I've noted work on correlations between air pollution and reduced life expectancy in past years; the statistical differences are usually very small in comparison to what you can do for yourself via calorie restriction and exercise, as air pollution in wealthier regions of the world is a fraction of what it was a century past. As populations became radically richer in the course of the past three centuries, the luxury of being able to pay for a better environment became possible - either directly or through investment in technologies that cause less pollution in the course of achieving their end goals. It wasn't all that long ago, for example, that there were dead rivers in the US and Western Europe. Those rivers would still be dead if not for the fact that our societies are far wealthier than those of our grandparents; to be able to be an environmentalist is very much a luxury. It requires sufficient surrounding wealth or knowledge to be able to do things a different way.

In any case, here is a recent study on air quality and life expectancy in China - a region of the world that is still largely an expanse of 20th-century styled comparative poverty, scattered with enclaves and belts of modern wealth.

Air Pollution Shortens Life Expectancy and Health Expectancy for Older Adults: The Case of China.

Outdoor air pollution is one of the most worrying environmental threats China faces today. Comprehensive and quantitative analyses of the health consequences of air pollution in China are lacking. This study reports age- and sex-specific life expectancy and health expectancies (HEs) corresponding to different levels of air pollution based on associations between air pollution and individual risks for a host of health conditions and mortality net of individual- and community-level confounders.

...

The main outcome measures in this study include life expectancy estimated from mortality and HEs based on five health conditions including activity of daily living, instrumental activity of daily living, cognitive status, self-rated health, and chronic conditions. Net of the controls, exposure to outdoor air pollution corresponded to subsequent reductions of life expectancy and HEs for all five health conditions. These detrimental pollution effects were stronger for women. The gap in life expectancy between areas with good air quality and moderately heavily polluted areas was 3.78 years for women of age 65 and 0.93 years for men. The differences in HEs at age 65 were also large, ranging from 1.47 years for HE for good self-rated health in men to 5.20 years for activity of daily living disability-free HE in women.

Air quality tends to be mixed up with a range of other confounding factors, however. This requires careful work on the part of researchers to have a chance of teasing out air quality effects independently of other factors that lead people to remain in areas of poor air quality:

I would be willing to wager that the correlation has more to do with the relative wealth of these areas and those who make the economic choice to live there, as well as access to medical technology and lifestyle choices. Things are rarely as simple as a two-parameter study casts them to be.

Still, aging is damage, and there's do great doubt that very polluted air does damage people over the long term, to a degree related to the level of pollution: inflammation, increased risk of age-related disease, outright lung damage, risk of cancer, that sort of thing. But once the air becomes clean enough for effects to be subtle - meaning much less in magnitude that effects of exercise, differences in wealth, intelligence, or even state of mind - then attention should turn to other controllable factors in life.

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

This seems like an interesting marker of public awareness of aging science; one of the noted researchers in the field recently started on a biweekly column for a local paper. Links to the columns published to date can be found on this page: "In my last column I discussed something we all know intuitively: Generally speaking, larger species of animals live longer than smaller species and this pattern extends even to whales that live more than 200 years. Are there dramatic exceptions to this rule - like people, for instance? Think of other mammals about our size, such as deer or mountain lions or seals. Don't we live longer than they do? The answer is, 'Yes, we do.' Humans live about five times as long as the average mammal of the same size, which makes us pretty special - but not as special as bats. Texas is bat country, as anyone who has watched millions of bats boil out of Bracken Cave or from under Austin's Congress Avenue Bridge can verify. What many people don't realize is how long bats live. For their size, bats are the longest-lived mammals by far, living up to 10 times as long as an average mammal of similar size. ... Think about this for a second. Your dog or cat, eating the best food science can provide, protected from predators and the elements and vaccinated against all sorts of diseases, is doing well to reach 15 to 20 years of age. By comparison, in order for a bat in the wild to survive it must catch its own prey, elude predators, resist climatic extremes, and avoid a wide range of infectious diseases. Yet despite these challenges, bats can live twice as long as your pampered pet." Current thinking on bat longevity looks to be similar to theories on naked mole rat longevity - it has to do with resistance of cell membranes (and especially mitochondria) to oxidative damage, otherwise known as the membrane pacemaker hypothesis of aging. This is thought to have developed in bats, and in birds, in respond to the metabolic demands of flight.

