An example of the world moving forward, even though the really flashy biotechnology is still in the laboratory rather than the clinic: "Age-related macular degeneration (AMD) is the most frequent cause of blindness in the Western World. A [report] shows the number of new cases of blindness and severe visual loss in Denmark has been halved during the last ten years. ... [Researchers] examined the records of 11,848 new cases of legal blindness. The rate of blindness from AMD fell from 522 cases per million inhabitants aged 50 years or older in 2000, to 257 cases per million in 2010, a reduction by over 50 per cent. The bulk of the decrease occurred after 2006, following the introduction of new effective treatment for wet AMD, which is characterised by leaking blood vessels having formed under the fovea. The treatment consists of repeated injections into the eye of a medication that inhibits the signalling molecule vascular endothelial growth factor (VEGF). ... The observations from Denmark were published together with a corroborating report from Israel that found comparable changes in the incidence of legal blindness in that country. ... The massive implementation of modern wet AMD therapy has been a challenge. It is therefore very important that we can now show an impact on public health and it is wonderful to see a reduction in severe visual loss."

Link: http://news.ku.dk/all_news/2012/2012.1/danish-report-shows-risk-of-blindness-halved/

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

There are a lot of genes wherein alterations correlate with longevity - either mutations, removal of the gene, or epigenetic variations. Some of these are similar between many species, some restricted to a few small branches of the evolutionary tree. As the costs of investigating the genome and the proteome fall rapidly, ever more data is accumulated on the detailed relationships between biology and longevity at the level of molecular mechanisms.

There really is too much new work emerging to point out every study - it has become unremarkable to discover new correlations in the genetics of longevity. Also, when it comes down to it, little of this research will be of any real relevance to the most direct and important work on rejuvenation biotechnology. The research community knows more than enough to enable work on repairing the damage that causes aging.

In any case, here is a recent and representative selection from the ongoing flood of new results on genetics and longevity:

Reduction of Mitoferrin Results in Abnormal Development and Extended Lifespan in Caenorhabditis elegans

Iron is essential for organisms. It is mainly utilized in mitochondria for biosynthesis of iron-sulfur clusters, hemes and other cofactors. Mitoferrin 1 and mitoferrin 2, two homologues proteins belonging to the mitochondrial solute carrier family, are required for iron delivery into mitochondria. ... In this study we found that reduced mitoferrin levels in C. elegans by RNAi treatment causes pleiotropic phenotypes such as small body size, reduced fecundity, slow movement and increased sensitivity to paraquat. Despite these abnormities, lifespan was increased by 50% to 80% in N2 wild type strain, and in further studies using the RNAi sensitive strain eri-1, more than doubled lifespan was observed. The pathways or mechanisms responsible for the lifespan extension and other phenotypes of mitoferrin RNAi worms are worth further study, which may contribute to our understanding of aging mechanisms and the pathogenesis of iron disorder related diseases.

Activity of mannose-binding lectin (MBL) in centenarians

We analyzed MBL2 gene variants in two cohorts of centenarians, octo- and nonagenarians and in the general population, one from Sardinia island (Italy), recruited in the frame of the AKea study, and another from Campania (southern Italy), to search for haplotypes related to longevity. ...The frequency of high and null activity haplotypes was significantly lower and the frequency of intermediate activity haplotype significantly higher in centenarians and in subjects between 80 and 99 years from both the cohorts as compared each to the general population from the same geographic area.

MICS-1 interacts with mitochondrial ATAD-3 and modulates lifespan in C. elegans

Here, we provide evidence that MICS-1 is an interacting partner of the mitochondrial protein ATAD-3 (homologue of human ATAD3), which is essential for C. elegans development. We demonstrate that [RNA interference of mics-1 causes] enhanced longevity with an increased mean lifespan of up to 54% compared to control animals. Of note, also [RNA interference of atad-3] promoted longevity, although to a lesser extend (29% compared to controls).

Linkage of Cardiac Gene Expression Profiles and ETS2 with Lifespan Variability in Rats

Longevity variability is a common feature of aging in mammals, but the mechanisms responsible for this remain largely unknown. Using microarray datasets [we] identified a set of 252 cardiac transcripts predictive of relative lifespan in [rats]. ... four transcription factors (Max, Ets2, Erg, and Msx2) present in heart displayed longevity-dependent, strain-independent changes in abundance, but only ETS2 had an expression profile that directly correlated with the relative lifespan gene set. ... We conclude that variations in ETS2 abundance in hearts of adult rodents and the associated loss of CMs, contribute at least partially, to the longevity variability observed during normal aging of rats through activation of programmed necrosis.

