If you go through the first half of your life basically healthy, there are actually only a few important differences between your situation and that of your ancestors a century or two ago when it comes to health and medical technology. For all that we live in the opening years of an era of advanced biotechnology, and in an age of far greater wealth, a healthy person benefits only through (a) the reduced burden of infectious disease, and (b) through the insulating effects of wealth against malnutrition, exposure, and other environmental misfortunes. These two points are enough to explain much of the steady rise in life expectancy that occurs with growing wealth and advancing medical technology over the past centuries.

What is the point of mentioning this? It is to remind us that we are not bathed in the golden aura of biological science, and the many ways to extend the healthy lives of mice demonstrated in the laboratory over the past decade have not yet translated into any medical technology we can use. As a healthy person in the US or Europe, the trajectory of your life under present day medicine isn't in fact terribly different from that of a privileged and healthy individual in the late 1800s. The only differences lie in your burden of infectious disease and the ability for even today's poor to enjoy a degree of protection from life's slings and arrows that was once only affordable to the wealthy. The trajectory of your life will only change meaningfully when prospective technologies for reversing the damage of aging are developed and become available in the clinic. Until then, you are only incrementally better off.

From the perspective of the life sciences and medical technology, these are amazing years to be alive, as I'm sure you've already noticed if you're a regular reader at Fight Aging! Yet that means exactly nothing for us until laboratory work is built into clinical applications. Detailed descriptions of technologies that can reverse aging give us hope, but nothing other than hope until the job of turning descriptions into real therapies is complete.

There are all too many people in the world who are happy to partake in the growing hope of engineered longevity and human rejuvenation, but who then sit back and do nothing to help bring about that desired future. And so the world works as it has always done: if everyone drinks hope and air, then hope and air is all that will come into being. Medical technologies do not develop themselves. They only arise in an environment of support, aggressive fundraising, and widespread agitation for their creation - environments in which a lot of people are materially contributing, in other words.

So don't feel as though you are made shielded or special by the fact that biotechnology is in the zeitgeist: you aren't, and you won't be until much more work is accomplished. Give some thought to helping out: after all, your life is as much on the line as everyone else's.

Here is a repetition of the sort of research from the last century that initially drew interest to calorie restriction, in which researchers are trying to pin down the point at which beneficial calorie restriction becomes harmful malnutrition: "It has been firmly established that the longevity of 20- to 60 %-calorie-restricted rodents, with malnutrition (essential nutrients deficiency) being avoided, is increased when compared to ad libitum fed rodents. However, the effects on life span of severe dietary restriction (i. e. malnutrition), with limited weight loss, remained unknown. The purpose of this 4-year study was to investigate the effects on longevity of a severe form of dietary restriction, with limited and controlled weight loss. To this end, a group of male Long-Evans rats severely dietary restricted (SDR group), with a weight loss throughout the experiment <= 25 % of their weight before the onset of the experiment at 9 weeks of age, was compared to a control group of rats 30- to 40 %-calorie-restricted (C group). Our results show that a severe dietary restriction, excessive weight loss being prevented, paradoxically increased rat longevity by nearly 50 %. The life span increase observed in our SDR rats is in accordance with some other studies investigating the effects on longevity of partial essential nutrients deficiencies (tryptophan, methionine, and fat, for example)."

Link: http://www.ncbi.nlm.nih.gov/pubmed/21792819

The recent cryosuspension of Robert Ettinger has led to a flurry of press articles; this is one of the better ones: "British photojournalist Murray Ballard, who has documented every aspect of cryonics there is to see (beyond the currently unachievable final stage, of course). Ballard's project began while he was studying photography at the University of Brighton, when he was inspired by the story of a French couple who had held hopes of being revived after their death; unfortunately the freezer storing their bodies broke down. Intrigued, the photographer's research led him first to a group of enthusiasts based just along the Sussex coast in Peacehaven, and before long he and his camera made their first trip to the three main cryonic storage sites in the US and Russia. There are around 1,000 people around the world like those in Peacehaven who have signed up to be preserved in the hope they can be reanimated in the future - with 459 having signed contracts with Ettinger's non-profit organisation - but Ballard says that most of those he has met understand it is very much an experimental and unproven science. ... During his project he paid two visits to Ettinger's institute, as well as three visits each to the KrioRus plant just outside Moscow, where another 15 'patients' are currently held in cryostasis, and the Alcor Life Extension Foundation in Arizona which holds 104. ... Essentially all you need is the brain. The theory is that the brain is like a hard drive that stores all your memories and your personality. When you are revived at some point in the distant future, a new body will be grown to house your brain, or an entirely new brain may be built for them to somehow upload your personality into it."

Link: http://www.independent.co.uk/life-style/gadgets-and-tech/features/cryonics-the-chilling-facts-2326328.html

A number of genetic modifications that enhance longevity in mice are unambiguously positive: the result is quite literally a measurably better breed of mouse, stronger, with greater endurance, or smarter, or more resilient in some other way. Downsides are minimal or non-existent. Researchers are paying more attention to benefits other than longevity that result from these studies nowadays - there are now so many ways of extending mouse life that announcing a new one won't get you much press unless it has some other novel twist to accompany it.

