Longevity Meme Newsletter, January 18 2010

January 18 2010

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.



- A Project for 2010
- The Campaign Against Aging
- The Prospect of Cancer Does Not Worry Me
- Anticipating Early Longevity Drugs
- Discussion
- Latest Healthy Life Extension Headlines


As we inch our way into 2010, allow me to point out a worthwhile fundraising effort for longevity research undertaken by the SENS Foundation:


"Last year a few earnest folk started and publicized a Facebook Cause, a group pledge that aims to gather 10,000 members in support of the longevity research carried out by the SENS Foundation. This research aims to reverse critical biochemical changes that cause age-related degeneration, frailty, and disease, and thereby eliminate suffering and restore the aged to health. ... The cause asks each member to pledge just $100, which becomes payable once a total of 10,000 individuals have made the same pledge."

I am impressed to note that the Cause has already assembled more than 1600 pledges to donate $100, which I think shows that the stated goal of 10,000 supporters is viable and plausible. Achieving this end is well within the capabilities of our extended community - so give these folk a helping hand.


The Campaign Against Aging is a recently launched advocacy initiative for longevity science. I'm always pleased to see new faces and new endeavors taking place. Diversity and breadth of the pro-longevity community is vital for progress.


"We will be starting a major awareness raising campaign in February, lasting through February and perhaps March. This campaign will use 'feet on the ground' methods such as posting flyers, distributing business cards, speaking to groups of people, and so on. I'll provide more details as the plans solidify. The tentative goal is to reach about 5,000 to 20,000 people by these methods."


Cancer lies in each of our futures; the only people who have avoided cancer in the past were those struck down by some other cause beforehand. Cancer is less a disease and more an inevitable consequence of the way in which human biology works and is damaged through use. But the prospect of cancer does not concern me:


"I have perhaps two or three decades to go before I enter the high risk years for developing cancer. I am confident that by that time, very effective targeted cancer therapies with few side-effects will be widely available. Consider that:

"(1) Cancer research is perhaps the most highly funded and widely supported of any modern distributed medical development program.

"(2) Over the past five years, very impressive anti-cancer technology demonstrations have been made. These are a new breed of targeted therapy, built using the latest tools of modern biotechnology. Immune cells, viruses, or nanoparticles are engineered to home in on the distinctive surface chemistries of cancer cells - and then destroy them.

"(3) With a sufficiently good targeted therapy, even aggressive metastasis of cancer becomes a minor inconvenience. Those spreading cancer cells will still be found and killed, no matter where they are in the body."


That part of the longevity science research community working to slow down aging will introduce the first, only modestly beneficial, longevity-enhancing drugs not too many years from now. Given present medical regulation and the way in which the drug development community operates, what can be say about how that will happen?


"The case is made that the early years of drugs to slow aging will look something like the progression of statins. Bear in mind while reading that that the FDA does not consider aging to be a disease, and will therefore not approve any treatment for aging. Thus any potential longevity therapy is sidelined into development for one specific age-related disease very early on in its life, trials would focus on that narrow use only, and the therapy would only be authorized for that narrow use at the outset

"Back in 2008 the results of the JUPITER trial [for a statin] were published, and they showed that statins could reduce the incidence of major cardiovascular events in people with normal cholesterol levels. The FDA is considering permitting as many as 6 million people whose cholesterol levels fall within a normal range to take statins. ... I find the case of statins interesting to follow for I believe it foreshadows the challenges that await the first [longevity-enhancing] drug that will come to market in the not-too-distant future ... Such a drug will first be prescribed only for patients suffering a particular disease, like diabetes. But if this drug not only has a therapeutic benefit, but also delays the other diseases of aging with little or no side effects, then the door would be open to prescribing everyone take 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!




There are those who believe, completely and unquestioningly, that progress in medicine cannot occur without omnipresent regulation to suppress fraud. They point to the fraud that occurs anyway under heavily regulated development as the reason why. They believe that the vast overkill, perverse incentives, and needless hoop-jumping of FDA trials are needed to vet every last new therapy. But there will always be fraud, what works and what doesn't work will be established even without formal trials, and the most rapid progress in commercializing modern medicine, such as stem cell therapies, occurs in the least regulated of the wealthy regions of the world. This Economist article is an excellent example of the way in which people learn the wrong lesson from the state of the world, and accept without question what they are told by those politicians, bureaucrats, and businesspeople who have a vested short-term interest in the continuation of the US-styled system of medical regulation, no matter how harmful it is to progress.

Here is a JAMA article on the epidemiological consequences of increased obesity, written from a conservative point of view - i.e. the author believes that advancing medical technology will not greatly increase life span in the foreseeable future. "In 1900, [infectious disease] was a major concern, and the most common causes of death in the United States and in many parts of the world at the time were pneumonia and tuberculosis. Today, most individuals die of cardiovascular disease or cancer. This dramatic shift in the illnesses that cause the majority of death and disability has been divided into 4 stages known as the epidemiologic transition. In the last 2 decades, however, a fifth stage, marked by an alarming increase in overweight and obesity and continued decreases in physical activity, has emerged. ... By the mid 1960s, the United States had entered the fourth stage of delayed degenerative diseases. Cardiovascular disease mortality declined, related to preventive strategies such as smoking cessation programs and effective blood pressure control, acute coronary care units, and technological advances that included coronary artery bypass surgery. Despite the many advances in preventive medicine and treatment that reduced cardiovascular disease, the new stage of the epidemiologic transition, the age of obesity and inactivity, emerged to threaten the progress made in postponing illness and death to later in adult life spans. The steady gains made in both quality of life and longevity by addressing risk factors such as smoking, hypertension, and dyslipidemia are threatened by the obesity epidemic."

Researchers have shown that exercise boosts telomerase and slows the erosion of telomeres with age. Here is another small study that shows the telomere length association: "Telomere length (TL), a measure of replicative senescence, decreases with aging, but the factors involved are incompletely understood. To determine if age-associated reductions in TL are related to habitual endurance exercise and maximal aerobic exercise capacity (maximal oxygen consumption, VO(2)max), we studied groups of young (18 - 32 years) and older (55 - 72 years) sedentary and young and older endurance exercise-trained healthy adults. Leukocyte TL (LTL) was shorter in the older vs. young sedentary adults. LTL of the older endurance-trained adults was approximately [900 base pairs] greater than their sedentary peers and was not significantly different from young exercise-trained adults. LTL was positively related to VO(2)max due to a significant association in older adults. Stepwise multiple regression analysis revealed that VO(2)max independently explained approximately 60% of the variance in LTL. Our results indicate that LTL is preserved in healthy older adults who perform vigorous aerobic exercise and is positively related to maximal aerobic exercise capacity. This may represent a novel molecular mechanism underlying the 'anti-aging' effects of maintaining high aerobic fitness." Equally, it is still plausible that telomere length is only a marker for other processes. Either way, exercise is demonstrably good for your long term health - far better than any supplement or medical technology presently available.

Via PhysOrg.com, a look at yet another of the many approaches to a targeted cancer therapy: "In their study, the investigators developed a system containing two different nanomaterials that can be injected into the bloodstream. One nanomaterial was designed to find and adhere to tumors in mice and then sensitize tumor cells for the second nanoparticle, which kills the tumors. These scientists and others had previously designed nanometer-sized devices to attach to diseased cells or deliver drugs specifically to the diseased cells while ignoring healthy cells, but the functions of those devices, the researchers discovered, often conflicted with one another. ... For example, a nanoparticle that is engineered to circulate through a cancer patient's body for a long period of time is more likely to encounter a tumor, However, that nanoparticle may not be able to stick to tumor cells once it finds them. Likewise, a particle that is engineered to adhere tightly to tumors may not be able to circulate in the body long enough to encounter one in the first place. ... the scientists demonstrated in their experiments that a tumor growing in a mouse can be arrested and then shrunk."

Via In the Pipeline, I see that research groups are suggesting that some of the data for resveratrol (and other possible calorie restriction mimetics developed by Sirtris) is invalid, and previously reported beneficial effects on mice cannot be replicated: "Last fall, a group at Amgen published a study suggesting that some of the SIRT1/resveratrol connections might be due an an experimental artifact caused by a particular fluorescent peptide. Now a group at Pfizer has piled on in the Journal of Biological Chemistry. They're looking over resveratrol and a series of sirtuin activators described by the Sirtris group in Nature. And unfortunately, they also find trouble due to fluorogenic peptides. The TAMRA fluorophore on their peptide substrates seems to pervert the assay. While the Sirtris compounds looked like activators initially, switching to the native peptide substrates showed them to be worthless. Further study (calorimetry) showed that the activator compounds bind to a complex of SIRT1 and the fluorescent peptide substrate, but not to SIRT1 itself (or in the presence of native substrate without the fluorogenic group). That's not good." The researchers also failed to replicate beneficial health effects in their studies on mice. "Basically, these folks have thrown down the gauntlet: they claim that the reported Sirtris compounds do not do what they are claimed to do, neither in vitro nor in vivo, and are worthless as model compounds for anything in this area of study."

We should expect gene variants associated with human longevity to also be associated with lowered risk of age-related disease. Here is one example: "In a 2003 study, Dr. Lipton and his colleagues identified the cholesteryl ester transfer protein (CETP) gene variant as a 'longevity gene' in a population of Ashkenazi Jews. The favorable CETP gene variant increases blood levels of high-density lipoprotein (HDL) - the so-called good cholesterol - and also results in larger-than-average HDL and low-density lipoprotein (LDL) particles. The researchers of the current study hypothesized that the CETP longevity gene might also be associated with less cognitive decline as people grow older. To find out, they examined data from 523 participants from the Einstein Aging Study, an ongoing federally funded project that has followed a racially and ethnically diverse population of elderly Bronx residents for 25 years. At the beginning of the study, the 523 participants - all of them 70 or over - were cognitively healthy, and their blood samples were analyzed to determine which CETP gene variant they carried. They were then followed for an average of four years and tested annually to assess their rates of cognitive decline, the incidence of Alzheimer's disease and other changes. ... We found that people with two copies of the longevity variant of CETP had slower memory decline and [a] 70 percent reduction in their risk for developing Alzheimer's disease."

