Longevity Meme Newsletter, December 08 2008

December 08 2008

The Longevity Meme Newsletter is a weekly e-mail containing news, opinions and happenings for people interested in healthy life extension: making use of diet, lifestyle choices, technology and proven medical advances to live healthy, longer lives.



- Presentations from Understanding Aging
- A Glance at the State of Stem Cell Research
- Discussion
- Latest Healthy Life Extension Headlines


Jeriaska of Future Current has posted three presentations from the Understanding Aging conference earlier this year. Links, excerpts, and comments can be found in the following Fight Aging! posts:


"Lipofuscin is this aggregate of oxidized lipids and proteins that [we] think is the problem. We think lipofuscin is sufficient to knock down autophagy as it accumulates. Eventually you get cells that are loaded with lipofuscin and the lysosomes cannot do their job of rejuvenating the cell. We think many aspects of aging are the result. If that is true, this is where the whole idea of "removing the garbage" comes in. We think the garbage itself is the problem, and if you can get rid of it we can make some serious inroads into conquering aging."

Those presenters believe it should be possible to use pulsed lasers to break up lipofuscin compounds without damaging cells - a very intriguing idea. Another of the presentations looks at Sierra Sciences and their research into the telomere biochemistry of aging and cancer:


"Sierra Sciences has been in existence for about nine years. We have worked really hard trying to figure out all we can about telomerase. ... We now have a 300,000 compound library and are searching for compounds that will turn on telomerase."

This branch of aging research is newly interesting to me because of recently discovered associations between age-related telomere shortening, telomerase, and mitochondrial damage. It seems plausible at this stage that these three things are all facets of a single process of accumulating damage to mitochondrial DNA and reactions to that damage in other parts of the cell. See the following Fight Aging! post for more on that topic:



Where is the scientific community in terms of progress towards the promise of stem cell therapies? A list of published research funded by the California Institute for Regenerative Medicine is one way of taking in the landscape at a glance:


"Our stem cells are complex machinery; in between the scientific successes that have immediate application, much of present research is the biochemical equivalent of tracing wires and dismantling clockwork to understand how it works. The pace of basic research is fast, however, and the field is comparatively well funded. Ten years from now, I would not be at all surprised to see the research community to possess a fairly complete picture of the biochemistry of stem cells: how they work, and what signals and genes control each step of the processes that take place inside our bodies. From there on in, it's all application of that knowledge."


The highlights and headlines from the past week follow below.

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To view commentary on the latest news headlines complete with links and references, please visit the daily news section of the Longevity Meme: http://www.longevitymeme.org/news/

The Life Expectancy Puzzle of Left-Handedness (December 05 2008)
Many identified differences in human longevity between groups lack conclusive explanations, such as why women have a greater life expectancy. Differences in life expectancy due to handedness are another puzzle: "Many studies report that left-handers have a shorter longevity than right-handers, and the present study may provide a possible explanation for that finding. In a Cardiac Rehabilitation Unit for the elderly with a mean age of 75.2 years the prevalence of left-handers was 16.7%. This latter value was significantly different from the 6.7% in controls of similar age. These data suggest that heart disease may be one reason for a reduced longevity among left-handers. Left-handers use the right hemisphere for movement, and unilateral activation of that hemisphere in the form of EEG desynchronization and deactivation in the form of EEG slow waves are both related to cardiac abnormalities." In the grand scheme of things these differences are unimportant: the greatest determinant of our future longevity is progress in the application of aging research.

