So what is Sirtris up to these days? The startup was founded to investigate a line of calorie restriction mimetic compounds based on sirtuin biochemistry, and acquired for a very large sum by GlaxoSmithKline. The hope was that something to modestly slow aging would emerge - though even if so, development would be sidelined into making a therapy for diabetes or something similar, as the FDA outright forbids the commercial development of therapies to treat aging. A sad state of affairs in the land once known and the land of the free, to be sure, but it is what is.

Unfortunately for Sirtris, though not for their early investors, little of practical use has so far emerged from their work. It looks very much like the best case end result will indeed be something like a drug candidate to alleviate some of the consequences of obesity, diabetes or metabolic syndrome, all conditions that the vast majority of sufferers could have avoided through leading a healthier lifestyle, and could still reverse by leading a healthier lifestyle. Given the state of the world today, a medicine like that may yet make a great deal of money for GlaxoSmithKline, but it's not going to do anything of significance for human life spans. So, on the whole, the money poured into Sirtris looks like a failure wearing the clothes of success - and the more so because a bunch of people are going to see that researchers and investors made out like bandits from the deal and follow the same path, rather than trying to do something more ambitious and more useful.

Sirtris has been in the news again of late, with the completion of the latest study on the drug candidate SRT1720. This one doesn't appear to do what was originally thought - manipulate sirtuins in beneficial ways - but it does appear to be protective in obese mice. I see more optimism in the press coverage than is merited by the results, I think; a cynic might write that off to the size of the budget and the sophistication of the public relations crew at GlaxoSmithKline.

Longer Lives for Obese Mice, With Hope for Humans of All Sizes

Sustaining the flickering hope that human aging might somehow be decelerated, researchers have found they can substantially extend the average life span of obese mice with a specially designed drug. The drug, SRT-1720, protects the mice from the usual diseases of obesity by reducing the amount of fat in the liver and increasing sensitivity to insulin.

A Drug to Live Longer? Yes! (But Only If You're a Fat Mouse)

In the new study, SRT-1720 appeared to give obese mice the physiology of much leaner animals, which spared them from some of the negative health effects of excess weight. But the scientists note that while these mice lived longer than untreated obese mice, they didn't live nearly as long as untreated, normal-weight animals. Further, when the researchers looked at the maximum life span of the SRT-1720-treated fat mice, it wasn't much different from that of untreated obese mice. That means that the drug may just help animals enjoy more of whatever life they have, rather than actually extending it by any significant amount.

Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm

This is a UK press article on Halcyon Molecular, one of the new companies that has emerged from the pro-engineered-longevity community in recent years. You might also look back in the Fight Aging! archives for more on the views of the founders: "Even by Silicon Valley standards, the grand design drawn up by William and Michael Andregg is hugely ambitious. Halcyon Molecular, the company that the brothers founded in 2008, is developing a way to sequence the human genome - and thus unlock the deepest secrets of DNA - faster and cheaper than ever before. ... William is 29, Michael just a year older, and both are college drop-outs - but given Silicon Valley's impressive track record for nurturing and funding obsessive, unconventional young innovators, their age is hardly unusual. The surprise is the long-term mission of Halcyon Molecular: to solve "the biggest challenge humans can individually face - disease and mortality", as the mission-statement poster in their office reception says. Put another way, they're supercharging the effort to map life's biological code in almost unimaginable digital detail and, by doing so, ultimately, to attempt to conquer death itself." The difference between the here and now and 20 years ago is that you declare your plans to defeat aging and age-related death and both be taken seriously and raise large sums of money for research and development, both inside and outside the scientific community. There has been a sea change in attitudes towards engineered longevity as a goal, and that is one of the reasons that significant progress will be made in the years ahead: things happen when people start earnestly working to make them happen.