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

Advanced glycation end-products (AGEs) are implicated in aging - one of the forms of chemical gunk that accumulates in the body over time, harming the operation of intricate biomolecular machinery (in this case probably by triggering cells to respond in an undesirable way). AGEs are a part of our dietary intake as well as being generated in the body, and there is a debate over the degree to which dietary intake of AGEs is important in the pace of buildup over a lifetime - and the role of gut bacteria for that matter, given that they can independently produce AGEs as well. Here is a review paper on the subject: "Advanced glycation end products (AGEs) are a heterogeneous, complex group of compounds that are formed when reducing sugar reacts in a non-enzymatic way with amino acids in proteins and other macromolecules. This occurs both exogenously (in food) and endogenously (in humans) with greater concentrations found in older adults. While higher AGEs occur in both healthy older adults and those with chronic diseases, research is progressing to both quantify AGEs in food and in people, and to identify mechanisms that would explain why some human tissues are damaged, and others are not. In the last twenty years, there has been increased evidence that AGEs could be implicated in the development of chronic degenerative diseases of aging, such as cardiovascular disease, Alzheimer's disease and with complications of diabetes mellitus. Results of several studies in animal models and humans show that the restriction of dietary AGEs has positive effects on wound healing, insulin resistance and cardiovascular diseases. Recently, the effect of restriction in AGEs intake has been reported to increase the lifespan in animal models. This paper will summarize the work that has been published for both food AGEs and in vivo AGEs and their relation with aging, as well as provide suggestions for future research."

Link: http://www.ncbi.nlm.nih.gov/pubmed/22254007

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

A brief overview of one of the lines of work advocated by the Science for Life Extension Foundation: "Aging biomarkers are parameters that always, and in all people, change during aging. It is possible to evaluate and improve therapies that are aimed at slowing down aging, using the biomarkers of aging. The value and changing dynamics of aging markers provides information about the intensity of aging processes in the cells of the patient. Aging biomarker monitoring allows us not only to diagnose various diseases, but also to prevent their development. Aging can be slowed down. At the moment, there are already several scientific approaches that could lead to slowing down aging, and extending life. Scientists have been able to significantly extend the lifespans of model animals. Now, it is time to apply the biogerontology knowledge in clinical practice. To understand if a given therapy is effective or not, first of all we compile data via conventional clinical tests to create the 'electronic health passport.' After that, we can perform measurements of the aging biomarkers listed in the table. The indicators will inform us if the therapy is working. Soon we will be able to look at thousands of parameters, obtained using genome and transcriptome sequencing, epigenome mapping and analysis of proteome and metabolome. The additional data will make the anti-aging therapies more precise. ... view our entire booklet that lists twenty (20) aging bio-markers."

Link: http://ieet.org/index.php/IEET/more/konovalenko20120118

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

I'm not a big fan of the optimization mindset when it comes to long term health and longevity. Like all forms of optimization, it makes for a great hobby - with the potential to turn into a massive sink of time and money if you head on all the way down the rabbit hole. Importantly, however, and unlike optimization hobbies that involve cars, games, and other easily measured items, you will never really know how well you are doing when it comes to your own life expectancy. It's extremely easy to get the 80/20 result: practice calorie restriction and exercise regularly. But beyond that, there's no real way to tell whether any of your more esoteric practices are helping, hindering, or doing more or less nothing. There is no meaningful scorecard for future remaining life expectancy that you can measure and check your optimization efforts against.

This may well change over the next ten years, but for now it is what it is. By all means make health your hobby - it beats some of the other options in terms of general utility - but don't for one moment imagine that you actually know how well you're doing past the 80/20 point. And if you're not practicing calorie restriction, then it doesn't much matter what else you're doing because you haven't even captured all of the easy 80%.

Anyway, that all said, here is an interesting article that looks at measuring risk and life expectancy at the small scale - which is often a prelude to optimization, given human nature.

