Longevity Meme Newsletter, March 30 2009

March 30 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.



- Popular Media and Discussion of Longevity
- Dreams of Molecular Nanotechnology
- Discussion
- Latest Healthy Life Extension Headlines


Given the incentives placed upon producers of popular media, no-one should expect accuracy. Urges to accuracy take second place to the need to say and do whatever will best compete for attention. So to Oprah's recent examination of the practice of calorie restriction for its considerable health benefits and possible longevity benefits:


"There's a style to this sort of thing, in which the presenters construct a framework for their article or show that ostensibly bears some semblance to the underlying reality under discussion, but within which a majority of the 'facts' provided are simply wrong, chosen for their ability to grasp attention rather than any scientific backing they may have.

"Hence for a discussion of longevity, wild and unsupported claims are fair game. At the present time, the scientific consensus is that human practice of calorie restriction will not greatly enhance maximum longevity, but does greatly improve health and greatly reduce risk of age-related disease. That isn't as exciting, however, as earlier speculation on attaining 120 year or more life spans, so the more exciting 'fact' is what gets aired."

To be clear: there is nothing a healthy person can presently do that is better for long-term health than the practice of calorie restriction plus regular exercise. No drug, supplement, or other lifestyle even comes close - and there exists plenty of scientific evidence from human studies to back up that statement. The difference between doing this and not doing this is plausibly a decade or two of healthy life, and major diseases of aging avoided.

This is to say that you have a lot of control over your personal longevity, and where it falls in the present human range. Live well and you'll most likely live longer. Do you want to be crippled by age-related disease at 70, or up for tennis at 80? That's in your hands.

However, claims of large extensions to maximum human life span through the practice of calorie restriction are not supported by the present scientific consensus. Humans aren't mice, and there's only so far you can take the amazing results of calorie restriction experiments in lower mammals. Dreams of 120 year life spans for large numbers of people through the practice of calorie restriction alone are just that: dreams.

The only way we're all going to make it to 120 in good shape is by supporting rapid progress in cutting edge medical technology, such as the research funded by the Methuselah Foundation aimed at repairing and reversing the known cellular damage of aging:



While our society is still only at the very base of the ladder of longevity technologies, we have a good view ahead as to what is possible in years to come. We know that we or our descendants can eventually cure aging completely, because we know that the machinery capable of that task is not forbidden by the laws of physics - and in fact many good examples already exist in the world around us.


"There's no law of physics that will prevent we clever humans - and our enhanced descendants - from eventually building technologies that can maintain and arrange every aspect of our bodies exactly as we'd like them to be. Technologies that can find every out of place molecule or damaged component and promptly fix it up. Aging will be a thing of the past in that era of molecular nanotechnology, whenever it comes to pass.

"Systems that can identify, manage and place trillions of molecules accurately are not a pipe dream; after all, we are already surrounded by examples. You, for example, are just such a system, albeit somewhat slow at self-assembly to full size. There's nothing in the laws of physics that jumps out and says we can't do this. It's just a matter of time.

"Our cells are already very impressive examples of adaptive machinery. The machines our descendants will build with the knowledge gained from today's study of biology will be even more impressive yet. Cells, for all their intricacy, are far less efficient and organized than the laws of physics permit. One day, that inefficiency and disorganization will be eliminated by machinery intended to augment or replace our cells, and everyone will be the better for it."


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!




Heat Shock Proteins and Cancer Immunotherapy (March 27 2009)
One of the roles of heat shock proteins such as Hsp70 is to carry other proteins around a cell - for example, when they are damaged or misplaced and need to be broken down in a lysosome. This paper shows that if you hook out heat shock proteins from cancer cells, they come attached to all sorts of biochemicals that can be used to train the immune system to kill those cancer cells: "In the present investigation, we have demonstrated that immunization with tumor cell derived Hsp70 lead to an effective survival advantage in mice with minimal residual tumor cells from which Hsp70 is derived, by involvement of immune cell types in the rejection of tumors ... It has been observed that autologous Hsp70 induces specific anti-tumor immunity and effectively eradicates tumors in the host mice, thereby enhancing survival of tumor-bearing host. ... Furthermore, Hsp70 immunized mice did not show any systemic disorder. Therefore, it could be assumed as safe and might be clinically useful for vaccination against malignant human tumors."

