The popular press will give just as much attention to an advance that extends life in healthy laboratory animals as they will to a technology demonstration that even partially reverses an artificially induced shortness of life. This is a problem, because the former is worthy of our attention, while it is almost always the case that the latter is not. Here is another example of the type from today's news:

Researchers at the University of Pittsburgh Medical Center genetically altered mice to make them age faster, making them old and weak in a span of 17 days. The scientists then injected the mice with stem cell-like cells taken from the muscle of young, healthy mice. The result was they reversed the aging process. The rapidly aging mice lived up to three times longer, dying after 66 days, rather than 28 days. The cell injection also appeared to make the animals healthier, improving their muscle strength and brain blood flow.

No, they did not reverse the aging process. What these researchers achieved was to partially (very partially) ameliorate the unnatural form of accelerated aging that they themselves created in these mice - which could be due to any number of mechanisms that have no application whatsoever to the treatment of normal aging.

You might recall that this same talking point came up a little over a year ago in connection with research into telomerase and accelerated aging:

It's interesting stuff, but unfortunately this present research is being headlined as "scientists reverse aging in mice" - which is absolutely not what was accomplished. Reversing an artificially created accelerating aging condition by removing its cause is not the same thing as intervening in normal aging, and it will rarely have any relevance to normal aging. ... The bottom line is that it is really only worth getting excited over a study that shows extension of life rather than an un-shortening of life. It's all too easy to create short-lived mice and then make them less short-lived - hundreds of studies have achieved this result in one way or another.

But this seems a little too subtle for much of the media - or, more cynically, perhaps it's more a matter that the employees of those press institutions don't really care all that much about accuracy or background for so long as the page views keep rolling in.

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

It has been an interesting year, and I suppose it is traditional at the tail end of December to cast a thoughtful eye back at the highlights. Which I will do, and the following items are in no particular order of importance or chronology.

This was the year that marked the end of the Longevity Meme, launched in 2001 and finally shut down and folded into Fight Aging!

2011 was also the year that I finally redesigned Fight Aging! - something I'd been threatening to get around to since somewhere in the middle of 2005. Speed of action is not high on the list of things to expect around these parts.

The SENS Foundation issued research reports that showed definite signs of progress - a million dollar budget in the prior year and concrete results starting to emerge from the research program focused on the means to repair the biological damage of aging.

Speaking of SENS, the Strategies for Engineered Negligible Senescence, the fifth SENS conference was held only a few months ago. There have been a range of presentations posted to the Foundation YouTube channel as high quality videos.

An important confirmation of the role of senescent cells in aging was accomplished in mice. Find a way to remove senescent cells and health and longevity benefit - that has been shown in action, and now the research community needs to develop a way to accomplish that goal that is better suited to clinical development of a therapy for humans.

This past year the Methuselah Foundation has refocused their efforts on establishing the New Organ Mprize as a part of the comprehensive strategy to accelerate tissue engineering and organ creation - and with it improve human longevity.

Max More has been working away as CEO of Alcor for the past year, making changes aimed at improving the transparency, community relations, and long term prospects for that part of the cryonics industry.

Some noteworthy progress was made early in 2011 in selectively reversing some of the decline of the immune system with age - this adds weight to the evidence for immune rejuvenation through selective destruction of errant cells.

I launched Open Cures this year, an effort to do something about the ridiculous state of regulation and medical development of longevity science. It is a project that I need to get back to working on more aggressively as soon as possible; change doesn't make itself happen.

An study showing an unexpected five year effect on human longevity - a good half the expected effect of regular exercise, a magnitude highly unusual for an established medical treatment - came and went largely unremarked.

The Russian side of the longevity science community has continued to build connections with the English-speaking world. The Science for Life Extension Foundation puts out very attractive materials, the Russian cryonics company KrioRus continues to grow, and more data is emerging on mitochondrially targeted antioxidants under development by Vladimir Skulachev's group.

Resveratrol and indeed the whole sirtuin endeavor has fallen out of favor in the last year - looking like yet another dead end to add to the annals of overly optimistic pharmaceutical development. I would expect to see much more of this sort of thing until the research community switches more of their focus to working on SENS program goals. Try to fix the damage, not just dig up drugs that alter metabolism a little bit.

Tissue engineering in 2011 has been a matter of leaps and bounds - too many to mention. There has been pancreas regeneration, more engineered trachea transplants, building of urethras, blood vessels, and mouse teeth. Which is not to mention small intestine sections, decellularized lungs, and the construction of a working sphincter. And more; this is what an energetic, well funded field looks like.

