Longevity Meme Newsletter, August 10 2009

August 10 2009

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.



- Laser Ablation Funding Deadline on the 17th
- Wired on the Longevity Dividend
- Tooth Regeneration Coming Along Nicely
- Mutated Mitochondrial DNA and Aging
- Discussion
- Latest Healthy Life Extension Headlines


You'll recall I mentioned the Immortality Insitute fundraising effort for laser ablation of lipofuscin, an affordable research project to validate whether carefully tuned laser light can safely break down the damaging byproducts of metabolism that build up in our cells. Fundraising for this matching grant has a deadline of the 17th of this month - so if you feel that this is a worthwhile project, now is the time to make a donation:


Read more about this initiative back in the Fight Aging! archives:



Wired recently examined the Longevity Dividend point of view:


"The Longevity Dividend is an argument developed by a group of gerontologists and aimed at regulators and politically-influenced funding groups. It deliberately steers clear of talking about extending life span, instead presenting increased funding for applied aging research as a form of investment that will greatly reduce later government medical program expenditures through reducing incidence of age-related disease. In that sense it is a form of compressed morbidity viewpoint, the theory that the period of life spent in age-related frailty and suffering from age-related disease can be compressed down without extending life span. This runs contrary to aging-as-damage theories, which instead state that any intervention that reduces the level of accumulated damage will tend to extend overall life span in addition to its other beneficial effects."


Groups attempting to regenerate hair and teeth are both near the forefront of tissue engineering. Given the lesser risks involved in human trials of this sort of work, I would not be surprised to see therapies become widely available prior to more vital uses of the underlying technology - such as regenerative nerves and hearts.


"The ultimate goal of regenerative therapy is to develop fully functioning bioengineered organs which work in cooperation with surrounding tissues to replace organs that were lost or damaged as a result of disease, injury, or aging. Here, we report a successful fully functioning tooth replacement in an adult mouse achieved through the transplantation of bioengineered tooth germ into the alveolar bone in the lost tooth region. We propose this technology as a model for future organ replacement therapies."


Researchers continue to generate new information about the state of our mitochondria, the cell's power plants, and how it influences the pace of aging. This field is in the outright contraction phase, in which new data often conflicts or cannot all fit into one theory. Those of you who follow science will know that a few years of this usually precedes important new breakthroughs in understanding.


"That one group of researchers has point-mutation-bearing mice that age normally and another group has point-mutation-bearing mice that age faster indicates that there's more to this story, however. Something is unknown, always the case when solid research appears to be contradictory, and more research is needed to get to the bottom of the mechanisms here. But note that we could sidestep all of these issues with a technology that repairs or replaces mitochondrial DNA globally throughout the body - such as protofection, demonstrated back in 2005. If we replace all mitochondrial DNA with fresh new mitochondrial DNA, then it doesn't matter why or how its prior state was causing issues because we just fixed the problem.

"This is as good an example as any to show that we don't need complete understanding of human biochemistry in order to make important inroads into repairing the damage of aging. More understanding helps, but we have enough knowledge now to move ahead with significant and important rejuvenation technologies - were there a large research community and the will and funding to forge ahead. But here, as in so many nascent fields of biotechnology with great potential, we are left lacking. There is no large research community focused on replacing mitochondrial DNA, and to the best of my knowledge only a few small groups are presently working on this sort of technology."


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!




In the near future it will be possible to increase the rate at which new neurons and neural connections are created in the brain. This looks promising as a way to tackle some aspects of age-related decline: "Newborn neurons are continuously produced in the hippocampus, which may be involved in several cognitive functions, including learning and memory, throughout life. However, both hippocampus-dependent cognitive functions and the level of adult neurogenesis are gradually attenuated as aging progresses. Few studies have explored the relationship between adult neurogenesis and cognitive functions, especially in primates. In this study, we evaluated learning performance and hippocampal neurogenesis utilizing young and aged cynomolgus monkeys. Significant attenuations in learning performance and adult neurogenesis were detected in aged monkeys. Interestingly, there was a positive correlation between learning performance and the level of neurogenesis. Our findings suggest that cognitive functions and adult neurogenesis may have some interdependent relationships during aging."