On Immunosenescence (December 05 2008)
Researchers discuss the failing, age-damaged immune system: "At present, individuals can live up to 80-120 years, a time much longer than that of our ancestors, as a consequence of the improvements in life conditions and medical care. Thus, the human immune system has to cope with a lifelong and evolutionarily unpredicted exposure to a variety of antigens, which are at the basis of profound age-related changes globally indicated as immunosenescence, a multifaceted phenomenon that increases morbidity and mortality due to infections and age-related pathologies. The major changes occurring during immunosenescence are the result of the accumulation of cellular, molecular defects and involutive phenomena (such as thymic involution) occurring concomitantly to a hyperstimulation of both innate and adaptive immunity (accumulation of expanded clones of memory and effector T cells, shrinkage of the T cell receptor repertoire, progressive activation of macrophages), and resulting in a low-grade, chronic state of inflammation defined as inflammaging. It is unknown whether inflammaging, which represents a risk factor for most age-related pathologies, is a cause or rather an effect of the aging process. ... centenarians seem to be equipped with gene variants that allow them to optimize the balance between pro- and anti-inflammatory molecules, and thus to minimize the effects of the lifelong exposure to environmental insults and stressors."

Dormant Emergency Stem Cells (December 04 2008)
An intriguing discovery from a cancer research group that I suspect has more promise for the field of regenerative medicine: "Up to now, scientists have assumed that adult stem cells have a low division rate. According to theory, they thus protect their DNA from mutations ... [Researchers] have now discovered a group of stem cells in mouse bone marrow that remain in a kind of dormancy [and] divide only about five times throughout the life of a mouse. Translated to humans, this would correspond to only one cell division in 18 years. ... In contrast, stem cells of the larger group, the 'active' stem cells, divide continuously about once a month. However, in an emergency such as an injury of the bone marrow or if the messenger substance G-CSF is released, the dormant cell population awakes. Once awakened, it shows the highest potential for self-renewal ever to be observed in stem cells. If transplanted into irradiated mice, these cells replace the destroyed bone marrow and restore the whole [blood] system. It is possible to isolate new dormant stem cells from the transplanted animals and these cells are able to replace bone marrow again – this can be done several times in a row. The situation is different with 'active' stem cells, where bone marrow replacement can successfully be carried out only once."

Call for Submissions for Hourglass VI (December 04 2008)
Your submissions are wanted for the sixth Hourglass blog carnival on aging and longevity science: "Topics of posts should have something to do with the biology of aging, broadly speaking - including fundamental research in biogerontology, age-related disease, ideas about life extension technologies, your personal experience with calorie restriction, maybe even something about the sociological implications of increased longevity. Opinions expressed are not necessarily those of the management, so feel free to subvert the dominant paradigm. If in doubt, submit anyway. ... In the meantime, feel free to check out previous editions of the carnival. By the way, if you'd like to volunteer to host, please email me directly - basically all of 2009 is wide open. If you've already hosted before, don't let that hold you back; while the carnival is young, some repeat hosting is going to be par for the course."

Evidence Against the Cancer Stem Cell Theory (December 03 2008)
It would be good for all of us if the cancer stem cell theory turns out to be true for even a majority of cancer types - as this would mean that a side-effect of stem cell research will be a cure for cancer. Unfortunately, there are good reasons to believe that this will not be the case; nothing in human biochemistry is as simple as we'd like. From EurekAlert!: "the cancer stem-cell model [must] be reassessed because it is based largely on evidence from a laboratory test that is surprisingly flawed when applied to some cancers ... I think the cancer stem-cell model will, in the end, hold up for some cancers. But other cancers, like melanoma, probably won't follow a cancer stem-cell model at all. ... Scientists previously estimated that only one in 1 million melanoma cells has the ability to run wild, exhibiting the kind of unchecked proliferation that leads to new tumors. These aggressive interlopers are the cancer stem cells, according to backers of the model. But after updating and improving the laboratory tests used to detect these aberrant cells, [researchers] determined that at least one-quarter of melanoma cells [have] the ability to form new tumors. ... The assay on which the field is based misses most of the cancer cells that can proliferate to form tumors. Our data suggest that it's not going to be possible to cure melanoma by targeting a small sub-population of cells."

