The activity and changing configuration of the immune system is intimately connected with aging in a number of ways. In early life, exposure to infections that require an energetic immune response in effect burns your candle faster by generating more biochemical damage to your body in the process of defending it from the effects of disease. In later life, when the immune system runs beyond its evolutionary warranty, it falls into a state of constant, futile activation and damage - and that damage also adds up.

When you look at the reliability theory of aging, or any like consideration of aging as the consequences of accumulating damage to a complex system, it becomes clear that the immune system is an important component in the model. For example, it is generally accepted that much of the improvement in life expectancy over past centuries stems from a reduction in infectious disease - a process that is by no means complete, given what we still suffer from quiet, persistent infections like cytomegalovirus. But fewer infections mean less activation of the immune system in early life and less damage carried into later life. That leads to both improved health, a physiologically younger body at a given chronological age - and an immune system that declines more slowly, and later in life.

Here is an open access paper in which researchers directly demonstrate (in insects) the principle that early immune activity means a shorter life expectancy:

The pathology of many of the world's most important infectious diseases is caused by the immune response. Additionally age-related disease is often attributed to inflammatory responses. Consequently a reduction in infections and hence inflammation early in life has been hypothesized to explain the rise in lifespan in industrialized societies.

Here we demonstrate experimentally for the first time that eliciting an immune response early in life accelerates ageing. We use the beetle Tenebrio molitor as an inflammation model. We provide a proof of principle for the effects of early infection on morbidity late in life and demonstrate a long-lasting cost of immunopathology.

Like many investigations into the roots of aging, this is more a pointer towards areas where future development of rejuvenation biotechnology should focus than something of direct and immediate use. Results like this add more weight to work on reversing damage in the immune system, and preventing the immune system from falling into a chronic inflammatory state. There isn't anything we can do about our past exposure to infection and persistent agents like cytomegalovirus, but we can help to accelerate the development of ways to fix the resulting damage that we carry with us.

The BBC here looks briefly at the study of aging in varying animal species - it mangles the scientific details in the usual fashion, but covers much of the territory: "From the moment they are born into the dense jungle of Central Africa, the biological clock is ticking for baby bonobos. A recent study, published in the journal Science, revealed that all primates - from men to monkeys - roughly age in the same way, with a high risk of dying in infancy, a low risk of dying as juveniles and then an increasing risk of dying as they aged. Some species though, have found a few tricks to help them play the aging game and extend their natural lifespans. By doing so, they can live for hundreds of years. While a select few, by some definitions, may already have become immortal. ... some species of bat [can] live for decades [and] the explanation may lie in the way bats protect themselves from protein damage, using special molecules called protein chaperones. ... Studies of the American lobster (Homarus americanus), have shown that its extreme longevity might be related to the expression of telomerase ... High concentrations of telomerase are found in cells that need to divide regularly such as organs and embryonic stem cells. Access to an elevated supply of telomerase would equip this crustacean with the ability to rebuild cells damaged by aging. The ability to repair cells in this way may help to explain why lobsters can live up to 100 years and are able to regrow limbs even at an 'old age'. ... Another oceanic resident, the quahog clam (Arctica islandica), is thought to be one of the longest lived metazoans of all. A recent study on this ancient clam, [which] lives more than 400 years, shows it has an increased resistance to oxidative stress. ... The reasons for the exceptional longevity in Arctica may have little to do with resistance to oxidative stress though. ... Instead, like in naked mole rats, it may be the integrity of the animal's proteins that may be the key, rather than damaging free radicals or antioxidants used to defend against them."

