competition assay. In 26 (81%) of these cases, this reduction in fitness can be partially accounted for by reduced maximal growth rate during early life, usually resulting from a G0/G1-specific cell cycle defect. A majority of the less fit longevity-enhancing variants are associated with reduced mRNA translation. These findings are therefore consistent with the idea that enhanced longevity often comes with a fitness cost and suggest that this cost is often associated with variation in a subset of longevity factors, such as those regulating mRNA translation, growth, and reproduction."