From Depressed Metabolism: “The debilitating effects of a stroke are the result of the (delayed) neuronal death that follows an ischemic insult to the brain. In cryonics, biochemical or freezing damage to cells does not necessarily produce irreversible cell death because damaged cells are stabilized by cold temperatures. As such, morphological preservation of brain cells can co-exist with loss of viability. Therefore, securing viability of brain cells is a sufficient but not a necessary condition for resuscitation of cryonics patients. Future cell repair technologies are assumed to infer the original viable state of the cells from their morphological properties. This does not mean that conventional stroke research does not have any relevance for evaluating the technical feasibility of cryonics. Extensive delays between the pronouncement of legal death and the start of cryonics procedures could alter the structural properties of cells to such a degree that meaningful resuscitation is even problematic with advanced nanomedical cell repair technologies. This is one of the reasons why Alcor complements the cryopreservation process with stabilization procedures to secure viability of the brain after pronouncement of legal death.”
An interesting study that provides another view of the relationship between accumulating damage, repair systems, and life span in cells: “Yeast cells, much like our own cells, have a finite ability to reproduce themselves. A ‘mother’ cell can only produce 20-30 ‘daughters’ before it loses the ability to replicate and dies. … Multidrug resistance (MDR) proteins are best known for helping cancer cells expel anticancer drugs - hence their name - but they also ferry compounds in and out of normal cells. [Researchers] found that yeast lacking certain MDR proteins have a shorter reproductive lifespan; they produce fewer daughter cells. Yeast engineered to contain more of these pumps, however, can produce more daughters. … during division, the mother conserves damaged proteins and other cellular components that could prove harmful to the bud. … Indeed, some research groups have posited that the mother’s finite reproductive capability is the result of accumulating these damaged and toxic compounds. … yeast division also results in an unequal distribution of MDR proteins. The mother cell retains the original MDR proteins while the bud gets young, newly formed MDR proteins. Because the mother’s supply is never replenished, she has to rely on the pool of MDR proteins that she’s born with. … Over time these proteins decay. Some lose only part of their function; others may stop working altogether.”
In a nutshell, this is why research into so-called accelerated aging conditions may be relevant to longevity science: “One of the many debated topics in ageing research is whether progeroid syndromes are really accelerated forms of human ageing. The answer requires a better understanding of the normal ageing process and the molecular pathology underlying these rare diseases. Exciting recent findings regarding a severe human progeria, Hutchinson-Gilford progeria syndrome, have implicated molecular changes that are also linked to normal ageing, such as genome instability, telomere attrition, premature senescence and defective stem cell homeostasis in disease development. These observations, coupled with genetic studies of longevity, lead to a hypothesis whereby progeria syndromes accelerate a subset of the pathological changes that together drive the normal ageing process.” This same viewpoint - that each of the accelerated aging conditions represents a different facet of normal aging run wild - holds up for well other conditions, such as Werner syndrome, given the evidence amassed to date.
The latest Methuselah Foundation newsletter is out: “2010: Where We Are Now: Methuselah Foundation took on a big challenge: extending healthy human life. From SENS to My Bridge 4 Life, we’ve supported and incentivized major initiatives and research to fulfill our mission. In 2010 we are focusing our attention on tissue and whole organ engineering. Read this newsletter and follow the links to our site to learn more about what we are doing now so you live longer and healthier. … This year we are focusing our efforts on tissue engineering and organ replacement. We are looking ahead 10 years and projecting that, with our help, everyone who needs an organ will get an organ. … Prizes have proven to be the most powerful tool for inspiring radical scientific breakthroughs. That’s why we offer prizes, including the recently announced NewOrgan Prize. The end result will allow many people to live longer and - if history is an indicator - the many innovations that come as a result of this work are unimaginable today. To build a replacement organ, from a patients own cells, and have it fully function, scientists must first develop and preserve all the tissues that build that organ - including muscle, nerves, arteries and veins. … Leaders in the science of organ engineering have joined the NewOrgan Advisory Board. … The members of our Scientific Advisory Board are frontrunners in the research and development of new organ technology. ”
From ShrinkWrapped: “If a physical change affects half of all people as they age, this would seem to suggest that it is a normal variant of human aging, which to the best of our knowledge is an accumulation of metabolic and genetic errors that accrue as we get older until some sub-unit(s) of the processes reach a threshold at which continued functioning of the body is impossible. Our current regulatory apparatus remains trapped in a 20th century mindset which fails to recognize how various diseases are nothing more than unfortunate variants of the aging process that all of us will one day fall prey to. For example, in Alzheimer’s ‘Disease’ errors of metabolism (malformed proteins) in neurons in the brain lead to an accumulation of defective protein parts which eventually disrupt the functioning of the neuron, ultimately killing it. When this process has gone on long enough to have damaged and destroyed some as yet unknown fraction of the brain, the person becomes neurologically symptomatic. This ‘Disease’ is not communicable, nor is it caused by an exogenous agent. The damage to the brain occurs as the result of biological failure that all of us will have to face in one form or another. … The FDA does not recognize aging as a treatable condition and only approves treatment for ‘Disease.’ … Because the FDA only evaluates treatments for Diseases, and its definition of disease versus aging is completely arbitrary (why is Type II Diabetes a disease while Sarcopenia, the loss of muscle mass and function that accompanies aging, is not?) we are forced to develop treatments that primarily address symptoms rather than either repairing damage or rejuvenating systems.”
