LONGEVITY MEME NEWSLETTER
August 02 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.
- The Rift in Longevity Science
- p53 and Aging
- Spurring Joint Regeneration
- The Tedium of Debating Boredom
- Latest Healthy Life Extension Headlines
THE RIFT IN LONGEVITY SCIENCE
A recent review cuts right to the point:
"Gerontology expert Aubrey de Grey, long dismissed as a fringe thinker in the field because he doesn't think we should have to age at all, believes it will be a short leap from a 150-year lifespan to 1000. He notes that, with the speed of the current research, 'If you're only 50, ... there's a chance you could pull out of the dive.' He is beginning to be considered more mainstream. The current rift between de Grey's philosophy and the other scientists, records Pappas, is that de Grey wants to get rid of aging altogether, while they just want to extend a healthy lifespan."
This is the most important division in modern aging research. Will resources be directed to slow aging or repair and reverse the damage of aging? Either path will be successful on a time scale of decades, if fully funded, but the end results will be very different.
"It is likely to be easier and less costly to produce rejuvenation therapies than to produce a reliable and significant slowing of aging. A rejuvenation therapy doesn't require a whole new metabolism to be engineered, tested, and understood - it requires that we revert clearly identified changes to return to a metabolic model that we know works, as it's used by a few billion young people already. Those rejuvenation therapies will be far more effective than slowing aging in terms of additional years gained, since you can keep coming back to use them again and again. They will also help the aged, who are not helped at all by a therapy that merely slows aging."
We know that most of us reading this today will be a good twenty years older by the time the first useful longevity therapies emerge. If those therapies can do no more than slow aging, then we will gain little to no benefit from them.
P53 AND AGING
Careful manipulation of the p53 gene has been demonstrated to significantly extend life in mice. Here is an introduction to its importance:
"The cancer suppressor gene p53 has proven to be the center of a fruitful area of study in aging research: it is a master controller or important component in many critical biological processes - such as cell division, and even autophagy. While levels of p53 expression were thought to operate as a sliding scale between more cancer and slower aging at one end versus less cancer and faster aging at the other, researchers have in recent years demonstrated clever ways around this evolutionary trade-off. So gene-engineered mice have been created that suffer less cancer and still live longer."
SPURRING JOINT REGENERATION
Researchers are becoming more adept at inducing existing cell populations in the body to regenerate damage that would not ordinarily have healed:
"Researchers are reporting they have successfully persuaded damaged joints to regrow cartilage and bone, using a novel "cell homing" approach. The experiments, conducted in rabbits, are a proof of concept of a method that may one day replace artificial joint transplants in humans ... The method uses a carefully constructed 'bioscaffold,' impregnated with a growth factor that causes precursor cells to migrate to the site and become cartilage and bone cells ... Animals treated with the method fully recovered weight-bearing and locomotion within a month, and the regenerated tissue was similar to naturally occurring cartilage and bone, the researchers said."
THE TEDIUM OF DEBATING BOREDOM
Too many talking heads seem to think that any large increase in human life span would lead to boredom:
"There really isn't much to it: one side says, without any real evidence to back it up, that longer lives will inevitably lead to the boredom of repetition, and a dulled, meaningless existence. Those of us with more sense and imagination pull out the numbers to show that this viewpoint is nonsense however you choose to look at it. There is more to be experienced than any person could undertake in a million years, even in this limited world of ours today."
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 HEALTHY LIFE EXTENSION HEADLINES
LESSONS FROM THE MOUSE (July 30 2010)
A reminder of the role of the laboratory mouse in aging research: "Aging, which affects all organ systems, is one of the most complex phenotypes. Recent discoveries in long-lived mutant mice have revealed molecular mechanisms of longevity in mammals which may contribute to our understanding of why humans age. These mutations include naturally-occurring spontaneous mutations, and those of mice genetically modified by modern genomic technologies. It is generally believed that the most fundamental mechanisms of aging are evolutionarily conserved across species. The following types of longevity mechanisms have been intensively studied: suppression of the somatotropic (growth hormone/insulin-like growth factor 1) axis, decreased metabolism and increased resistance of oxidative stress, reduced insulin secretion and increased insulin sensitivity, and delayed reproductive maturation and reduced fertility. In addition, many of the mutations have a sex-dependent effect on lifespan, and when present in different genetic backgrounds, the effects of the same gene mutation can vary considerably. ... We anticipate that these mouse studies will ultimately provide clues about how to delay the aging and prolong lifespan, and help to develop therapies for healthier human aging."