The naked mole rat genome was sequenced earlier in the year. This is a big step forward for the contingent of researchers agitating for the genetic comparison of long-lived mammals. Why are they long-lived? What can we learn? The mole rat genome is doing the rounds, and researchers will refine their present investigations of the species' noteworthy longevity and cancer resistance.

Sonia Arrison published 100+, a book that aimed to introduce many of the topics here at Fight Aging!, and garnered a fair amount of attention from the mainstream.

And of course, a hundred other items that I'm omitting. It's been busy out there - we're slowly edging into the early barnstorming age of longevity science, in which novel ways to extend life in mice are arriving every couple of months and new longevity-related genes are cataloged at a much faster rate. We measure progress by the degree to which people like me stop talking about certain topics or reporting on certain forms of research because they have become commonplace. It's an exciting time, certainly, and shows no signs of slowing down yet.

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

In aging there is a lot of correlation - many biological systems that are traditionally studied separately are declining at once, so most researchers are only looking in detail at one tiny part of aging. Part of the challenging facing researchers has always been how to figure out what is cause and what is consequence given the need for specialization to make progress in any given small area of the biology of aging. Here, researchers focus on the immune system, and you can see the biases inherent in being a specialist: "The aging process is accompanied by an impairment of the physiological systems including the immune system. This system is an excellent indicator of health. We have also observed that several functions of the immune cells are good markers of biological age and predictors of longevity. In agreement with the oxidation-inflammation theory that we have proposed, the chronic oxidative stress that appears with age affects all cells and especially those of the regulatory systems, such as the nervous, endocrine and immune systems and the communication between them. This fact prevents an adequate homeostasis and, therefore, the preservation of health. We have also proposed an involvement of the immune system in the aging process of the organism, concretely in the rate of aging, since there is a relation between the redox state and functional capacity of the immune cells and the longevity of individuals. A confirmation of the central role of the immune system in oxi-inflamm-aging is that several lifestyle strategies such as the administration of adequate amounts of antioxidants in the diet, physical exercise, physical and mental activity through environmental enrichment and hormetic interventions improve functions of immune cells, decreasing their oxidative stress, and consequently increasing the longevity of individuals."

Link: http://www.ncbi.nlm.nih.gov/pubmed/22188449

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

Pulling together the connections in a review paper: "Obesity is a condition in which excess or abnormal fat accumulation may present with adverse effects on health and decreased life expectancy. Increased body weight and adipose tissue accumulation amplifies the risk of developing various age-related diseases, such as cardiovascular disease, Type 2 Diabetes Mellitus, musculoskeletal disorders, respiratory diseases and certain types of cancer. This imbalance in body composition and body weight is now recognized as a state of increased oxidative stress and inflammation for the organism. Increasing oxidative stress and inflammation affect telomeres. Telomeres are specialized DNA-protein structures found at the ends of eukaryotic chromosomes and serve as markers of biological aging rate. They also play a critical role in maintaining genomic integrity and are involved in age-related metabolic dysfunction. Erosion of telomeres is hazardous to healthy cells, as it is a known mechanism of premature cellular senescence and loss of longevity. The association of telomeres and oxidative stress is evident in cultured somatic cells in vitro, where oxidative stress enhances the process of erosion with each cycle of replication. Shorter telomeres have been associated with increasing body mass index, increased adiposity, and more recently with increasing waist to hip ratio and visceral excess fat accumulation. Furthermore, many of the metabolic imbalances of obesity (e.g. glycemic, lipidemic, etc.) give rise to organ dysfunction in a way that resembles the accelerated aging process."

Link: http://www.ncbi.nlm.nih.gov/pubmed/22186032

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

I note a symptom of the highly restrictive FDA regulations on development of clinical therapies:

The indictment alleges the four distributed stem cells and other biological products without federal Food and Drug Administration approval, and for unapproved treatments of cancer, amyotrophic lateral sclerosis, multiple sclerosis, and Parkinson's Disease. ... Court records unsealed Wednesday show that the scheme made more than $1.5 million in sales between January 2007 and April 2010, from procedures Morales performed in Mexico on patients he met in the United States.