The immune system declines and malfunctions with age, but researchers are making strides towards methods of reprogramming that might restore an age-damaged immune system to better operation: researchers have "identified a protein that could serve as a target for reprogramming immune system cells exhausted by exposure to chronic viral infection into more effective "soldiers" against certain viruses like HIV, hepatitis C, and hepatitis B, as well as some cancers, such as melanoma. ... the protein Blimp-1 (B-lymphocyte-induced maturation protein 1) represses the normal differentiation of CD8 T cells into memory T cells, which recognize disease-causing agents from previous infections and enable the body to mount faster, stronger immune responses. The team also reports that Blimp-1 causes exhausted CD8 T cells to express inhibitory receptors, which prevent recognition of specific antigens, further weakening immune response. The researchers describe how complete deletion of Blimp-1, which is overexpressed in CD8 T cells during chronic viral infection, reversed these aspects of T cell exhaustion." Note that one important cause of immune system aging is chronic infection by cytomegalovirus - this work probably has relevance to aging.

A snapshot of ongoing work to develop cost-effective tools for building targeted cancer therapies: "Scientists have spent more than a decade trying to direct liposomes to specific cancer cells, with limited success. A common approach involves attaching an antibody to the liposome membrane. Ideally the antibody will bind to a cancer cell receptor so that it can deliver the liposome - and the cancer drug - into the cell. Developing such antibodies is costly and time-consuming, however, and the process of attaching them to liposomes is difficult to control. ... Aptamers are short strands of DNA or RNA; they are highly efficient binders, and are very easy to make, label and manipulate ... [researchers] used an aptamer that binds to nucleolin receptors, which are found in abundance on certain breast cancer cells. The researchers then developed an effective method for attaching the aptamer to a liposome loaded with cisplatin, a drug that effectively kills cancer cells but has troublesome side effects when administered intravenously. Tests in cells grown in the lab yielded promising results. Four days after they exposed the cells to the new drug-delivery system, 59.5 percent of the breast cancer cells had died, while less than 12 percent of breast cancer cells treated with cisplatin alone had died. ... Another advantage of using aptamers as targeting agents is that they are easily disabled. They readily bind to complementary DNA, which prevents them from interacting with cell receptors."

Here, Chemical & Engineering News looks at the practice of calorie restriction: "lthough Paul McGlothin and Meredith Averill are in their early 60s, the married couple from New York State says that they feel at least 20 years younger. This is no idle claim: Their blood pressures, resting heart rates, and body fat percentages rival those of Olympic athletes. ... So what's their antiaging secret? For the past 16 years, McGlothin and Averill have been eating a carefully controlled, calorie-restricted diet. ... Scientists have known for decades that caloric restriction - reducing calorie intake without malnutrition - slows aging and extends life span in model organisms ranging from yeast to mice. Exactly why and how it confers these benefits in animals, and whether similar effects could be attained in humans, have been a mystery. ... Caloric restriction is about more than just being thin and fit. Something about eating a diet that is low in calories but nutritionally complete causes a dramatic reprogramming of cellular metabolism that can't be replicated by exercise or by eating smaller amounts of high-calorie foods. In laboratory animals such as fruit flies, roundworms, and mice, caloric restriction switches biochemical pathways on or off, resulting in higher insulin sensitivity, decreased inflammation, enhanced cardiovascular functioning, reduced muscle wasting with age, and improved resistance to cellular stress. Not only is normal aging slowed, but calorie-restricted animals are also less likely to develop age-associated diseases such as diabetes and cancer."

Not all of the cells in your body replace their populations on a regular basis. Some groups of cells will last almost an entire lifetime, and across that lifetime they will become increasingly damaged and dysfunctional. Here is an overview of that process: "It is now generally accepted that aging and eventual death of multicellular organisms is to a large extent related to macromolecular damage by mitochondrially produced reactive oxygen species, mostly affecting long-lived postmitotic cells, such as neurons and cardiac myocytes. ... The inherent inability of autophagy and other cellular degradation mechanisms to completely remove damaged structures results in the progressive accumulation of garbage, including cytosolic protein aggregates, defective mitochondria and lipofuscin - an intralysosomal indigestible material. ... The slow accumulation of lipofuscin within lysosomes seems to depress autophagy, resulting in reduced mitochondrial turnover. The latter are not only functionally deficient but also produce increased amounts of reactive oxygen species, prompting [the creation of lipofuscin]. Moreover, defective and enlarged mitochondria are [only poorly recycled] and constitute a growing population of badly functioning organelles ... The progress of these changes seems to result in enhanced oxidative stress, decreased ATP production, and collapse of the cellular catabolic machinery, which eventually is incompatible with survival." This is the garbage catastrophe of the cell: garbage builds up, which makes things worse and leads to more garbage. Eventually it kills the cell, and enough of this will kill you too.