Link: http://barshop.uthscsa.edu/main/newsseminars/news/u50

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

Damage to mitochondrial DNA contributes to aging, and mitochondrial function is in general influential upon aging - damage causes harm by preventing the production of protein machinery vital to mitochondrial activity, which is the start of a long process that sees cells overtaken by dysfunctional mitochondria, and exporting their dysfunction to surrounding tissue by emitting harmful reactive molecules. There are numerous different sorts of DNA damage, however. Point mutations, for example, have been shown to do little to aging. Deletions, where whole reaches of DNA are knocked out, are a different story, and here researchers are investigating how this form of DNA damage varies between species: "Deletion mutations within mitochondrial DNA (mtDNA) have been implicated in degenerative and aging related conditions, such as sarcopenia and neuro-degeneration. While the precise molecular mechanism of deletion formation in mtDNA is still not completely understood, genome motifs such as direct repeat (DR) and stem-loop (SL) have been observed in the neighborhood of deletion breakpoints and thus have been postulated to take part in mutagenesis. In this study, we have analyzed the mitochondrial genomes from four different mammals: human, rhesus monkey, mouse and rat ... Our analysis revealed that in the four species, DR and SL structures are abundant and that their distributions in mtDNA are not statistically different from randomized sequences. However, the average distance between the reported age associated mtDNA breakpoints and their respective nearest DR motifs is significantly shorter than what is expected of random chance in human and rhesus monkey, but not in mouse and rat, indicating the existence of species specific difference in the relationship between DR motifs and deletion breakpoints. In addition, the frequencies of large DRs tend to decrease with increasing lifespan among the four mammals studied here, further suggesting an evolutionary selection against stable mtDNA misalignments associated with long DRs in long-living animals."

Link: http://dx.doi.org/10.1371/journal.pone.0035271

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

The latest issue of the open access journal Immunity & Aging includes a number of interesting papers covering the overlap between genetic contributions to natural variations in longevity and the aging of the immune system - which contributes to a range of age-related dysfunction and systems failure. They are very much in the mainstream model of narrow, unambitious, cautious vision: aiming for and expecting only modest, gradual improvements in health and longevity. Even in this time of radical change in biotechnology, the old habits of incrementalism and understatement regarding the bounds of the possible for human longevity are only slowly fading. The future must be one of ambitious, grand visions in medical science and funding for research if we are to benefit fully from the true potential of biotechnology. In any case, these papers remain interesting for what they are, and are available as provisional PDFs at this time - the download links are on the abstract pages below.

"Positive biology": the centenarian lesson:

The extraordinary increase of the elderly in developed countries underscore the importance of studies on ageing and longevity and the need for the prompt spread of knowledge about ageing in order to satisfactorily decrease the medical, economic and social problems associated to advancing years, because of the increased number of individuals not autonomous and affected by invalidating pathologies. Centenarians are equipped to reach the extreme limits of human life span and, most importantly, to show relatively good health, being able to perform their routine daily life and to escape fatal age-related diseases. Thus, they are the best example of extreme longevity, representing selected people in which the appearance of major age-related diseases, such as cancer, and cardiovascular diseases among others, has been consistently delayed or escaped. ... The aim is to realize, through a "positive biology" approach (rather than making diseases the central focus of research, "positive biology" seeks to understand the causes of positive phenotypes, trying to explain the biological mechanisms of health and well-being) how to prevent and/or reduce elderly frailty and disability.

Epidemiological, genetic and epigenetic aspects of the research on healthy ageing and longevity:

In this article we aimed to overview the research on the biological basis of human healthy ageing and longevity, discussing the role of epidemiological, genetic and epigenetic factors in the variation of quality of ageing and lifespan, including the most promising candidate genes investigated so far. Moreover, we reported the methodologies applied for their identification, discussing advantages and disadvantages of the different approaches and possible solutions that can be taken to overcome them.

Genetics of longevity. Data from the studies on Sicilian centenarians:

Scientists have focused their attention on centenarians as optimal model to address the biological mechanisms of "successful and unsuccessful ageing". They are equipped to reach the extreme limits of human life span and, most importantly, to show relatively good health, being able to perform their routine daily life and to escape fatal age-related diseases, such as cardiovascular diseases and cancer. Thus, particular attention has been centered on their genetic background and immune system. In this review, we report our data gathered for over 10 years in Sicilian centenarians. Based on results obtained, we suggest longevity as the result of an optimal performance of immune system and an over-expression of anti-inflammatory sequence variants of immune/inflammatory genes.