Link: http://www.independent.co.uk/life-style/gadgets-and-tech/news/2335404.html

Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm

An old Fight Aging! post is dusted off, rewritten, and published at h+ Magazine: "I'm not going to try to convince you that the foreseeable future is a wondrous place: either you accept the implications of the present rate of technological progress towards everything allowed by the laws of physics, in which case you've probably thought this all through at some point, or you don't. Life, space travel, artificial intelligence, the building blocks of matter: we'll have made large inroads into bending these all to our will within another half century. Many of us will live to see it even without the benefits of medical technologies yet to come: growing up without the internet in a 1960s or 1970s urban area will be the new 1900s farmboy youth come 2040. Just like the oldest old today, we will be immigrants from a strange and primitive near-past erased by progress, time travelers in our own lifetimes. A century is an exceptional life for a human, but far greater spans of years will be made possible by the technologies of the 21st century. I'll plant a flag way out there on the field and claim a million years ... Despite being out there, the million year life span is not an unsupported pipe dream. Living for a million years is a goal that can be envisaged in some detail today: the steps from here to there laid out, the necessary research and development plans outlined, and the whole considered within the framework of what is permissible under the laws of physics, and what the research community believes can be achieved within the next 20, 50, or 100 years."

Link: http://hplusmagazine.com/2011/08/19/the-million-year-life-span/

Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm

Looking at the near time, it seems that the next five years will see the tissue engineering community move from a few trials and some impressive demonstrations to real, commercialized work available in a scattering of clinics. Few of those clinics will be in the US, of course, as the FDA will add a cost of years and vast sums through the entirely unnecessary process of going from "can do" to "can do and allowed to do" - but the capabilities will exist. Take this, for example:

Stem cell researchers in Hong Kong and the United States are trying to grow spare parts for the human heart that may be ready for tests on people within five years ... When you get a heart attack, there is a small time window for a cure when the damage is still small. You can cure with a patch, a small tissue, so you won't progress to late stage heart failure ... The team will use approved human embryonic stem cell lines to build these human heart muscle strips, as well as [biological pacemaker tissues] for people with arrhythmia, or irregular heart beat.

The team plans first to transplant these muscle strips and pacemakers into pigs, and, if successful, to move to human clinical trials where they will transplant parts of the heart that are grown using the patients' own stem cells in about five years.

You might compare the research effort discussed in the article quoted above to other recent work on patching a damaged heart using stem cells. The two are illustrative of quite different directions in regenerative medicine: one path is to put cells into the body and let them build new tissue and repair damage in situ, whilst the other is to build new tissue structures (or even entire organs) outside the body and then surgically implant them. Personally, I favor the former approach, provided it can be made to achieve the same degree of effectiveness in the future - despite advancing technology, surgery remains surgery, and not something that any sane person would want to undergo unless absolutely necessary.

Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm

An open access paper on the biology of one of the longest-lived engineered mouse species: "The age-associated decline in tissue function has been attributed to ROS-mediated oxidative damage due to mitochondrial dysfunction. The long-lived Ames dwarf mouse exhibits resistance to oxidative stress, a physiological characteristic of longevity. It is not known, however, whether there are differences in the electron transport chain (ETC) functions in Ames tissues that are associated with their longevity. In these studies we analyzed enzyme activities of ETC complexes, CI-CV and the coupled CI-CII and CII-CIII activities of mitochondria from several tissues of young, middle aged and old Ames dwarf mice and their corresponding wild type controls to identify potential mitochondrial prolongevity functions. Our studies indicate that post-mitotic heart and skeletal muscle from Ames and wild-type mice show similar changes in ETC complex activities with aging, with the exception of complex IV. Furthermore, the kidney, a slowly proliferating tissue, shows dramatic differences in ETC functions unique to the Ames mice. Our data show that there are tissue specific mitochondrial functions that are characteristic of certain tissues of the long-lived Ames mouse. We propose that this may be a factor in the determination of extended lifespan of dwarf mice."

Link: http://impactaging.com/papers/v3/n8/full/100357.html

Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm

The SENS Foundation Academic Initiative is a long-term project aimed at helping to build the research community of tomorrow - one interested in the repair and reversal of aging, rather than a next generation that is only interested in slowing down aging a little via manipulation of metabolism, a simple repeat of today's research community. Here is an update from the Foundation: "The SENS Foundation Academic Initiative's new structure is actively in the process of being implemented, and involves a number of significant changes. Among these are the separation of the Initiative into branches, an updated membership system that allows students to become involved more easily and in more ways, the creation of volunteer committees, and the addition of outreach projects to the Initiative's activities. ... There will be three branches: Research, Outreach, and Education. The Research branch will be focused on the actual accomplishment of scientific research. This research will always be done with an eye to publication, but its most important function will be to provide our students with learning experiences, to help them develop into career scientists. The Outreach branch will be focused on spreading the word about the Academic Initiative and about the SENS Foundation, while the Education branch will be focused on educating students about science and SENS. ... While the Academic Initiative has long helped students to complete research projects, it has not done much in the past to encourage students to be advocates of the Initiative and the SENS Foundation. This will change with the implementation of outreach projects. These will generally be simple, off-the-shelf projects that students can finish in an afternoon, such as printing fliers from a pre-made template and distributing them at their university."

