Fight Aging! Newsletter, July 4th 2011

FIGHT AGING! NEWSLETTER
July 4th 2011

The Fight Aging! Newsletter is a weekly email containing news, opinions, and happenings for people interested in aging science and engineered longevity: making use of diet, lifestyle choices, technology, and proven medical advances to live healthy, longer lives. This newsletter is published under the Creative Commons Attribution 3.0 license. In short, this means that you are encouraged to republish and rewrite it in any way you see fit, the only requirements being that you provide attribution and a link to Fight Aging!

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CONTENT

- Two Months Until SENS5
- There is No "I Don't Know What to Do With My Life"
- Progress on Engineered Blood Vessels
- Considering Why Type 2 Diabetes is Age-Related
- Discussion
- Latest Headlines from Fight Aging!

TWO MONTHS UNTIL SENS5

Time flies, and the fifth Strategies for Engineered Negligible Senescence conference (SENS5) is only two months away:

https://www.fightaging.org/archives/2011/07/two-months-left-until-the-sens5-conference.php

"The purpose of the SENS conference series, like all the SENS initiatives (such as the journal Rejuvenation Research), is to expedite the development of truly effective therapies to postpone and treat human aging by tackling it as an engineering problem: not seeking elusive and probably illusory magic bullets, but instead enumerating the accumulating molecular and cellular changes that eventually kill us and identifying ways to repair - to reverse - those changes, rather than merely to slow down their further accumulation. This broadly defined regenerative medicine - which includes the repair of living cells and extracellular material in situ - applied to damage of aging, is what we refer to as rejuvenation biotechnologies."

THERE IS NO "I DON'T KNOW WHAT TO DO WITH MY LIFE"

Some thoughts on priorities:

https://www.fightaging.org/archives/2011/06/there-is-no-i-dont-know-what-to-do-with-my-life.php

"There should be no such thing as 'I don't know what to do with my life.' Scratch that statement away and erase it, as it should be 'I will aid the development of life extension technology until I do know.' ... Our lives have a timer, and we are all well aware of it, for all that many of us prefer not to think about it at all. The whole structure of life and society revolves around the existence of that timer, as it ticks away the freedom we have remaining in which to find and work on something worthwhile. The rush to find meaning in life? There because we don't have enough time. The need to save for retirement and medical costs? The timer again, ticking away our health and ability to fend for ourselves. When you cannot see even the first shape of what will be your life's work, and time is ticking away, the best thing you can do is to offer a helping hand to those who work on making more time - scientists, advocates, and others who support research and development of rejuvenation biotechnologies. You can do that at the same time as you search for the cause or idea that truly speaks to you, and it beats slumping back into the grey doldrums that seem to afflict so much of our society: people who never found that fire inside, and who have no time left in which to do so."

PROGRESS ON ENGINEERED BLOOD VESSELS

Work on tissue engineered replacements for large blood vessels is proceeding apace:

https://www.fightaging.org/archives/2011/06/more-progress-on-engineered-blood-vessels.php

"Blood vessels grown in a laboratory were safely implanted in three kidney disease patients, enabling them to have regular dialysis without relying on traditional shunts that caused complications and failed, researchers said. The foot-long vessels were engineered from donor skin cells, grown on sheets and rolled around temporary supports to form a cylindrical shape. ... The engineered vessels had about a two-month storage life before they were implanted in the patients ... They have held up in mechanical and animal tests when used more than a year after they were made ... The grafts don't appear to trigger a response from the patients' immune systems, eliminating the need for powerful immune suppressing drugs and tests to match the cells used in the graft to the patients' tissue type."