Link: http://www.bbc.co.uk/nature/12733853

An example of the how advances in biotechnology are allowing medicine to move closer towards intervening in first causes at the biochemical level: researchers "have developed a new approach for identifying the 'self' proteins targeted in autoimmune diseases such as multiple sclerosis, diabetes and rheumatoid arthritis. ... errant immune responses which mistakenly target the body's own proteins rather than foreign invaders can now be examined in molecular detail. Further research could lead to new insights into the exact causes of these debilitating autoimmune disorders. ... The immune system, the body's main line of defense against disease, has a critical responsibility to distinguish self-derived proteins from those of invaders like viruses and bacteria. Autoimmune diseases arise when a person's immune system fails to make that critical distinction and mistakenly attacks a normal tissue, such as nerve, joint, or insulin-producing pancreatic cells. ... Knowledge of the self-antigens involved in autoimmune processes is important not only for understanding disease etiology, but also for developing diagnostic tests. In addition, physicians may someday use antigen-specific therapies to destroy or disable auto-reactive immune cells. ... But looking through the haystack of cellular complexity for those single-needle self-antigens targeted by the immune system has proved daunting, to say the least. Ideally, scientists would be to develop some kind of biological magnet that could pull these fine needles out of the mass. In this report, the researchers describe an approach which does just that."

Link: http://www.eurekalert.org/pub_releases/2011-06/hms-apn060211.php

Aging research is the poor cousin of the life science field, despite the fact that the overwhelming majority of the harm brought to humanity through disease, frailty, and death is basically caused by aging. Work on extending life or reversing aging is in turn the poor cousin in the aging research family. This situation must change for the better if we are to see meaningful progress in our lifetimes.

A recent article puts some numbers to the picture, here for the Buck Institute, which is one of the largest mainstream laboratories specializing in aging research.

In this fiscal year, the institute will receive about $23 million in government grants, about 66 percent of its $35 million budget. The institute will also get about $5.6 million from the Marin Community Foundation - down from close to $8 million before the economic downturn - and about $5 million from individual and corporate donations.

Compare that with the SENS Foundation, which is currently running a with a yearly budget of a little over $1 million, and is completely reliant on philanthropic donations.

These are small numbers when considered against the broader field of medical research and development. They reflect a society that has not yet woken up to decide that repair of aging is in fact both a possibility and a priority. The feedback loop of education from scientists to the public and support from the public to scientists isn't yet running well for longevity science - it is running better than it was a decade ago, but clearly there is much work to be done.

From the SENS Foundation: "For Max, working at the [SENS Foundation Research Center (SENSF-RC)] has been the culmination of years of dedicated study and preparation. Before he first heard about SENS in early 2005, he wasn't a scientist at all; in fact, he was a 23-year-old cost accountant. When he wasn't studying for his MBA, he was counting other people's money. He knew that he wanted more out of life, though: specifically, he wanted to change the world in a way that would benefit society. As soon as he found and read Aubrey de Grey's Ending Aging, he settled on human health as the area he would strive to impact - and on SENS as the way to make that impact. Over the next few years he committed himself to working in finance, at one point teaching at a local community college, always with the intention of saving his money so that he could return to school to learn about science and laboratory work. During this period he studied whenever he had the time, reading articles relevant to health and aging in scientific journals. In 2008, Max went back to school full-time at the University of Toledo to study chemistry, math, and biology. He was interested in taking an active role in SENS research as quickly as he could, so he contacted the predecessor of the SENS Foundation Academic Initiative, MFURI. As a member of the Initiative, he performed a literature review on the harm caused by iron and aluminum accumulation in the body, citing well over a hundred journal articles. Max's paper was accepted by the journal Rejuvenation Research and published in April 2010, just as he was completing his coursework at Toledo. As his next step, Max opted to join the RC staff rather than pursue a PhD opportunity so that he could continue to make as direct and immediate of a contribution to SENS as possible. Max has now been working at the SENSF-RC for one year, and will be staying on to continue his work on the A2E degradation project. In the long term, he hopes to see the LysoSENS project through all of its pre-clinical stages. It is his wish that this work will lead to therapies that can effectively reverse, or at the least greatly slow, the pathology of age-related macular degeneration."