AGING OF THE INNATE IMMUNE SYSTEM (July 30 2010)
The innate immune system declines with age, just like the adaptive immune system. The details are different: "The innate immune system is composed of a network of cells including neutrophils, NK and NKT cells, monocytes/macrophages, and dendritic cells that mediate the earliest interactions with pathogens. Age-associated defects are observed in the activation of all of these cell types, linked to compromised signal transduction pathways including the Toll-like Receptors. However, aging is also characterized by a constitutive pro-inflammatory environment (inflamm-aging) with persistent low-grade innate immune activation that may augment tissue damage caused by infections in elderly individuals. Thus, immunosenescence in the innate immune system appears to reflect dysregulation, rather than exclusively impaired function." Understanding the cause of the problem steers the search for solutions. Dysregulation means that the focus is on fixing errant signaling mechanisms, or on finding ways to directly instruct cells to act or not act. Cell transplants or repairs are not much use if the problem actually lies in the control systems.
HARNESSING HORMESIS (July 29 2010)
Hormesis is here examined in the context of exploiting it to slow aging: "The process of aging is accompanied by a progressive reduction of biological dynamical sophistication, resulting in an increased probability of dysfunction, illness, and death. This loss of sophistication is inherent in all aging organisms. However, it may be possible to retard the rate of loss of biological complexity [by] exploiting the multiple effects of hormesis, through a wide range of challenges including physical, mental, and biological stress. Hormesis is widely encountered in biological systems, and its effects are also seen in humans. It is possible to use hormetic strategies [to] enhance the function of repair processes in aging humans and therefore prevent age-related chronic degenerative diseases and prolong healthy lifespan. Such techniques include dietary restriction and calorie restriction mimetics, intermittent fasting, environmental enrichment, cognitive and sense stimulation, sexuality-enhancing strategies, exposure to low or to high temperatures, and other physicochemical challenges. Current research supports the general principle that any type of a hormetic dose-response phenomenon has an effect that does not depend on the type of stressor and that it can affect any biological model. Therefore, novel types of innovative, mild, repeated stress or stimulation that challenge a biological system in a dose-response manner are likely to have an effect that, properly harnessed, can be used to delay, prevent, or reverse age-related changes in humans."
AN EXAMPLE OF EARLY LIFE DAMAGE AFFECTING LONGEVITY (July 29 2010)
Per the reliability theory of aging, we should expect to see shorter life expectancies result from damage or stress in early life. Here, a historical analysis supports that line of thinking: "Nutritional conditions in utero and during infancy may causally affect health and mortality during childhood, adulthood, and at old ages. This paper investigates whether exposure to a nutritional shock in early life negatively affects survival at older ages, using individual data. Nutritional conditions are captured by exposure to the Potato famine in the Netherlands in 1846-1847, and by regional and temporal variation in market prices of potato and rye. The data cover the lifetimes of a random sample of Dutch individuals born between 1812 and 1902 and provide individual information on life events and demographic and socioeconomic characteristics. First we non-parametrically compare the total and residual lifetimes of individuals exposed and not exposed to the famine in utero and/or until age 1. Next, we estimate survival models in which we control for individual characteristics and additional (early life) determinants of mortality. We find strong evidence for long-run effects of exposure to the Potato famine. The results are stronger for boys than for girls. Boys and girls lose on average 4, respectively 2.5 years of life after age 50 after exposure at birth to the Potato famine. Lower social classes appear to be more affected by early life exposure to the Potato famine than higher social classes. These results confirm the mechanism linking early life (nutritional) conditions to old-age mortality."
CONSIDERING CRYONICS AND NEURONAL SURVIVAL (July 28 2010)
From Depressed Metabolism: "The debilitating effects of a stroke are the result of the (delayed) neuronal death that follows an ischemic insult to the brain. In cryonics, biochemical or freezing damage to cells does not necessarily produce irreversible cell death because damaged cells are stabilized by cold temperatures. As such, morphological preservation of brain cells can co-exist with loss of viability. Therefore, securing viability of brain cells is a sufficient but not a necessary condition for resuscitation of cryonics patients. Future cell repair technologies are assumed to infer the original viable state of the cells from their morphological properties. This does not mean that conventional stroke research does not have any relevance for evaluating the technical feasibility of cryonics. Extensive delays between the pronouncement of legal death and the start of cryonics procedures could alter the structural properties of cells to such a degree that meaningful resuscitation is even problematic with advanced nanomedical cell repair technologies. This is one of the reasons why Alcor complements the cryopreservation process with stabilization procedures to secure viability of the brain after pronouncement of legal death."
SOCIAL CONNECTIVITY AND MORTALITY RISK (July 28 2010)
This study crunches the numbers to show that being socially connected has an effect on life expectancy comparable to that of exercise. Why this correlation exists is still up for debate, but it is worth considering that skill at networking and possessing a large social network enable success in other aspects of life: "These findings indicate that the influence of social relationships on the risk of death are comparable with well-established risk factors for mortality such as smoking and alcohol consumption and exceed the influence of other risk factors such as physical inactivity and obesity. Furthermore, the overall effect of social relationships on mortality reported in this meta-analysis might be an underestimate, because many of the studies used simple single-item measures of social isolation rather than a complex measurement. Although further research is needed to determine exactly how social relationships can be used to reduce mortality risk, physicians, health professionals, educators, and the media should now acknowledge that social relationships influence the health outcomes of adults and should take social relationships as seriously as other risk factors that affect mortality, the researchers conclude."