CONSIDERING WHY TYPE 2 DIABETES IS AGE-RELATED

Type 2 diabetes is largely something you do to yourself through poor lifestyle choices maintained over the years. But poor lifestyle choices are not a monopoly held only by the old, so why is it that this condition occurs much more readily in older people?

https://www.fightaging.org/archives/2011/06/considering-why-type-2-diabetes-is-an-age-related-condition.php

"Becoming ever more obese and sedentary will hasten the onset of diabetes into ever earlier years of life, but older obese and sedentary people are still far more likely to suffer type 2 diabetes than are equally overweight and sedentary younger counterparts. So while failing to take care of your health at any age is just another form of self-harm, there are other, less avoidable processes taking place at the level of cells and organs that make older people more vulnerable. Here is an open access paper that reviews what researchers presently know of the decline of insulin-producing beta cells in the pancreas - which turns out to be not enough, as is still true of so much of our biochemistry. There are changes, cataloged and identified, but the chains of causation for those changes are poorly understood at best.

"I look on this as a good illustration of why the detailed, tissue by tissue, understand everything approach to repairing aging is doomed to take a very long time indeed. This is but one population of vital cells in one organ, one of the most studied forms of cell in past decades, and the research community remains far from a complete understanding as to how and why they fail with age. Better strategies to deal with aging exist - such as SENS - and need to gain wider support and adoption. SENS-like approaches work around the challenge posed by the sheer complexity of human biochemistry by focusing on the known common mechanisms of aging, the root causes from which there is good reason to believe all other changes descend. Repairing these root causes is the fast path to the first generation of rejuvenation biotechnology, and that, in my eyes, is the only real shot at building viable interventions in the aging process that will arrive in time to help us."

DISCUSSION

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!

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LATEST HEADLINES FROM FIGHT AGING!

A NOVEL VIEW OF STEM CELL DECLINE
Friday, July 1, 2011
https://www.fightaging.org/archives/2011/07/a-novel-view-of-stem-cell-decline.php
An open access paper: "One of the most important and complex diseases of modern society is metabolic syndrome. This syndrome has not been completely understood, and therefore an effective treatment is not available yet. We propose a possible stem cell mechanism involved in the development of metabolic syndrome. This way of thinking lets us consider also other significant pathologies that could have similar [or shared biological pathways], like lipodystrophic syndromes, progeria, and aging. All these clinical situations could be the consequence of a progressive and persistent stem cell exhaustion syndrome (SCES). The main outcome of this SCES would be an irreversible loss of the effective regenerative mesenchymal stem cells (MSCs) pools. In this way, the normal repairing capacities of the organism could become inefficient. ... Stem cell restoration has already demonstrated therapeutic activities in certain systems. For example, it is known that after a stroke, endogenous stem cells are mobilized from the bone marrow in an attempt to heal the damaged neural tissue. Most interestingly, a recent study demonstrated that stroke patients who exhibit a high level of stem cell mobilization have better functional outcomes as opposed to patients with a lower mobilization. ... If [MSCs exhaustion syndrome] is true, then a stem cell therapy approach could be feasible. For instance, ex vivo expansion and reinfusion of MSCs from the patient's own or from allogeneic donors, as evidence shows that MSCs are not immunogenic at all, have been already tested in many clinical trials .... In the best case scenario, MSCs therapy could retard the onset of irreversible lesions associated with metabolic syndrome or at least partially improve those already present."

ON LONGEVITY INSURANCE
Friday, July 1, 2011
https://www.fightaging.org/archives/2011/07/on-longevity-insurance-1.php
It is worth watching the prevalence of longevity insurance offerings, as this is a measure of the degree to which the actuarial community and insurance industry believes that increases in human life span will happen in the near future, but that they will not be large. For the insurer, longevity insurance is a bet on earlier than anticipated death: "Most people buy life insurance to protect against the risks of dying too soon. Now, there are new products offering the same protection if you live too long. It's known as longevity insurance, and there's clearly a huge market for it: Life expectancies are on the rise, cushy pensions are on the decline, and most people don't have enough savings to carry them through two decades or more of retirement. This is not lost on insurance companies, which would like you to think about the product as a pension of sorts - albeit one that you have to buy with your own money. ... But what happens if Merck invents the magic pill and we all live until 105? ... Continued improvements in medicine that allow people to live longer could create losses on our individual annuity business. but these would be more than offset by higher gains on the life insurance. ... Still [if] something like that were to happen, 'at some point, capacity might be limited.'" Companies that bet against large increases in longevity are likely to suffer greatly in decades to come - which is unfortunate for the rest of us, because these concerns are large enough to run to the nearest government for a bailout, and thus we all end up paying for collective bad bets.