Link: http://sens.org/node/2345

Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm

What happens across your lifetime to change you from young to old is known as stochastic damage - the integrity of your bodily systems nibbled away, one damaged or misplaced clump of atoms at a time. At the detail level of molecular machinery, this is basically random. But the process is statistically predictable when you start to look at the bigger picture: our bodies are all, sadly, headed downhill in much the same general direction, and we can even talk about trends, environmental factors, and speeds of decline when we examine large groups of people.

For you, personally, what this means is that you have a ticket to ride and you can steer the bounds of the possible by your actions. But there's no such thing as absolute control - there are only risks to be shifted one way or another. Laze around and grow fat, and watch the risk of diabetes, cancer, and dementia grow much larger. Or smoke and suffer the likely consequences. Or avoid doctors like the plague for two dozen years and you're making your own bad luck, slowly but surely.

Some people sail through all that exactly because they were lucky, or both lucky and possessed of rare protective genes. Equally, you could do everything right, live the healthiest life possible, and get nailed by cancer in your twenties, or by the sudden onset of an unsuspected genetic condition in your thirties, or by an autoimmune disease despite no history of it in your family. Or, hell, by some idiot operating heavy machinery without a license while you're minding your own business on the sidewalk. These things happen. They're rare, but the point is that they're on the ticket: all you can do is swing the odds.

Some people die young and despite living well: it happens. I'm sure we can all think of a few we've known. But that doesn't remove any of the value of living well, doing the right things for your health, and generally trying to keep on the right side of heavy machinery. It's a matter of odds. Too many people look at disease in later life as exclusively bad luck, whereas they in fact had a hand in moving the needle the wrong way:

Lifetime physical inactivity interacts with secondary aging (i.e., aging caused by diseases and environmental factors) in three patterns of response. First, lifetime physical inactivity confers no apparent effects on a given set of physiological functions. Second, lifetime physical inactivity accelerates secondary aging (e.g., speeding the reduction in bone mineral density, maximal oxygen consumption, and skeletal muscle strength and power), but does not alter the primary aging of these systems. Third, a lifetime of physical activity to the age of ~60-70 years old totally prevents decrements in some age-associated risk factors for major chronic diseases, such as endothelial dysfunction and insulin resistance. The present review provides ample and compelling evidence that physical inactivity has a large impact in shortening average life expectancy. In summary, physical inactivity plays a major role in the secondary aging of many essential physiological functions, and this aging can be prevented through a lifetime of physical activity.

In some things we can make our own luck; in others we can't. Not much that can be done today about the bolt from the blue cancer in your teens, or the genetics that dealt you a heart that'll have to be nursed like the engine in a second hand car for the rest of your life. But for the rest of it: the prepared and the foresighted have what looks like great luck in life - at least from the perspective of people who didn't pay attention to all the groundwork that led to that point.

Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm

That part of the research community focused on manipulating metabolism to slow down aging has advanced to the point of considering multiple distinct simultaneous changes to achieve the desired end result: "Modern medicine is directed towards the prevention, detection and cure of individual diseases. Yet, current medical models inadequately describe aging-associated diseases. We now know that failure in longevity pathways including oxidative stress, multisystem dysregulation, inflammation, sarcopenia, protein deposition and atherosclerosis are associated with age-related diseases. Such longevity pathways are potential targets for therapeutic intervention. Interventions in specific pathways have been shown to ameliorate and postpone the aging phenotype by activation of multiple genes. The strategy that we propose in this paper is to apply interventions simultaneously on complementary longevity pathways to achieve a synergistic result. For instance, aging is known to attenuate the HSF1 pathway leading to production of very toxic beta-amyloid fibrils. Consequently, the FoxO pathway is activated, resulting in the formation of less toxic high molecular weight aggregates as a defense mechanism. Thus the simultaneous upregulation of the HSF1 and FoxO pathways could potentially decrease protein deposition and proteotoxicity, thereby retarding or possibly preventing the onset of neurodegenerative diseases. Modulating these two pathways may also delay the onset of other age-related pathologies including cognitive decline, cancer, diabetes and cardiovascular disease due to its multi-gene effect. "