This is the standard situation: when regulation makes it impossible to meet demand or to try to develop and offer meaningful products, a black market will arise. That market will be less transparent, more costly, and less effective at delivering quality products than a free market would be in the absence of regulation. A black market will also tend to attract a larger contingent of sellers willing to commit fraud than would otherwise be the case, as the buyers have lower chances of success in any legal action or other means of forcing restitution.

So these fellows may be frauds, or they may be legitimate businesspeople trying to operate a medical tourism business, offering services that are perfectly legal - and even admirable - outside the US, while within the US forthright invention and competition in medicine is pretty much forbidden. Either way, other would-be legitimate businesspeople are going to look at this and think twice about trying to make the world a better place by offering better medical services.

So it goes. The FDA and its legal penumbra are monstrosities that distort all of the usual incentives involving profit and progress, and steer them towards bad ends. The FDA must go if we are to see progress in medicine that approaches the pace of progress in less regulated industries like computing.

There is a very simple solution to the problems of medicine. It's called freedom: freedom for providers to develop and compete as they see fit, and freedom for people to choose or reject their offerings with the money in their own pockets and savings accounts. For progress and efficiency to reign in an industry, people have to pay for goods with their own funds, and providers have to be free to innovate. Competition and the care with which people manage their own money keeps both sides as honest as any human culture is going to be.

Look at fashion. Shoes. Computers. DNA sequencing. Or any one of a thousand other important goods whose value has fallen over time and continues to do so. These are less regulated markets, not stifled and buried beneath chains like the provision of medicine. They are vibrant, constantly innovating and competing, and this is exactly because people pay for these products with the money they care about most.

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

A commentary at the journal Aging: "In the past 15 years, genomics has penetrated all areas of the life sciences, and this dramatic change in the way science is done is often viewed as genome revolution. However, application of genomics to study senescence and aging lagged behind. Until this year, no genomes have been sequenced explicitly to understand aging. In this regard, the recent completion of the genome of the naked mole rat marks an important milestone, as this study was performed primarily to better understand the exceptional longevity of this rodent. Naked mole rats live in the subterranean niche in southeast Africa and are the longest-lived rodents (maximum lifespan of 32 years). Being the size of a mouse, naked mole rats can be conveniently studied in the laboratory setting and compared with other rodents. What have we learned from the initial analysis of the genome of this remarkable animal? First, the genome is characterized by the reduced level of polymorphism, consistent with low DNA mutation rate (although other explanations are also possible). Second, an unusual thermogenesis of naked mole rats, which may be linked to longevity through metabolic rate, is consistent with the altered sequence of a key thermoregulator, UCP1, which modified its sequences that mediate regulation by nucleotides and fatty acids. Another interesting finding is the unique sequence of a tumor suppressor p16, a protein whose mutations were linked to a variety of human diseases associated with aging. In addition, analyses of gene expression as a function of age distinguished naked mole rats from other mammals. ... The availability of the genome of the naked mole rat should be viewed as the first step in the process of understanding of the delayed aging of this mammal, and also as a useful resource for studying the aging process in general. It is clear that much of its value lies in comparison with the genomes of other mammals, both with long and short lifespans, as well as in downstream functional genomic studies that assess genetic and epigenetic regulation networks. Comparative genomics of short-lived and long-lived organisms offers great opportunities to understand evolutionary forces and molecular mechanisms that regulate lifespan."

Link: http://www.impactaging.com/papers/v3/n12/full/100417.html

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

Human studies may reveal a correlation between longevity and lower rates of reproduction: "A number of leading theories of aging, namely The Antagonistic Pleiotropy Theory (Williams, 1957), The Disposable Soma Theory (Kirkwood, 1977) and most recently The Reproductive-Cell Cycle Theory (Bowen and Atwood, 2004, 2010) suggest a tradeoff between longevity and reproduction. While there has been an abundance of data linking longevity with reduced fertility in lower life forms, human data have been conflicting. We assessed this tradeoff in a cohort of genetically and socially homogenous Ashkenazi Jewish centenarians (average age ~100 years). As compared with an Ashkenazi cohort without exceptional longevity, our centenarians had fewer children (2.01 vs 2.53, p<0.0001), were older at first childbirth (28.0 vs 25.6, p<0.0001), and at last childbirth (32.4 vs 30.3, p<0.0001). The smaller number of children was observed for male and female centenarians alike. The lower number of children in both genders together with the pattern of delayed reproductive maturity is suggestive of constitutional factors that might enhance human life span at the expense of reduced reproductive ability."

Link: http://www.impactaging.com/papers/v3/n12/full/100415.html

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