STEPPING IN THE DIRECTION OF ARTIFICIAL CELLS
Thursday, June 30, 2011
https://www.fightaging.org/archives/2011/06/stepping-in-the-direction-of-artificial-cells.php
Artificial cells are one possible line of future biotechnology; devices built to resemble the body's building blocks, essentially nanomachines constructed of proteins. Here researchers take a modest step in that direction, by developing "a novel method of disguising nanoparticles as red blood cells, which will enable them to evade the body's immune system and deliver cancer-fighting drugs straight to a tumor. ... The method involves collecting the membrane from a red blood cell and wrapping it like a powerful camouflaging cloak around a biodegradable polymer nanoparticle stuffed with a cocktail of small molecule drugs. Nanoparticles are less than 100 nanometers in size, about the same size as a virus. ... This is the first work that combines the natural cell membrane with a synthetic nanoparticle for drug delivery applications. This nanoparticle platform will have little risk of immune response. ... Stealth nanoparticles are already used successfully in clinical cancer treatment to deliver chemotherapy drugs. They are coated in a synthetic material such as polyethylene glycol that creates a protection layer to suppress the immune system so that the nanoparticle has time to deliver its payload. ... today's stealth nanoparticle drug delivery vehicles can circulate in the body for hours compared to the minutes a nanoparticle might survive without this special coating. But in [this latest] study, nanoparticles coated in the membranes of red blood cells circulated in the bodies of lab mice for nearly two days. ... one of the next steps is to develop an approach for large-scale manufacturing of these biomimetic nanoparticles for clinical use. ... Researchers will also add a targeting molecule to the membrane that will enable the particle to seek and bind to cancer cells, and integrate the team's technology for loading drugs into the nanoparticle core so that multiple drugs can be delivered at the same time."

RAPAMYCIN VERSUS PROGERIA
Thursday, June 30, 2011
https://www.fightaging.org/archives/2011/06/rapamycin-versus-progeria.php
From the Technology Review: "The drug rapamycin has been found to reverse the effects of Hutchinson-Gilford progeria syndrome, a fatal genetic disease that resembles rapid aging, in cells taken from patients with the disease. Rapamycin, an immunosuppressant drug used to prevent rejection of transplanted organs, has already been shown to extend life span in healthy mice. Researchers hope the findings will provide new insight into treating progeria as well as other age-related diseases. Skin cells from patients with progeria show a slew of defects: deformities in their membranes, decreased growth, and early death. [Researchers] found that rapamycin could reverse these defects by enhancing the cells' ability to degrade the protein progerin, which accumulates in abnormal amounts in progeria patients. It's not yet clear whether the drug will have similar effects on animals or patients. But progeria researchers are planning a clinical trial of rapamycin. ... Researchers say the findings could be relevant beyond this rare genetic disease. Although accumulation of progerin is associated with progeria, the protein also accumulates in small amounts in normal cells, and may be partially responsible for the aging process."

MORE THAN YOU EVER WANTED TO KNOW ABOUT PRE-CRYOPRESERVATION TRANSPORT
Wednesday, June 29, 2011
https://www.fightaging.org/archives/2011/06/more-than-you-ever-wanted-to-know-about-pre-cryopreservation-transport.php
A long and fascinating post from Chronosphere details the extensive preparations that go into transporting the body of a cryonics patient for cryopreservation: "Many patients will be remote from the facility where cryoprotective perfusion will be carried out and will be transported by common carrier or private carrier over considerable geographical distances. In some cases it will be possible to move the patient using a specialized transport vehicle with on-going extracorporeal support. In other cases the distances will be sufficiently great that the only realistic option is iced-shipment in the absence of perfusion. It is often necessary to use a commercial air freight service to move the patient from one area of the United States to another (or from one country to another). ... Because of time constraints to get freight loaded rapidly, air freight is often not handled with care by airport personnel. ... Whenever possible, the Transport Technician should supervise the handling of the patient every step of the way, including on and off the aircraft. Due to recent terrorist acts it has become increasingly difficult for the Transport Technician to do this. Until quite recently it was usually easy for the Technician to get access to air freight facilities and the tarmac to supervise loading of the patient onto the aircraft. This is now all but impossible. However, it is still important to accompany the patient to the air freight depot and to emphasize that extra care should be used in handling the patient, and that every precaution should be taken against misrouting."