EXERCISE: GOOD AT ANY AGE (July 27 2010)
Failing to exercise damages your prospects for healthy life in the future: "one in three men and one in two women over the age of 75 are not physically active at all. A recent study led by the National Institute on Aging (NIA) says this lack of exercise makes these seniors three times more likely to die sooner than their counterparts who do only light day-to-day activities. ... Any movement is better than no movement at all to lower your risk of death ... For every 287 calories per day a senior expended, there was a 32 percent reduction in death rate over the six-year period encompassed by the study. ... It is well-established that exercise leads to the reduction of heart disease, cancer and diabetes, and it can preserve mental sharpness. What is significant about the current findings is that the study is the first to provide credible evidence that everyday activity might be beneficial ... Researchers ask how much activity do we need, but the public approaches it by asking how little can I get away with ... experts caution against using the study as a basis to give up exercise, a conclusion not supported by the data." A little is better than none, but more is better than a little. Rejuvenation medicine is on the far horizon, and if you want the best chance of being alive and healthy to benefit from it, you'd better take care of the health basics here and now.
LYSOSOMAL DYSFUNCTION AND ALZHEIMER'S DISEASE (July 27 2010)
Your lysosomes are recycling units, but their function slowly fails with age - meaning your cells degrade as they fill with waste and junk. More rapid and selective lysosomal failure in brain cells is implicated in a variety of neurodegenerative conditions. Here, researchers dig more deeply: "Neurodegenerative disorders, like Alzheimer's disease, are a devastating group of conditions that exact a heavy toll on patients and their families. ... Research over the past two decades has strongly suggested that a fundamental problem in affected nerve cells relates to accumulation of cellular 'garbage,' or proteins and other material that is too old to function properly. Thus, understanding how the neuron handles these outdated molecules is of great significance. Here we find that upregulation of one such cellular degrading pathway, the lysosome, can have significant deleterious effects to the neuron. We specifically show that expanding the lysosomal compartment can markedly increase production of a very toxic form of tau, a protein strongly implicated in neuronal dysfunction and death in Alzheimer's disease and related disorders. Our findings have important implications for the development of neurodegenerative disease therapies that seek to manipulate the lysosome and the proteins within the lysosome." Therapies that can repair failing lysosomes may have general application to rejuvenation medicine - so the more groups working on that, the better.
WHY PAY ATTENTION TO ACCELERATED AGING STUDIES? (July 26 2010)
In a nutshell, this is why research into so-called accelerated aging conditions may be relevant to longevity science: "One of the many debated topics in ageing research is whether progeroid syndromes are really accelerated forms of human ageing. The answer requires a better understanding of the normal ageing process and the molecular pathology underlying these rare diseases. Exciting recent findings regarding a severe human progeria, Hutchinson-Gilford progeria syndrome, have implicated molecular changes that are also linked to normal ageing, such as genome instability, telomere attrition, premature senescence and defective stem cell homeostasis in disease development. These observations, coupled with genetic studies of longevity, lead to a hypothesis whereby progeria syndromes accelerate a subset of the pathological changes that together drive the normal ageing process." This same viewpoint - that each of the accelerated aging conditions represents a different facet of normal aging run wild - holds up for well other conditions, such as Werner syndrome, given the evidence amassed to date.
MDR PROTEINS AND CELLULAR LONGEVITY (July 26 2010)
An interesting study that provides another view of the relationship between accumulating damage, repair systems, and life span in cells: "Yeast cells, much like our own cells, have a finite ability to reproduce themselves. A 'mother' cell can only produce 20-30 'daughters' before it loses the ability to replicate and dies. ... Multidrug resistance (MDR) proteins are best known for helping cancer cells expel anticancer drugs - hence their name - but they also ferry compounds in and out of normal cells. [Researchers] found that yeast lacking certain MDR proteins have a shorter reproductive lifespan; they produce fewer daughter cells. Yeast engineered to contain more of these pumps, however, can produce more daughters. ... during division, the mother conserves damaged proteins and other cellular components that could prove harmful to the bud. ... Indeed, some research groups have posited that the mother's finite reproductive capability is the result of accumulating these damaged and toxic compounds. ... yeast division also results in an unequal distribution of MDR proteins. The mother cell retains the original MDR proteins while the bud gets young, newly formed MDR proteins. Because the mother's supply is never replenished, she has to rely on the pool of MDR proteins that she's born with. ... Over time these proteins decay. Some lose only part of their function; others may stop working altogether."