Extending healthy ageing: nutrient sensitive pathway and centenarian population:

To increase our understanding of how ageing works, it may be advantageous to analyze the phenotype of centenarians, perhaps one of the best examples of successful ageing. Healthy ageing involves the interaction between genes, the environment, and lifestyle factors, particularly diet. Besides evaluating specific gene-environment interactions in relation to exceptional longevity, it is important to focus attention on modifiable lifestyle factors such as diet and nutrition to achieve extension of health span. Furthermore, a better understanding of human longevity may assist in the design of strategies to extend the duration of optimal human health.

The application of genetics approaches to the study of exceptional longevity in humans: potential and limitations:

The average life-span of the population of industrialized countries has improved enormously over the last decades. Despite evidence pointing to the role of food intake in modulating life-span, exceptional longevity is still considered primarily an inheritable trait, as pointed out by the description of families with centenarian clusters and by the elevated relative probability of siblings of centenarians to become centenarians themselves. However, rather than being two separate concepts, the genetic origin of exceptional longevity and the more recently observed environment-driven increase in the average age of the population could possibly be explained by the same genetic variants and environmentally modulated mechanisms (caloric restriction, specific nutrients). In support of this hypothesis, polymorphisms selected for in the centenarian population as a consequence of demographic pressure have been found to modulate cellular signals controlled also by caloric restriction.

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

Via ScienceDaily: researchers "have identified a group of 'aging' genes that are switched on and off by natural mechanisms called epigenetic factors, influencing the rate of healthy aging and potential longevity. The study also suggests these epigenetic processes - that can be caused by external factors such as diet, lifestyle and environment - are likely to be initiated from an early age and continue through a person's life. The researchers say that the epigenetic changes they have identified could be used as potential 'markers' of biological aging and in the future could be possible targets for anti-aging therapies. ... the study looked at 172 twins aged 32 to 80 from the TwinsUK cohort. The researchers looked for epigenetic changes in the twins' DNA, and performed epigenome-wide association scans to analyze these changes in relation to chronological age. They identified 490 age related epigenetic changes. They also analysed DNA modifications in age related traits and found that epigenetic changes in four genes relate to cholesterol, lung function and maternal longevity. To try to identify when these epigenetic changes may be triggered, the researchers replicated the study in 44 younger twins, aged 22 to 61, and found that many of the 490 age related epigenetic changes were also present in this younger group. The researchers say these results suggest that while many age related epigenetic changes happen naturally with age throughout a person's life, a proportion of these changes may be initiated early in life."

Link: http://www.sciencedaily.com/releases/2012/04/120419191709.htm

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

An open access review paper looks at how the study of fly aging has informed the life sciences: "it is likely that not all senescent physiological changes revealed in flies can be simply translated to humans. However, flies and humans often show very similar age-related physiological phenotypes suggesting that at least some of the basic biological properties and mechanisms that regulate longevity are conserved amongst species. ... It is well-known that advances in medicine and health care have significantly contributed to increased longevity in humans over the last 100 years. There is also a clear trend toward increased life expectancy including an increase in the numbers of people living to an advanced age and the number of people with chronic age-related diseases. These trends emphasize the need to understand the genetic and physiological factors underlying biological aging and particularly, those that promote healthy aging. ... there are three ways to extend lifespan: increasing early survival rate, increasing late survival rate, or delaying senescence. Remarkably, the first two do not affect basic aging processes. For example, the first one leads to a significant increase in mean but not maximum lifespan, while the second one leads to change in a maximum but not mean lifespan. Delayed senescence, in turn, leads to a significant increase in both the mean and maximum lifespan. ... This raises the question as to whether healthspan and delayed senescence are inter related. As stated above, while many genes have been shown to extend lifespan, these may have little or no ability to delay physiological senescence. In other words, the period of functional disability before death may increase despite the fact that the total duration of life is increased. Thus, the search for appropriate biomarkers applicable to monitor functional senescence is highly important with regards to healthy aging and age-related diseases." These cautions are very much focused on the mainstream research goals of slowing the rate of aging through genetic and metabolic alterations; they have little relevance to efforts aimed at producing continuous repair of aging.