KurzweilAI looks at the recent scientific publication promoted by the LifeStar Institute: “Unfortunately, most biogerontologists see aging-intervention strategies as a considerable deviance from mainstream thinking, which is based on the notion that aging is a certainty and that pursuit of any kind of ‘fountain of youth’ or life-extension therapies will only end in failure. But de Grey is not swayed by the skeptics. He says perspectives are changing … Five of the other authors [of the paper] are among the absolute top tier of biogerontologists, whose views are universally respected in the field. Their voice here will make a huge impact on thinking about the issue, both within the field and beyond. The surprising conclusion from the past two decades of research on biological aging is that aging is plastic. Within a species, maximum life span is not fixed, but can be increased by dietary manipulation (particularly calorie restriction) or genetic manipulation. … But a new world of indefinite lifespans has also raised questions about potential population impacts. … ‘Contrary to what is widely assumed, however, the net effect should be relatively minor,’ the authors respond, reasoning that new human births have a greater effect on population than adding a fraction of life span to existing humans. … A policy of aging as usual will lead to enormous humanitarian, social, and financial costs. Efforts to avert that scenario are unequivocally merited, even if those efforts are costly and their success and full consequences uncertain. To realize any chance of success, the drive to tackle biological aging head-on must begin now.”
The bare leg season is now in full swing — unless varicose veins have you covering up all summer long.
A recent paper points to mitochondrially induced hormesis as a root cause of increased longevity with reduced calorie intake - which meshes well with the role of autophagy in this process. It confirms the importance of mitochondria in longevity, and once again shows that a little ongoing damage is actually a good thing: “Calorie restriction (CR) is the only proven regimen which confers lifespan extension benefits across the various phyla right from unicellular organisms like yeast to primates. In a bid to elucidate the mechanism of calorie-restriction-mediated life span extension, the role of mitochondria in the process was investigated. In this study, we found that the mitochondrial content in CR cells remains unaltered as compared to cells grown on nonrestricted media. However, mitochondria isolated from CR cells showed increased respiration and elevated reactive oxygen species levels without augmenting adenosine triphosphate (ATP) generation. The antioxidant defense system was amplified in CR mitochondria, and in CR cells a cross protection to hydrogen-peroxide-induced stress was also observed. Moreover, we also documented that a functional electron transport chain was vital for the life span extension benefits of calorie restriction. Altogether, our results indicate that calorie restriction elicits mitohormetic effect, which ultimately leads to longevity benefit.”
Better maintenance means a longer life, as illustrated by the importance of autophagy in calorie restriction (CR). Researchers are now branching out beyond CR to find other ways of influencing metabolism to better maintain cells: “The conserved insulin-signaling pathway has drawn a significant amount of attention over the past few years as a major lifespan determining signaling network. In many systems, impairing this pathway impedes the ability of caloric restriction (CR) to enhance lifespan, suggesting that nutrient sensing is key to CR. … the Titorenko laboratory [tested] the hypothesis that networks exist within cells that are not inducible, but act constitutively to extend the lifespan of cells regardless of nutrient availability … [the study] presents an original screen designed to isolate molecules that further lengthen the life span of yeast under calorie restriction rather than imitating this effect. … Among the chemical compounds identified, the authors focus on one group representing 6 bile acids compounds, the most efficient of them being lithocholic acid (LCA). Bile acids are mildly toxic oxidized derivatives of cholesterol that play important roles in lipid uptake by the intestine.”
A press release: “In a discovery that made headline news around the world, Dr. Zheng Cui, of the Wake Forest University School of Medicine, developed a colony of mice with super-charged granulocytes that successfully fight off many forms of virulent cancer. … In a surprising turn of events Dr. Cui also found that a similar cancer-killing activity is present in the granulocytes of some healthy humans. … When the Life Extension Foundation learned that this potential cancer cure was not being funded, it immediately made a $200,000 grant to fund the study at the South Florida Bone Marrow/Stem Cell Transplant Institute … This new clinical trial will test this approach in humans with advanced cancer, including metastases, who have not been helped by conventional cancer therapies. The trial has received an IND (investigational new drug) status from the Food and Drug Administration (FDA) and Institutional Review Board approval. … In January of this year, Dr. Maharaj notified the Life Extension Foundation that progress was being slowed because expected funding sources had dried up. Life Extension responded with another grant of $600,000 to further advance what could be a cure for cancer.”