ELECTROPHILIC STRESS, MEMBRANES, AND AGING
Wednesday, June 29, 2011
https://www.fightaging.org/archives/2011/06/electrophilic-stress-membranes-and-aging.php
You may recall that composition of cell membranes is strongly correlated to species longevity - the idea being that some membranes are more resistant to the damage of reactive oxygen species than others, and that damage resistance at the cellular level ultimately translates into a longer-lived animal. Here is more on that topic: "This review begins with the premise that an organism's life span is determined by the balance between two countervailing forces: (i) the sum of destabilizing effects and (ii) the sum of protective longevity-assurance processes. Against this backdrop, the role of electrophiles is discussed, both as destabilizing factors and as signals that induce protective responses. Because most biological macromolecules contain nucleophilic centers, electrophiles are particularly reactive and toxic in a biological context. The majority of cellular electrophiles are generated from polyunsaturated fatty acids by a peroxidation chain reaction that is readily triggered by oxygen-centered radicals, but propagates without further input of reactive oxygen species(ROS). Thus, the formation of lipid-derived electrophiles such as 4-hydroxynon-2-enal (4-HNE) is proposed to be relatively insensitive to the level of initiating ROS, but to depend mainly on the availability of peroxidation-susceptible fatty acids. This is consistent with numerous observations that life span is inversely correlated with membrane peroxidizability and with the hypothesis that 4-HNE may constitute the mechanistic link between high susceptibility of membrane lipids to peroxidation and shortened life span. Experimental interventions that directly alter membrane composition (and thus their peroxidizability) or modulate 4-HNE levels have the expected effects on life span, establishing that the connection is not only correlative but causal. Specific molecular mechanisms are considered, by which 4-HNE could (i) destabilize biological systems via nontargeted reactions with cellular macromolecules and (ii) modulate signaling pathways that control longevity-assurance mechanisms."

LITHIUM AS TREATMENT FOR PARKINSON'S DISEASE
Tuesday, June 28, 2011
https://www.fightaging.org/archives/2011/06/lithium-as-treatment-for-parkinsons-disease.php
A number of interesting studies on lithium have turned up in recent years, such as its possible association with longevity in humans. Here researchers are testing it against Parkinson's disease: "A two-year study of the effects of lithium treatment on Parkinson's disease in mice has given researchers at the Buck Institute for Research on Aging hope that the drug may halt brain damage in humans with the degenerative disorder. The research found that lithium, the Food and Drug Administration-approved drug most commonly used to treat bipolar disorder, 'profoundly prevents the aggregation of toxic proteins and cell loss associated with Parkinson's disease' in mice. ... In the last couple of years, there's been kind of a growing body of data that suggests that lithium could have some neuroprotective effects ... Other diseases lithium treatment may benefit include Alzheimer's, Huntington's and Lou Gehrig's. ... In addition, recent studies have suggested that the naturally occurring substance may extend life span. ... The group is now doing preclinical research on dose level and other issues and hopes to raise funds for a clinical trial with humans as soon as possible. ... Nonetheless, it is too early to draw conclusions, [as] medications that appear to halt Parkinson's in animals don't necessarily work the same way in humans. Lithium's potential for toxicity is also of concern, particularly because Parkinson's patients are often quite fragile, he said. In at least two known cases, toxic levels of the drug have actually caused Parkinson's."