Improved Induced Pluripotency (March 27 2009)
Researchers continue to move rapidly in advancing the state of the art in induced pluripotent stem cells: "A team of scientists has advanced stem cell research by finding a way to endow human skin cells with embryonic stem cell-like properties without inserting potentially problematic new genes into their DNA. ... This is not the first time that scientists have endowed differentiated cells like skin cells with the capacity to develop into any of the roughly 220 types of cells in the body, a process known as induced pluripotency. But it is the first time that they have done so without using viruses, which can insert potentially harmful genes into the cells' genetic material and trigger cancer. [The] new method imports the necessary genes on a small circle of DNA known as a plasmid. Over time, the plasmid disappears naturally from the cell population, avoiding the danger posed by using viruses. Scientists view pluripotent cells as invaluable to studies of normal and disease processes and to understanding the effects of certain drugs. In the future, doctors might be able to use such cells therapeutically to replace those affected by diseases such as Alzheimer's and Parkinson's or lost to traumatic injuries."

More on the Value of Exercise (March 26 2009)
Level of exercise beginning in middle age and mortality rate are very well correlated, as shown by this study: "Despite the known hazards of physical inactivity, it continues to be a major health problem. Physical inactivity is associated with increased incidence rates of obesity, diabetes, cardiovascular diseases, osteoporosis, and cancer ... The absolute mortality rate was 27.1, 23.6, and 18.4 per 1000 person years in the groups with low, medium, and high physical activity, respectively. The relative rate reduction attributable to high physical activity was 32% for low and 22% for medium physical activity. ... Increased physical activity in middle age is eventually followed by a reduction in mortality to the same level as seen among men with constantly high physical activity. This reduction is comparable with that associated with smoking cessation." To restate that last point: lazing around and skipping over a little exercise every day costs you as much healthy life in the long run as smoking does.

Immunized Against Cancer? (March 26 2009)
From ScienceDaily: "New research suggests that monoclonal antibody therapy of cancer can be improved to be much more powerful than it is today ... We believe that antibody therapy has the capacity to immunize people against cancer. Treatment modifications might be able to prolong, amplify, and shape a continuous immune response to cancer cells ... Scientists now believe that it will be possible to alter the antibodies so that they induce both kinds of human immunity - the innate immune response that is short-lasting and which directly kills tumor cells, and a long-lasting 'memory' response that comes from the adaptive immune response. ... We have long thought that monoclonal antibodies are capable of stimulating the innate immune system, but we now have evidence that the therapy can prime an adaptive response as well. Such responses would make the treatment much more powerful, capable of keeping cancer under control."

Autophagy and Neurodegeneration (March 25 2009)
Autophagy, the process of recycling cellular components, is known to be important to the benefits of calorie restriction. This makes sense: more recycling of damaged components should mean they have less of a chance to cause additional damage due to their malfunctioning. Calorie restriction is known to slow onset of neurodegenerative conditions, and this also may have something to do with autophagy: "Protein aggregates or inclusion bodies are common hallmarks of age-related neurodegenerative disorders. ... Increasing evidence, [supports] the notion that in general aggregates confer toxicity and disturb neuronal function by hampering axonal transport, synaptic integrity, transcriptional regulation, and mitochondrial function. Thus, neuroscientists in search of effective treatments to slow neural loss during neurodegeneration have long been interested in finding new ways to clear inclusion bodies. Intriguingly, two studies [indicate] that autophagy may be a built-in defense mechanism to clear the nervous system of inclusion bodies. This new finding has implications for our understanding of aging and neurodegeneration and the development of new therapies."

Old Cells (March 25 2009)
The HHMI Bulletin looks at cellular senescence. There's a PDF version for those who don't want to click through six pages to read the whole thing: "cells might not sprout gray hair, get achy joints, or forget where they put their car keys, but they do age. ... researchers are just beginning to learn what happens to cells as they grow old, and they're making connections between those changes and cancer, deficiencies in wound healing, and other problems that increase in likelihood as a person ages. ... In a sense, cancer and senescence are opposite sides of the same coin. To remain robust, tissues rely on dividing cells for replenishment; yet, left unchecked, cell division leads to cancer. Thus, it might seem a Faustian bargain to guard against cancer now at the expense of decrepit tissues later. ... senescent cells produce an enzyme called beta galactosidase. When bathed in a particular sugar compound, cells with this enzyme turn blue, providing a way to spot senescent cells. Since then, researchers have used this method to show that tissues from people, as well as from animals such as rodents and monkeys, carried blue cells. And, 'the older you got the more blue cells you had.'"