Link: http://www.frontiersin.org/Integrative_Physiology/10.3389/fphys.2012.00106/full

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

The employees and appointees of the US Food and Drug Administration have caused an incredible destruction of value and progress over the time that the agency has existed. Their regulatory policies become ever more onerous with each passing year, as unaccountable bureaucrats follow their incentives: nothing good can happen to their careers as a result of approving new technologies, and nothing bad tends to happen to their careers as a result of making it really, really hard to bring new medicine to the clinic. So of course you wind up with an organization whose members collectively pay nothing more than lip service to their declared mission, while working to make sure that medicine stays moribund in a slow-motion stasis. This is most evident in the cancer research community, largely because of its size, but it applies just as evenly across all forms of medicine:

A 2010 study in the Journal of Clinical Oncology by researchers from the M.D. Anderson Cancer Center in Houston, Texas found that the time from drug discovery to marketing increased from eight years in 1960 to 12 to 15 years in 2010. Five years of this increase results from new regulations boosting the lengths and costs of clinical trials. The regulators aim to prevent cancer patients from dying from toxic new drugs. However, the cancer researchers calculate that the delays caused by requirements for lengthier trials have instead resulted in the loss of 300,000 patient life-years while saving only 16 life-years.

To add to this picture, you must also see incumbent Big Pharma entities and their executives and lobbyists - a deeply enmeshed network of regulatory capture. They are far more willing to use the current system as a weapon to suppress disruptive innovation in their industry than to be a source of innovation themselves. So it goes, just as in any other heavily regulated market. The strategic goals of the major players wind up having very little to do with creating beneficial change, and everything to do with keeping things the same as they are now.

As I've said in the past, it is a waste of energy to fight this. That's a money pit, and resources are better spent on creating actual progress than lining the pockets of politicians, their lackeys, and other corrupt cogs in the system. Work around the roadblock instead: start companies and partner for research development outside the US. Deliver services in Asia and take advantage of cheap flights and the growing medical tourism industry. The only way that the FDA will whither away is to make it entirely irrelevant - and as the bureaucrats keep piling on the costs, erecting an ever higher barrier to actually developing any new medicine in the US, that will become a more popular option. You can be sure that the wealthier and more connected individuals who make regulations and advocate for ever greater powers to accrue to the FDA will be amongst the first flying beyond the US to undergo newer therapies - treatments that they have managed to make illegal or too expensive to exist in their own country.

Some more on this topic:

Though the United States urgently needs new treatments for common illnesses such as heart disease, stroke, and diabetes, the nation's system for drug approval discourages innovation and investment, especially for our most pressing public health challenges. In this paper, we find that the main culprit is the high cost of Phase III clinical trials, which are required for FDA approval of most drugs. We examined drug development in four major public health areas and discovered that for any given drug on the market, typically 90 percent or more of that drug's development costs are incurred in Phase III trials. These costs have skyrocketed in recent years, exacerbating an already serious problem.

The enormous cost and risk of Phase III trials create incentives for researchers and investors to avoid work on medications for the chronic conditions and illnesses that pose the greatest threat to Americans, in terms of health spending and in terms of the number of people affected. This avoidance, in turn, harms overall U.S. health outcomes and drives up the cost of health care.

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

Following on from research into the mechanisms of rapamycin released earlier this month, here is more on the way it might generate its benefits to longevity in laboratory mammals: "Balancing quiescence with proliferation is of paramount importance for adult stem cells in order to avoid hyperproliferation and cell depletion. In some models, stem cell exhaustion may be reversed with the drug rapamycin, which was shown can suppress cellular senescence in vitro and extend lifespan in animals. We hypothesized that rapamycin increases the expression of oxidative stress response genes in adult stem cells, and that these gene activities diminish with age. To test our hypothesis, we exposed mice to rapamycin and then examined the transcriptome of their spermatogonial stem cells (SSCs). Gene expression microarray analysis revealed that numerous oxidative stress response genes were upregulated upon rapamycin treatment ... When we examined the expression of these genes in 55-week-old wild type SSCs, their levels were significantly reduced compared to 3-week-old SSCs, suggesting that their downregulation is coincident with the aging process in adult stem cells. We conclude that rapamycin-induced stimulation of oxidative stress response genes may promote cellular longevity in SSCs, while a decline in gene expression in aged stem cells could reflect the SSCs' diminished potential to alleviate oxidative stress, a hallmark of aging."