Link: http://www.sens.org/node/2036

An interesting discovery: "Reprogramming of somatic cells to a pluripotent state was first accomplished using retroviral vectors for transient expression of pluripotency-associated transcription factors. This seminal work was followed by numerous studies reporting alternative (non-insertional) reprogramming methods, and various conditions to improve the efficiency of reprogramming. These studies have contributed little to an understanding of global mechanisms underlying reprogramming efficiency. Here we report that inhibition of the mTOR (mammalian target of rapamycin) pathway by rapamycin or PP242 enhances the efficiency of reprogramming to induced pluripotent stem cells (iPSCs). Inhibition of the insulin/IGF-1 signaling pathway, which like mTOR is involved in control of longevity, also enhances reprogramming efficiency. In addition the small molecules used to inhibit these pathways also significantly improved longevity in Drosophila melanogaster. We further tested the potential effects of six other longevity-promoting compounds on iPSC induction, including two sirtuin activators (resveratrol and fisetin), an autophagy inducer (spermidine), a PI3K (phosphoinositide 3-kinase) inhibitor (LY294002), an antioxidant (curcumin) and an AMPK (activating adenosine monophosphate-activated protein kinase) activator (metformin). With the exception of metformin, all of these chemicals promoted somatic cell reprogramming, though to different extents. Our results show that the controllers of somatic cell reprogramming and organismal lifespan share some common regulatory pathways, which suggests a new approach for studying aging and longevity on the basis of the regulation of cellular reprogramming."

Link: http://www.ncbi.nlm.nih.gov/pubmed/21615676

I had an artistic vision, a long time back, shortly after I had my initial realization with regard to engineered longevity, of the path to radical life extension as a sort of vertical ascension. I recall describing the vision of flight through darkness years ago, to my partner at the time - the rest of that conversation lost, along with much else, to failing memory. A room is packed with thousands of people, waiting. The walls and ceiling then unfold to reveal a void beyond, and the assembled masses begin to ascend towards some distant goal - arms spread and looking up in anticipation, as they fly upward, empowered by their own sheer force of will. The energies of their passage glow blue in the darkness, a thousand, thousand trails of light. But with each moment, some falter, and fall away into the abyss, their light-trails vanishing into the surrounding darkness - and the crowd thins and thins the further they ascend.

I am not an artist, needless to say, and so that vision will never make it much beyond the confines of my head. But it is an ugly reality of the human condition that only a fraction of us will have the opportunity to live through into the age of rejuvenation biotechnology - even under the most optimistic timelines, billions will die. The alternatives are far worse, of course, but this is far from the best of worlds. Intellectually we can grasp this scale of death and destruction, but the ape within filters it out. He only cares about the people we associate with - and there aren't all that many of them, even allowing for the artificial and strange relationships of celebrity or much-loved fiction. The rest of the world? Just numbers.

That memory of people in flight through darkness is with me again because I learned today that my former partner died a few weeks ago, unexpectedly. As though the expectedness or the delay in learning of it should change anything of the meaning, but the ape within feels - strongly - that the details of tragedy are important. If we felt even a minuscule fraction of what we do under such circumstances for the vast crowds who fall from the flight each and every day, aged to death ... well, we'd be better than human, and aging would be much further along the path to a solution.

More than a hundred people have died since I started to write this post, most of them from aging or the complications of aging. All just as much individuals as my former partner, just as much people with attachments, potential, things to do, desires and regrets. So very many regrets. But I feel only intellectual loss for that hundred, and not much of it at that - this is what it is to be built on top of a foundation of ape prehistory, to be able to put the terrible fates of countless others easily from our minds, but to be deeply troubled by the loss of one.

To make the best of being human, we have to do the important work, even though it will not reward us, even though the ape inside doesn't really give a damn. Being human is about not letting the ape drive, even though it's always far easier just to let him take the wheel. So no obituary and no talking to the dead to say things that perhaps should have been said one day - and now can't be. Hard as it may be. The only person who would be listening here is the ape inside, and talking to him is a pointless exercise.

The world, meanwhile, is lived in by the living - who are falling from the flight in great numbers, day after day, while too little is being done about it. When whatever happens to me eventually happens to me, I would hope that someone takes a few minutes to write exactly the same thing, and mean it.