On Longevity Gene Networks (March 24 2009)
Our genes of metabolism interact in a very complex and dynamic fashion, and some aspects of that interaction determine longevity. Efforts to pick apart this tangled web require equally complex tools of analysis: "The genome era and the advent of high-throughput technologies have brought about a huge increase in the amount of data available to biologists: each genome contains tens of thousands of genes, whose products can potentially interact with each other in an astronomical number of ways. This quantitative change has created a need for a qualitative change in the way we perform analyses: the human brain is not very good at understanding thousands of things at once, let alone millions or billions, so we must find new ways to extract comprehensible patterns from torrents of data. Many of the techniques being developed to analyze large biological networks fall under the umbrella of systems biology. Some of the newest tools have been used guide genetic perturbation studies in yeast, resulting in the discovery of novel lifespan control genes. What can such network analysis tell us about human aging?" The enormous complexity of metabolism-determined longevity is yet another argument for focusing on repair of already identified damage to reverse aging, rather than trying to manipulate this tangled system to slow aging.

What is Transhumanism? (March 24 2009)
Via the Exception: "The doubling rate of medical knowledge is three years - that is, the next three years of medical research will yield as much knowledge as has been yielded in all of human history. The next three years will double our knowledge again, and again, and so on. This exponential growth in knowledge will rapidly enable us to eradicate disease and radically improve the human condition. Indeed, we will be able to look beyond curing the sick, towards a future in which we make ourselves more than healthy. We will be able to enhance our memory and our intellectual capacity. We will use technology to make ourselves faster, more efficient, and radically longer-lived. We will be able to augment our physical strength, stamina, and resistance to disease. We might enhance specific skills, such as visual acuity or musical talent. In the extreme, we will correct the molecular wear-and-tear that causes deterioration and death – reversing the aging process itself. Humans might even obtain entirely new capacities, such as infrared vision, or bat-like echolocation. The body of thought that deals with enhancement technologies is called transhumanism. In essence, transhumanists favor using technology to enhance mental and physical human capacities."

Bivalves in Aging Research (March 23 2009)
You might recall that some species of clam live for as long as four centuries, and possibly longer. Others do not. Such differences between closely related species are an opportunity for researchers to uncover important mechanisms of longevity. From Ouroboros: "This invertebrate group includes species with the longest metazoan lifespan approaching 400 y, as well as species of swimming and sessile lifestyles that live just for 1 y. Bivalves from natural populations can be aged by shell growth bands formed at regular intervals of time. ... Extreme longevity of some bivalve models may help to analyze general metabolic strategies thought to be life prolonging, like the transient depression of metabolism, which forms part of natural behaviour in these species. ... One of the great advantages of bivalves is their variety: even though they're anatomically quite similar, they occupy a wide range of niches and consequently exhibit a large variation in aspects of their natural histories, including longevity. This makes clams and oysters excellent candidates for comparative biogerontology: studying organisms with basically identical body plans but wildly different lifespans allows us to focus more tightly on the features (molecular, cellular, systemic) that might explain the change in longevity. This theme is currently being developed - outside the mollusk community - into a large-scale project that will study dozens of species in four or five vertebrate clades."

Hyping Resveratrol (March 23 2009)
I suspect that commercialization of resveratrol and other calorie restriction mimetics is going to reinforce an existing and undesirable view of longevity science - that it's all supplements and diet, that it's all slowing aging, that the "anti-aging" marketplace has legitimacy. This doesn't help generate support for serious attempts to repair the damage of aging and thus reverse aging - if the pill, supplement, and scam marketplace was going to help, we'd have seen some evidence of that already. But the contributions of the "anti-aging" marketplace (dietary supplements on one side and lies on the other) are largely distraction and disinformation: "The lure of eternal youth has produced a multibillion-dollar-a-year global marketplace full of potions and pills that, the manufacturers claim, can offer life-extending benefits. Amid the dizzying array, one substance is capturing prime time attention: resveratrol. Resveratrol advertisements - Reverse your biological clock! A miracle molecule! - are popping up everywhere, from the Internet to local health food stores. The stuff is even showing up in anti-wrinkle creams." Resveratrol doesn't even capture all the benefits of simply practicing calorie restriction, and slowing aging is a far worse outcome than reversing aging - the latter being a path that isn't any harder at this stage. Toiling to merely slow aging is the wrong, worse, and less helpful direction.



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