NEW LUNG-RELATED STEM CELL POPULATION DISCOVERED
Tuesday, June 28, 2011
https://www.fightaging.org/archives/2011/06/new-lung-related-stem-cell-population-discovered.php
Via EurekAlert!: researchers "have identified a new stem cell that participates in the repair of the large airways of the lungs, which play a vital role in protecting the body from infectious agents and toxins in the environment. The airways protect the body by producing and clearing mucus from the airways. The mucus is largely produced by specialized mucus glands in the airway and the mechanisms of normal and excessive mucus production are not well understood. However, this newly discovered lung stem cell for the mucus glands will likely yield new insights into this critical process. ... The study [represents] the first time anyone has found the cell of origin for the many types of cells that make up the mucus glands and that can also repair the surface epithelium. The finding, the study states, is of 'major importance to the field of lung regeneration.' ... For example, there currently are no treatments for excess mucus production, which we see in cystic fibrosis, asthma and chronic obstructive pulmonary disease (COPD). But if we can understand the mechanisms of how these stem cells repair the mucus glands, then we may be able to find a way to put the brakes on the system and prevent mucus over production."

LARGE MULTIVITAMIN STUDY SHOWS NO BENEFIT
Monday, June 27, 2011
https://www.fightaging.org/archives/2011/06/large-multivitamin-study-shows-no-benefit.php
This paper can be filed alongside those that show no benefit from the use of ingested antioxidants: "Although multivitamin/mineral supplements are commonly used in the United States, the efficacy of these supplements in preventing chronic disease or premature death is unclear. To assess the relation of multivitamin use with mortality and cancer, the authors prospectively examined these associations among 182,099 participants enrolled in the Multiethnic Cohort Study between 1993 and 1996 in Hawaii and California. During an average 11 years of follow-up, 28,851 deaths were identified. In Cox proportional hazards models controlling for tobacco use and other potential confounders, no associations were found between multivitamin use and mortality from all causes (for users vs. nonusers: hazard ratio = 1.07, 95% confidence interval: 0.96, 1.19 for men; hazard ratio = 0.96, 95% confidence interval: 0.85, 1.09 for women), cardiovascular diseases, or cancer. The findings did not vary across subgroups by ethnicity, age, body mass index, preexisting illness, single vitamin/mineral supplement use, hormone replacement therapy use, and smoking status. There also was no evidence indicating that multivitamin use was associated with risk of cancer, overall or at major sites, such as lung, colorectum, prostate, and breast. In conclusion, there was no clear decrease or increase in mortality from all causes, cardiovascular disease, or cancer and in morbidity from overall or major cancers among multivitamin supplement users."

IMMUNOTHERAPY TO CLEAR TAU AGGREGRATES IN ALZHEIMER'S DISEASE
Monday, June 27, 2011
https://www.fightaging.org/archives/2011/06/immunotherapy-to-clear-tau-aggregrates-in-alzheimers-disease.php
From the SENS Foundation: "Neurofibrillary tangles (NFT -- cytoplasmic inclusions composed of phosphorylated and abnormally-cleaved species of tau protein) accumulate in the aging brain, and at higher levels in Alzheimer's disease and in vulnerable regions in a range of other neurodegenerative diseases. ... [Researchers] have tested immunotherapies targeting tau aggregates in preclinical models of neurodegeneration caused by pathological tau species. .... Vaccination with human phosphorylated tau led to the clearance of tau pathology from the brains of immunized mice [and] In turn, these reductions in abnormal tau species were clearly linked to substantial improvements in cognitive deficits. This is an impressive advance. The authors have used vaccination with a human phosphorylated tau immunogen to effect the immunologic clearance of pathological tau aggregates associated with Alzheimer's disease, in a mouse model expressing wild-type human tau. They have intervened late, months after the initial development of cognitive deficits. ... the vaccine has not only elicited a robust immunological response, and cleared pathological tau species from brain regions of relevance to human disease, but have linked such clearance to improved cognitive function on several extensively-used tests. The new work is strong support for the therapeutic importance and tractability of the removal of pathological tau species from the brain - in Alzheimer's disease, in other tauopathies, and in the 'normal' degeneration of the aging brain. And it is yet another in a mounting series of reports offering support for the therapeutic heuristic of removing the damage of aging, to effect the rejuvenation of the body - and the mind."

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