Link: http://www.ncbi.nlm.nih.gov/pubmed/21834787

Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm

Researchers find what looks to be a proxy measure for the degree to which a person is sedentary - but of course there might be other important correlations here, such as with wealth or intelligence: "Watching TV for an average of six hours a day could shorten the viewer's life expectancy by almost five years ...The impact rivals that of other well known behavioural risk factors, such as smoking and lack of exercise, the study suggests. Sedentary behaviour - as distinct from too little exercise - is associated with a higher risk of death, particularly from heart attack or stroke. Watching TV accounts for a substantial amount of sedentary activity, but its impact on life expectancy has not been assessed, say the authors. They used previously published data on the relationship between TV viewing time and death from analyses of the Australian Diabetes, Obesity and Lifestyle Study (AusDiab), as well as Australian national population and mortality figures for 2008, to construct a lifetime risk framework. AusDiab is a national survey of a representative sample of the population, starting in 1999-2000, and involving more than 11,000 adults aged 25 or older. The authors then constructed a risk framework for the Australian population in 2008, based on the answers the survey participants had given, when quizzed about the total amount of time they had spent in the previous week watching TV or videos. ... These figures compare with the impact of other well known lifestyle factors on the risk of death from cardiovascular disease after the age of 50, including physical activity and obesity. For example, other research has shown that lifelong smoking is associated with the shortening of life expectancy by more than 4 years after the age of 50, with the average loss of life from one cigarette calculated to be 11 minutes - equivalent to half an hour of TV watching, according to the authors' risk framework." I applaud the researchers for finding a way to present their work that will likely get a lot of play in the media.

Link: http://www.eurekalert.org/pub_releases/2011-08/bmj-dtq081511.php

Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm

The aged immune system begins to fail at its job for a variety of reasons that seem to have more to do with its evolved structure and control systems than with the outright incapacity of immune cells, or the inability to generate more immune cells. The immune system evolved to work very effectively in younger life, and that comes at the cost of controlling processes that fall down badly in the long term.

A small reserve of memory cells is needed to respond effectively to previously encountered threats - one reserve per threat. The more threats you have encountered, the more cells become devoted to memory; eventually you don't have enough naive T cells left to mount any sort of effective defense.

Given the capabilities that remain in the body, an aged immune system could, in theory, get up to fight and fight well - but it doesn't. That shortcoming may be addressed by selectively manipulating the system and its cells, however. For example, in recent years researchers have demonstrated that we can (a) intervene via modern medicine to expand the population of useful immune cells, or (b) destroy the accumulation of useless immune cells and thereby immediately free up space so that the body creates more useful immune cells, or even (c) wipe out and recreate the entire immune system as a fresh start, which works to cure autoimmune diseases in which immune cells run amok and attack the body.

I noticed a research release today that discusses the identification of another potential source of useful cells in the aged immune system, cells normally left inactive thanks to the evolved control systems that focus on early life at the expense of later life. The researchers show that these cells can be activated for duty:

Professor Arne Akbar of UCL (University College London), who led this research, explains "Our immune systems get progressively weaker as we age because each time we recover from an infection a proportion of our white blood cells become deactivated. This is an important process that has probably evolved to prevent certain cancers, but as the proportion of inactive cells builds up over time our defences become weakened. What this research shows is that some of these cells are being actively switched off in our bodies by a mechanism which hadn't been identified before as important in ageing in the immune system. Whilst we wouldn't want to reactivate these cells permanently, we have an idea now of how to wake them from their slumber temporarily, just to give the immune system a little boost."

...

When the researchers blocked this newly identified pathway in the lab they found that the white blood cells appeared to be reactivated. Medicines which block this pathway are already being developed and tested for use in other treatments so the next step in this research is to explore further whether white blood cells could be reactivated in older people, and what benefits this could bring.

I see it as a good sign that there are a range of different potential lines of research that might lead to varying degrees of immune system rejuvenation, temporary or otherwise. Variety and competition are signs of a healthy field of medicine.

Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm