10.31.08
Posted in Uncategorized at 11:15 am by heaven
A couple of papers to compare and contrast:
Melatonin in relation to the "strong" and "weak" versions of the free radical theory of aging:
While the data supporting a role for melatonin in forestalling aging and prolonging life span per se is not compelling, the findings related to melatonin's ability to reduce the severity of a variety of age-related diseases that have as their basis free radical damage is convincing.
Melatonin prevents age-related mitochondrial dysfunction in rat brain via cardiolipin protection
Melatonin has been shown to possess antioxidant properties and to reduce oxidant events in brain aging. .... We found [that a number of] mitochondrial parameters were significantly altered with aging, and that melatonin treatment completely prevented these age-related alterations. These effects appear to be due, at least in part, to melatonin's ability to preserve the content and structural integrity of cardiolipin molecules, which play a pivotal role in mitochondrial bioenergetics.Which is interesting to say the least; I would have lumped melatonin in with all the other antioxidant supplements - just because a chemical happens to affect some aspects of your biochemistry doesn't mean that ingesting it is going to have any positive benefit.
I have to wonder at what complexity is hidden here: a mechanism completely prevents alterations in mitochondrial parameters, and yet doesn't do anything for life span? Compare that with antioxidant chemicals targeted directly to mitochondria, which lead to significant extensions of healthy life. Mitochondria are complex objects, and (a) the state of their membranes, (b) the working of their inner processing mechanisms, and (c) the effects they have on their cell are not linked in straightforward ways.
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Posted in Uncategorized at 11:15 am by heaven
The rational actor looks at risks to life and health ahead and acts to minimize those risks. Since we all have limited time and resources, we have to prioritize: we make lists, in our heads if nowhere else, putting the most likely and terrible outcomes up at the top. Highly unlikely but terrible outcomes don't receive much attention: meteors, lightning strikes, that sort of thing. Likely but merely unpleasant events might just be suffered as a cost of getting on with life: catching the flu is an obnoxious happenstance, but not particularly threatening for most of us. There are more important things to worry about while buying insurance and otherwise taking care of essentials.
So you end up with a list involving fires, car accidents, sudden implosion of the company you work for, that sort of thing. In that, most of us are not being terribly rational, as aging isn't on the list. It is absolutely going to happen, and it leads to the most terrible personal consequence possible - death - via numerous other very nasty personal consequences. Alzheimer's, heart disease, cancer, and all the rest. We all have a 100% chance of aging as things stand, and it's the worst thing that will happen to most of us. So why isn't it up near the top of that priority list?
On that subject, thoughts from a bioethicist I seem to be linking to a lot of late. Replace "we" with "I" and "society" with "an individual" and it works just fine:
the following four issues are vital: 1. The certainty of the harm (e.g. 0.1% vs 70% chance)
2. The severity of the harm (e.g. broken leg vs death)
3. The likelihood of mitigating the harm (e.g. 0.1% vs 70%)
4. The cost of mitigating the harm ($1 billion vs $1 trillion)
...
Aging increases ones risk of disease and death. So the empirical evidence clearly shows that aging scores very high on (1) and (2). These facts alone show that aging is a BIG problem.
How about issues (3) and (4)? People are most likely to (mistakenly) assume aging research scores low on both these fronts. That is, people are skeptical that we can actually modify the biological processes of aging. But there are countless experiments in a variety of organisms that show aging is not immutable. And so the goal of retarding human aging scores reasonably well on (3). And once you add considerations (1) and (2) into the mix, it becomes evident that the current neglect of aging research is unjustified.
People will also falsely assume that (4) will require vast amounts of money. But here one must put things in their proper context. A lot of money compared to what? What we spend on national defence? National defense spending in the U.S. has reached approximately $1,600 per capita, compared to $97 per capita for federal spending on biomedical research (source)
Which I think is a fair summary of where things stand - aging is terrible, but those who would act to materially support longevity science don't believe that progress is possible, or that progress is cost-effective. Meanwhile, individuals pledge significant time and money for food, entertainment, and geopolitical machinations. You might want to refresh your memory as to the Strategies for Engineered Negligible Senescence (SENS) cost breakdown: a billion dollars over ten years to develop the medical technologies capable of rejuvenating aged mice in the laboratory, each of the seven branches of SENS requiring something like $15 million per year over that time.
Effective research is cheap compared to almost everything else connected with aging: the loss of wealth, deteriorating health, loss of contributing members of society, the elderly care infrastructure, and more. It's a great pity that support and fundraising lags so far behind the potential of longevity science.
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10.29.08
Posted in Uncategorized at 11:14 am by heaven
Mainstream research on the biochemistry of aging and longevity - with
an eye to slowing down aging rather than repairing it - is at this time primarily focused on a small number of areas. One is the cluster of mechanisms and signaling pathways associated with
insulin and
insulin-like growth factor 1 (IGF-1). You might recall that a tenfold increase in nematode life span
was engineered via manipulation of IGF-1, for example:
Reis' team discovered that a mutant in the insulin/ IGF-1 pathway of C. elegans slows development but ultimately produces adults he described as "super survivors," able to resist levels of toxic chemicals that would kill an ordinary worm. Although the adult lifespan of C. elegans is normally only two to three weeks, half of the mutant worms were still alive after six months, with some surviving to nine months.While perusing PubMed, I noticed a couple of papers on insulin, IGF-1, and aging:
Insulin and aging
In invertebrates, signaling pathways homologous to mammalian insulin and insulin-like growth factor (IGF-1) signal transduction have a major role in the control of longevity. There are numerous indications that these pathways also influence aging in mammals, but separating the role of insulin from the effects of IGF-1 and growth hormone (GH) is difficult.
In mice, selective disruption of the insulin receptor in the adipose tissue extends longevity. Increases in lifespan were also reported in mice with deletion of insulin receptor substrate 1 (IRS1) in whole body or IRS2 only in the brain. GH deficiency or resistance in mutant mice leads to hypoinsulinemia and enhanced insulin sensitivity along with remarkably extended longevity.
These characteristics resemble animals subjected to calorie restriction. Studies of physiological characteristics and polymorphisms of insulin-related genes in exceptionally long-lived people suggest a role of insulin signaling in the control of human aging.
Role of the GH/IGF-1 axis in lifespan and healthspan: Lessons from animal models
Consistently, two interventions, caloric restriction and repression of the growth hormone (GH)/insulin-like growth factor-1/insulin axis, have been shown to increase lifespan in both invertebrates and vertebrate animal model systems. Caloric restriction (CR) is a nutrition intervention that robustly extends lifespan whether it is started early or later in life. Likewise, genes involved in the GH/IGF-1 signaling pathways can lengthen lifespan in vertebrates and invertebrates, implying evolutionary conservation of the molecular mechanisms. Specifically, insulin and insulin-like growth factor-1 (IGF-1)-like signaling and its downstream intracellular signaling molecules have been shown to be associated with lifespan in fruit flies and nematodes. More recently, mammalian models with reduced growth hormone (GH) and/or IGF-1 signaling have also been shown to have extended lifespans as compared to control siblings. Importantly, this research has also shown that these genetic alterations can keep the animals healthy and disease-free for longer periods and can alleviate specific age-related pathologies similar to what is observed for CR individuals. Thus, these mutations may not only extend lifespan but may also improve healthspan, the general health and quality of life of an organism as it ages.
With the level of interest presently devoted to this subject, I imagine that a decade from now researchers will fully understand how IGF-1, insulin, growth hormone, and calorie restriction all fit together into the bigger picture of the natural range of metabolic processes in response to circumstances. Your diet and exercise choices change the way your biochemistry operates: the biochemical mechanisms by which this happens have a deep evolutionary history.
It seems evident that some large portion of the research community will continue to forge ahead with strategies to shift your metabolism into a better state for your long term health - replicating calorie restriction, or mutations known to be beneficial. This is not a path to radical extension of the healthy human life span, however. It will only produce modest gains. To move beyond the small goals, we have to aim to repair the damage of aging rather than just slow down its accumulation. It will be no harder to achieve from where we are now, and the rewards are far greater.
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Posted in Uncategorized at 11:14 am by heaven
The
latest Rejuvenation Research is available online; I'm interested to note the contribution of another
"social justice"-style bioethicist. Regular positive engagement with the ideas and goals of longevity science is a
fairly recent phenomenon for that portion of the social studies crowd; while their ideas are just as contemptuous of
freedom as the root of progress here as everywhere else, I view diversification as progress. There is some truth in the view that libertarian cliques get things started, but their goal only becomes a movement when the socialist masses finally join in with a clamor of
"you must," "we should," and "there ought to be a law!"It is usually the case that you will see sentences containing "should" and "we" in this way when you're being sold up the river. There exists some group of people who think you should live your life a certain way, regardless of your opinions on the matter, and this is a little of the manner in which they build up a rhetoric to justify their eventual use of force and constraint of law. Assumptions of inclusion and unity via "we" and assumptions of authority via "should." Neither are true; you're not a member of their little group unless you choose to be, and there is no authority beyond that which you grant them of your own choice.Here's the social science paper that prompted this line of discussion:
The Normative Dimensions of Extending the Human Lifespan by Age-Related Biomedical Innovations:
The current normative debate on age-related biomedical innovations and the extension of the human lifespan has important shortcomings. Mainly, the complexity of the different normative dimensions relevant for ethical and/or juridicial norms is not fully developed and the normative quality of teleological and deontological arguments is not properly distinguished. This article addresses some of these shortcomings and develops the outline of a more comprehensive normative framework covering all relevant dimensions. Such a frame necessarily has to include conceptions of a good life on the individual and societal levels. Furthermore, as a third dimension, a model for the access to and the just distribution of age-related biomedical innovations and technologies extending the human lifespan will be developed. It is argued that such a model has to include the different levels of the general philosophical theories of distributive justice, including social rights and theories of just health care. Furthermore, it has to show how these theories can be applied to the problem area of aging and extending the human lifespan.
It is unfortunate that human cultures seem so hardwired for inefficiency and waste - so much time spent on trying to justify coercion of others to attain your personally favored goals. Human nature is what it is, for now at least: best to keep plugging away at the problems you care about and do your best to hold up a decent set of standards by persuading rather than coercing.
Even if we could draft the masses to work to defeat aging, we should not do it; that would make us no better than those deathists who would set the agency of government to block research and mandate age-related death to their schedule.
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10.25.08
Posted in Uncategorized at 11:12 am by heaven
The human body is not a homogeneous mass, but rather a networked collection of very different structures and systems. Unsurprisingly, then, aging affects different tissues at different rates. This is just the same as in any engine, simple or complex: some components tend to fail due to accumulated damage more rapidly than others.
For example:
The 80-year-old Norwegian received a cornea transplant fifty years ago, a piece of tissue now 123 years old that still works today. It could be the oldest eye, or even human body part, still functioning or to have ever been in use for so long. ... He had a cornea transplanted into his right eye in 1958, from a man born in June 1885. At the time it was expected to work for only 5 years. However, Reuters report that the procedure has been in use since the early 20th century. That means there could be even older corneas out there.There is no profound lesson to be learned here, but this another useful example to present to people unfamiliar with the bounds of life span and survival in the natural world. If tortoises, whales, and this cornea can all manage such lengthy survival, it encourages the belief that medical research can engineer the same for human life in general. It is easier for people to accept that a goal can be accomplished based upon the evidence of a near example already in existence than in the absence of any example at all.
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