I don't think I've pointed out the Healthy Life Extension Society, or Heales before; it's a group based in Belgium, and so you'll find more French and Dutch content than English material at the Society's website. For the rest of us English-speaking monolinguists, there's always Google Translate: "Each day 100,000 people die due to the effects of old age. Aging is responsible for 90% of deaths in the richest countries and two-thirds of deaths in the world. It doesn't just cause innumerable deaths, it is also the source of horrible suffering - Alzheimer's Disease, muscular atrophy, damage to vision and hearing, osteoporosis, rheumatoid arthritis ... The only way to prevent these illnesses linked to aging is to attack the root cause – that is aging itself. It is time to start working towards solutions to this universal human tragedy. Heales raises awareness of new developments in the area of biogerontolgy (the science of aging). We promote and support anti-aging research." As I noted in the latest Longevity Meme newsletter, Heales is holding a fundraising music festival for LysoSENS research next month.

Your thymus is the source of T-cells, the varied workers of the immune system. As you age, the thymus involutes - degenerates - and production of new T-cells fades away. Calorie restriction (CR) slows this process, which is no doubt one of the ways in which it improves immune response: "Aging of thymus is characterized by reduction in naive T cell output together with progressive replacement of lymphostromal thymic zones with adipocytes. Determining how calorie restriction (CR), a prolongevity metabolic intervention, regulates thymic aging may allow identification of relevant mechanisms to prevent immunosenescence. Using a mouse model of chronic CR, we found that a reduction in age-related thymic adipogenic mechanism is coupled with maintenance of thymic function. The CR increased cellular density in the thymic cortex and medulla and preserved the epithelial signatures." The paper then goes into some detail as to the controlling biochemical mechanisms and gene expression that accompanies these changes.

Investigating cancer stem cells may uncover useful targets for new selective cell destruction methods, such as this one: researchers "have identified the first human bladder cancer stem cell and revealed how it works to escape the body's natural defenses. ... [the gene] CD47 works to prevent leukemia cells from being engulfed by macrophages by binding to a molecule on the surface of the macrophage. Blocking this interaction with an antibody specific for CD47 allows the macrophages to swallow the leukemia cells. When [researchers] tried a similar experiment with the bladder cancer stem cells in a test tube, the same thing happened - human macrophages began to destroy the cancer cells. ... Leukemia is totally different from the kind of epithelial cancer we see in the bladder, so it was very exciting to see that these two kinds of cancer stem cells use a similar mechanism to escape the macrophages. ... The researchers are now investigating whether CD47 is expressed at high levels on other cancer stem cells and pondering ways to help circulating macrophages better infiltrate solid tumors - always with an eye towards therapy."

Another example of calorie restriction improving immune system performance, this time in humans rather than other primates: "Calorie restriction (CR) enhances immune response and prolongs life span in animals. However, information on the applicability of these results to humans is limited. T-cell function declines with age. We examined effects of CR on T-cell function in humans. Forty-six overweight, nonobese participants aged 20–42 years were randomly assigned to 30% or 10% CR group for 6 months. Delayed-type hypersensitivity (DTH), T-cell proliferation (TP), and prostaglandin E2 (PGE2) productions were determined before and after CR. DTH and TP to T-cell mitogens were increased in both groups over baseline. However, number of positive responses to DTH antigens and TP to anti-CD3 reached statistical significance only after 30% CR. Lipopolysaccharide-stimulated PGE2 was reduced in both groups but reached statistical significance after 30% CR. These results, for the first time, show that 6-month CR in humans improves T-cell function." Mild CR provides only mild benefits, as we would expect.

Here is an example of how looking at observable data on aging - such as mortality rates - can inform us of the nature of underlying mechanisms of aging: "What do you think are the odds that you will die during the next year? Try to put a number to it - 1 in 100? 1 in 10,000? Whatever it is, it will be twice as large 8 years from now. This startling fact was first noticed by the British actuary Benjamin Gompertz in 1825 and is now called the 'Gompertz Law of human mortality.' Your probability of dying during a given year doubles every 8 years. For me, a 25-year-old American, the probability of dying during the next year is a fairly miniscule 0.03% - about 1 in 3,000. When I'm 33 it will be about 1 in 1,500, when I'm 42 it will be about 1 in 750, and so on. By the time I reach age 100 (and I do plan on it) the probability of living to 101 will only be about 50%. This is seriously fast growth - my mortality rate is increasing exponentially with age. ... There is one important lesson, however, to be learned from Benjamin Gompertz's mysterious observation. By looking at theories of human mortality that are clearly wrong, we can deduce that our fast-rising mortality is not the result of a dangerous environment, but of a body that has a built-in expiration date." You might also look at the reliability theory of aging for a similar process of insight.



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