Senescent Cells and Cancer (December 03 2008)
One of the consequences of an aging immune system is that it stops removing senescent cells - certainly, senescent cells increase dramatically with age. Here is a look at why that process is likely to increase your cancer risk: "Although 'cellular senescence' can suppress tumor formation from damaged cells by blocking the cell division that underlies cancer growth, it has also been implicated in promoting cancer and other age-related diseases. To understand how this might happen, we measured proteins that senescent human cells secrete into their local environment and found many factors associated with inflammation and cancer development. ... Senescent cells promote the growth and aggressiveness of nearby precancerous or cancer cells ... Our findings support the idea that cellular senescence can be both beneficial, in preventing damaged cells from dividing, and deleterious, by having effects on neighboring cells; this balance of effects is predicted by an evolutionary theory of aging." Senescent cells are a prime target for the same sorts of discerning therapies being developed to kill cancer cells with no side-effects.

Alcor Now Accepts Donations Online (December 02 2008)
Given that the end of the year is approaching, and I just recently discussed my plans for a year-end charitable donation to the Methuselah Foundation over at Fight Aging!, I should note that Alcor now accepts donations online: "We now have the ability to accept charitable donations through our website. Alcor has a long, proud tradition of innovation and technical excellence in the field of cryonics. Without the charitable gifts from our members and supporters, the organization would be unable to prosper. A first draft budget has been completed for next year and the organization is likely to face a large deficit in 2009. Your gift will help sustain the general operations budget at the level necessary to continue in our quest for better cryopreservations. Your decision to donate is sincerely appreciated. Remember your donation is tax deductible."

Towards Tuning the Immune System (December 02 2008)
Researchers are making good progress towards control over immune cells, and future goals seems likely to be applicable to the restoration of some function to an age-damaged immune system. Researchers have identified "seven different receptors on T cells that can tamp down immune responses during a prolonged battle with an infectious pathogen or against developing cancer. Chronic over-stimulation of the immune system can lead to poor control of infections and cancer, so the results explain why it is that these key immune cells gradually become 'exhausted' and ineffective over time
. ... We are starting to see a picture emerging of a really tuneable array of inhibitory receptors expressed on T cells. That suggests it may be possible to not only dramatically enhance antiviral or antitumor T cell responses, but also to fine tune which response you want to enhance in order to reverse T cell exhaustion and continue fighting an infection or disease. This presents us with a great clinical opportunity. T cells have a lot of weapons at their disposal to control viral infection and most of them are disarmed when these cells become exhausted. It may be possible to selectively rearm T cells while generally reinvigorating them."

Works in Mice, Not in Worms (December 01 2008)
The BBC provides a good example of the press running with the wrong conclusion due to insufficient knowledge of the field: researchers "genetically manipulated nematodes so that their bodies were able to 'mop up' surplus free radicals. This, in theory, should give them an advantage over normal nematodes in terms of ageing and lifespan. However, these worms lived just as long as the others, suggesting that 'oxidative stress' is less of a factor in the ageing of our cells and tissues as some have suggested." Except of course that a similar process performed in mice - genetic engineering to produce more natural antioxidants targeted to the mitochondria - does extend longevity. This may be another case of it being important as to exactly how you engineer extra antioxidant chemicals in the body, or it may be that the biochemistry of nematodes is unusual in not responding to more natural antioxidants. All in all, it's a little early to be declaring the death of oxidative damage as an important part of aging.

More On Exercise and the Aging Brain (December 01 2008)
It's well worth remembering that regular exercise brings benefits that no present medical technology can match-and at a fraction of the cost of medicines that do far less. EurekAlert! notes that researchers compared "brain scans of older adults who exercise to brain scans of those who do not. ... The researchers recruited 12 healthy adults, age 60 to 76. Six of the adults had participated in aerobic exercise for three or more hours per week over the last 10 years, and six exercised less than one hour per week. All of the volunteers underwent MRI to determine cerebral blood flow and MR angiography to depict blood vessels in the brain. ... researchers were able to make 3-D models of the blood vessels and examine them for shape and size. They then compared the blood vessel characteristics and how they related to blood flow in both the active and inactive groups. The results showed that the inactive group exhibited fewer small blood vessels in the brain, along with more unpredictable blood flow through the brain. ... The active adults had more small blood vessels and improved cerebral blood flow. These findings further point out the importance of regular exercise to healthy aging."



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