Many risks we take don't kill you straight away: think of all the lifestyle frailties we get warned about, such as smoking, drinking, eating badly, not exercising and so on. The microlife aims to make all these chronic risks comparable by showing how much life we lose on average when we're exposed to them: a microlife is 30 minutes off your life expectancy

Life expectancy for a man aged 22 in the UK is currently about 79 years, which is an extra 57 years, or 20,800 days, or 500,000 hours, or 1 million half hours. So, a young man of 22 typically has 1,000,000 half-hours (57 years) ahead of him, the same as a 26 year-old woman. We define a microlife as a chronic risk that shortens life on average by just one of the million half hours that they have left.

Here are some things that would, on average, cost a 30-year-old man 1 microlife:

Smoking 2 cigarettes

Drinking 7 units of alcohol (eg 2 pints of strong beer)

Each day of being 5 Kg overweight

A chest X-ray will set a middle-aged person back around 2 microlives, while a whole body CT-scan would weigh in at around 180 microlives.

This falls under the general heading of "fun with population-wide statistical measures of mortality," but you should find it food for thought, even if not of immediate application. On that note, an interesting speculative calculation to run, or at least build a framework for, would be a guesstimation of the benefit in microlives gained per dollar donated to the SENS Foundation.

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

An interview with Aubrey de Grey of the SENS Foundation: "I'm interested in making sure that none of [the forms of biological damage that cause aging] are left behind. ... the main reason why we prioritize certain things over others is simply if they are not being prioritized by the rest of the world. At the moment, [in] our Research Center in Mountain View, we are working on LysoSENS, as you said, but we are also working on MitoSENS, the elimination of mitochondrial mutations in aging, and ways to make those mitochondrial mutations harmless essentially by putting copies of the mitochondrial genome into the nuclear genome. And in projects that we are funding in university labs around the country, we are doing a number of other things relating to other aspects of SENS. So yes, we are interested in focusing on all of these things in parallel. ... So at the moment, there are just a few areas within SENS that we are de-prioritizing because they are being funded quite well elsewhere. One of them is the elimination of amyloids [that] occurs in Alzheimer's disease. And even there, it's only sort of that one subset of that one deadly thing that we are not working on. So we are working on something very similar, the accumulation of a similar type of garbage outside cells that occurs predominantly in the heart. It just turns out that even though Alzheimer's work is well-funded and well respected and everything, nevertheless during the same sort of approach for other types of amyloids, other types of extracellular garbage, it is not being particularly enthusiastically pursued by other people, so we are doing our bit. Similarly, in the case of lost cells where cells die and they are not automatically replaced by other cells or by the division of other cells - that is what stem cells are for. Stem cell therapy is very real - people are working in lots of areas in that field, so of course we are not trying to duplicate that effort. But even there, we are doing one of two things. For example, we're interested in a particular type of cell loss which is the shrinkage of an organ called the thymus, which is responsible for the creation of certain types of immune cells. It turns out that restoration of the thymus to its useful size is something that not many people work on. The approaches that have been tried have not been very successful. We are looking at some more ambitious but we think more promising approaches that have not been looked at by other people."

Link: http://hplusmagazine.com/2012/01/17/progress-in-therapies-for-rejuvenation-and-their-delivery/

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

Another telomere length correlation, adding data to a relationship known for some years: "A process linked to natural cell aging has now also been associated with knee osteoarthritis, researchers say. Telomeres - lengths of DNA on the ends of chromosomes, sometimes described as being like the plastic cap on a shoelace tip - naturally shorten with age, but can also shorten due to sudden cell damage. Abnormally short telomeres have been found in some types of cancer and preliminary research has suggested that the average telomere length is also shortened in osteoarthritis. In this new study, Danish researchers used new technology to closely examine the telomeres of cells taken from the knees of osteoarthritis patients who had joint replacement surgery. The cells had abnormally shorted telomeres and the percentage of cells with ultra-short telomeres increased with proximity to the damaged area in the knee joint ... The telomere story shows us that there are, in theory, two processes going on in osteoarthritis. Age-related shortening of telomeres, which leads to the inability of cells to continue dividing and so to cell senescence [deterioration], and ultra-short telomeres, probably caused by compression stress during use, which lead to senescence and failure of the joint to repair itself. We believe the second situation to be the most important in osteoarthritis. The damaged cartilage could add to the mechanical stress within the joint and so cause a feedback cycle driving the progression of the disease."

Link: http://health.usnews.com/health-news/family-health/pain/articles/2012/01/17/knee-arthritis-may-speed-up-process-linked-to-cell-aging

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