Yet another study to show that exercise likely does more to slow age-related mental degeneration than any presently available medical technology: "Moderate physical activity performed in midlife or later appears to be associated with a reduced risk of mild cognitive impairment, whereas a six-month high-intensity aerobic exercise program may improve cognitive function in individuals who already have the condition ... A total of 29 participants completed the study. Overall, the patients in the high-intensity aerobic exercise group experienced improved cognitive function compared with those in the control group. These effects were more pronounced in women than in men, despite similar increases in fitness. The sex differences may be related to the metabolic effects of exercise, as changes to the body's use and production of insulin, glucose and the stress hormone cortisol differed in men and women. ... In another report [a] total of 198 participants (median or midpoint age, 83 years) were determined to have mild cognitive impairment and 1,126 (median age 80) had normal cognition. Those who reported performing moderate exercise - such as brisk walking, aerobics, yoga, strength training or swimming - during midlife or late life were less likely to have mild cognitive impairment. Midlife moderate exercise was associated with 39 percent reduction in the odds of developing the condition, and moderate exercise in late life was associated with a 32 percent reduction. The findings were consistent among men and women."

Via EurekAlert!: researchers have "revealed a previously unknown mechanism that may drive the early brain function deterioration of Alzheimer's victims, thus opening a new exploratory path in the quest for an Alzheimer's cure. ... Researchers have known for years that a substance called amyloid-beta gums up brain cells when it becomes too concentrated, because it forms damaging deposits on the cells known as plaques. These prevent normal electrical signal generation in the cells, eventually killing them. That drives the memory loss and other problems that plague Alzheimer's sufferers. Most Alzheimer's studies have focused on brain cells already damaged by amyloid-beta or the effects of high concentration of amyloid-beta. [This study] instead explored impacts of very low amyloid-beta concentrations on healthy cells in an effort to mimic the earlier stages of Alzheimer's. ... though there are no outward signs of damage, exposure to moderate amyloid-beta concentrations somehow prevents electrical signals from traveling normally through the cells. Because the effect is seen in otherwise healthy cells, [researchers believe] the team may have uncovered a critical process in the progression of Alzheimer's that could occur before a person shows any known signs of brain impairment."

From Nanowerk: "Proteins are the most important molecules inside our body. There are thousands of [types of] proteins in a single cell alone and they control our physiological reactions, metabolism, cellular information flow, defense mechanisms - pretty much everything. No wonder then that most human diseases are related to the malfunctioning of particular proteins. In contrast to gene therapy - where a gene is placed inside a cell to either replace a defective gene or to increase the amount of a specific gene in order to produce a higher amount of a desired protein - protein therapy works by directly delivering well-defined and precisely structured proteins into the cell to replace the dysfunctional protein. This approach avoids the difficulties and potential problems of gene therapy and is generally considered the most direct and safe approach for treating disease. The problem with protein therapy, which limits its practical use in medicine, is the mode of delivery. Administration of proteins via oral, intravenous, intra-arterial, or intramuscular routes show low delivery efficiency and often the therapeutic protein is metabolized or cleared before it can enter the target tissue. A team of scientists at UCLA has now demonstrated a general, effective, low-toxicity intracellular protein delivery system based on single-protein nanocapsules. This work opens a new direction not only for protein therapy but also for cellular imaging, tumor tracking, cosmetics and many other applications."

Here is an open access review of what is presently known of the ways in which cellular senescence contributes to aging: "Cellular senescence is a mechanism that induces an irreversible growth arrest in all somatic cells. Senescent cells are metabolically active but lack the capacity to replicate. ... While induction of senescence is considered a major natural barrier against the uncontrolled proliferation characteristic of cancer, accumulation of senescent cells contributes to the process of aging and might promote tumor development. Senescent cells that appear to be resistant to apoptosis might be involved in the general organ dysfunction associated to aging and eventually promote cancer. It is widely accepted that the decline of organs and tissue function observed to occur with aging is associated with the accumulation of senescent cells. ... increased genomic instability is associated to inefficiency in DNA double strand repair ability of presenescent and senescent cells accumulating with aging. In addition, senescent cells might favor a [pro-cancer] tissue environment by secreting growth factors, extracellular matrix components and inflammatory cytokines that disrupt tissue integrity. Therefore, it has been suggested that senescence contributes to the process of aging and protects cells from uncontrolled growth makes it a cellular process beneficial or detrimental depending on the age of the organism. This suggests that senescence is an antagonistically pleiotropic phenomenon. For this reason senescence has been ironically defined as the Dr Jekyll and Mr. Hyde of aging." Therefore we should use targeted cell killing therapies to remove senescent cells.



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