Link: http://impactaging.com/papers/v4/n4/full/100451.html

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

Age-related diseases are among the more visible signs of accumulated biological damage that occurs over time - aging is damage. So we should expect to see less of all such conditions in longer lived populations, and here researchers demonstrate that point for osteoarthritis: "Previous studies have reported that centenarians escape the major age-related diseases. No studies on prevalence and severity of osteoarthritis (OA) in longevity population have previously been reported. Because OA is associated with morbidity and mortality, we hypothesized that radiographic hand OA would generally be less prevalent and would develop at a later age in longevity populations vs non-longevity populations. ... Longevity index was calculated as a ratio of the number of individuals aged [greater than] 90 years vs the number of people aged [greater than] 60, expressed per mil. A population with longevity index [greater than] 40 was considered as a longevity population. ... A significant difference in age standardized prevalence of hand OA was found between each pair of studied samples ... We observed that the pattern of radiographic hand OA in longevity populations differs from the pattern in non-longevity populations. On average, first joints with OA appear at an older age, and progression of hand OA [is] slower."

Link: http://www.ncbi.nlm.nih.gov/pubmed/22526078

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

The 2nd International Conference on the Genetics of Aging and Longevity is presently underway in Moscow, organized by the active Russian arm of the longevity research community - such as the folk behind the Science for Life Extension Foundation - and well-attended by notable life science researchers from around the world. Earlier this month, the Moscow News ran an interview with Michael Batin, one of the organizers. His views are representative of the Russian community, whose members tend to be forthright and direct when it comes to the end goals of longevity science: to defeat aging entirely, banish the suffering it causes, and usher in an era of ageless humans. More power to them - we could do with a lot more of that sort of outspoken advocacy here in the Anglosphere.

The quoted passages below are run through Google's automated translation engine, which unfortunately still butchers Russian:

Q: What is the real goal that we set ourselves right now? Can you say, talk about extending the life of ten years from now?

MB: In ten years? It is not even present, and yesterday. It has long been proven that reducing caloric intake [and even] just a healthy lifestyle [lead to a longer life]. Our goal is different - a victory over an aging, it is by and large the whole purpose of medical science. After all, if you think about all of the doctors [dedicated to the] prolongation of life, the estrangement of death. A person does not want to die right now, well, anti-aging does not differ fundamentally, it is also the struggle with death.

Q: So you're talking about immortality?

MB: Yes. This is the ultimate goal. In the coming ten years, you can raise the life expectancy [to] 150 years, with adequate [resources and large enough research community]. If, for example, to do research megaproject like the American lunar program. And if we know in ten years that will live more than a hundred years, this will give us more time to find a way to further extend [life].

Q: But how? Are there any pills?

MB: If you're talking about a miracle pill, then, of course not. Aging depends on many factors, and is now the main problem is just that we do not know them all. And the proposed mega-project just involves a systematic search for the causes of aging.

...

Q: And it's all in the mega-project? [It's] going to cost [a] quite impossibly high sum.

MB: But now we are spending huge amounts of money on arms - you've seen defense spending in Russia? - And do not invest in [biogerontology], fundamental research on the causes of aging. Even in the U.S., [where] gerontology takes a billion dollars, [that is] their total spending, of that billion is spent on Alzheimer's disease, [on] geriatrics, and [only a small fraction of it on] the fundamental work on finding the root causes of aging.

Research is always the red-haired stepchild of human endeavors, small and neglected behind the bread, circuses, and cathedrals of destruction. But what can one person do about that? Best not to be too weighed down by the essential insanity of the human condition as we have collectively managed to engineer it. It won't actually require more than a few tens of millions of people to decide they want to make a difference and devote some modest effort towards doing something about aging - a community that large, distributed around the world, could assemble the necessary funds and researchers to, for example, complete the SENS project to demonstrate robust rejuvenation in mice. Everyone else can go on building bombs and monuments if they so desire, but the things that matter will still get done, as they have always done, by a motivated tiny minority.

Long after the time in which anyone can easily recall who was US president in 2011, or what party was in power, or which wars of declining empire were fought, and then long after anyone even cares about that ancient history, and later, long after the whole downward slope of the history of the US is but a footnote of interest to scholars of the transition from second to third millennium, and later still, long after anyone can even find out with any great reliability who was US president in 2011 ... long after all these things are forgotten, the first half of the 21st century will still be clearly recalled as the dawn of the era in which aging was conquered.

Progress in science and technology is really the only thing that matters in the long term.

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