So here we have a novel twist: a single gene manipulation that improves mood and neural function as well as modestly extending life. Take a look at the abstract or open access PDF paper:

The role of ?1-adrenergic receptors (?1ARs) in cognition and mood is controversial, likely due to past use of non-selective agents. ?1AAR activation was recently shown to increase neurogenesis, which is linked to cognition and mood.

We studied the effects of chronic ?1AAR stimulation using transgenic mice engineered to express a constitutively active mutant (CAM). CAM-?1AAR mice showed enhancements in several behavioral models of learning and memory. ... WT mice treated with the ?1AAR-selective agonist, cirazoline, also showed enhanced cognitive functions. In addition, CAM-?1AAR mice exhibited antidepressant and less anxious phenotypes in several behavioral tests when compared to WT. Furthermore, the lifespan of CAM-?1AAR mice was 10 percent longer than that of WT mice.

Our results suggest that chronic ?1AAR stimulation improves synaptic plasticity, cognitive function, mood, and longevity. This may afford a potential therapeutic target for counteracting the decline in cognitive function and mood associated with aging and neurological disorders.

Some caution is called for however, as is the case for the results of all studies that don't control for calorie intake. Mice are so very sensitive to calorie restriction that any alteration or treatment that incidentally reduces their calorie intake will extend life - and 10 percent life extension is well within the bounds of that happenstance. If you look at the Wikipedia entry for cirazoline, you'll see:

Cirazoline has also been shown to decrease food intake in rats, purportedly through activation of alpha 1-adrenoceptors

So this is a study that should be repeated with calorie controlled mice.

Still, it remains the case that at what is still the dawn of the age of biotechnology, mice can already be tweaked in more than a score of ways to produce a better species. This raises the question of how true this is for other mammals - such as we humans, for example. Nowhere near as much work, testing, and experimentation has been performed on any other mammal species as has been accomplished with varying breeds of rodents. But we all came to have our own specific biological systems through the same general workings of evolution, and if one mammal species can be improved with a few selective genetic modifications, we might well wonder how true is that of the others:

The question for today is whether there exist as yet undiscovered and comparatively simple mutations in humans that will significantly extend healthy and maximum life spans. How likely is this, given what we know to date? Are potential human longevity mutations worth chasing?

The Technology Review looks at the work of researchers attempting to restore youthful function in brain cells associated with memory: "By delivering a certain chemical to the brain, researchers could make neurons in old monkeys behave like those in young monkeys. Clinical trials of a generic drug that mimics this effect are already underway. The findings support the idea that some of the brain changes that occur with aging are very specific - rather than being caused by a general decay throughout the brain - and can potentially be prevented. [Researchers] recorded electrical activity from neurons in a part of the brain called the prefrontal cortex, a region especially vulnerable to aging in both humans and [other] primates. It is vital for our most high-level cognitive functions, such as working memory and the ability to multitask and inhibit distractions. ... neural circuits in this region are organized to create a sustained level of activity that is crucial for working memory. ... By analyzing activity recorded from young, middle-aged, and old monkeys, the researchers found that the firing rate of the neurons in this area declines with age. They found that other neurons, such as those that respond to cues in the environment, still fired normally even as the monkeys aged. ... The researchers were able to rein in the problem by treating the cells with a drug that blocks the potassium channels. After treatment, brain cells in old monkeys fired more rapidly - just like those in their younger counterparts. The researchers already knew that giving monkeys this drug systemically, rather than delivering it directly into the brain, could reverse age-related deficits in working memory. A clinical trial of the compound, a generic drug called guanfacine, originally used to treat hypertension, is underway."

Link: http://www.technologyreview.com/biomedicine/38158/

VIa EurekAlert!: "Approximately 60 million people across the globe have chronic kidney disease, and many will need dialysis or a transplant. [Research] indicates that patients' own kidney cells can be gathered and reprogrammed. Reprogramming patients' kidney cells could mean that in the future, fewer patients with kidney disease would require complicated, expensive procedures that affect their quality of life. In the first study, [researchers] took cells from an individual's kidney and coaxed them to become progenitor cells, allowing the immature cells to form any type in the kidney. Specifically, they inserted several key reprogramming genes into the renal cells that made them capable of forming other cells. In a second study, [researchers] found that kidney cells collected from a patient's urine can also be reprogrammed in this way. Using cells from urine allows a technology easy to implement in a clinic setting. Even better, the urine cells could be frozen and later thawed before they were manipulated. If researchers can expand the reprogrammed cells - called induced pluripotent stem cells (iPSCs) - and return them to the patient, these IPSCs may restore the health and vitality of the kidneys. In addition to providing a potentially curative therapy for patients, the breakthroughs might also help investigators to study the causes of kidney disease and to screen new drugs that could be used to treat them."

Link: http://www.eurekalert.org/pub_releases/2011-07/ason-cpo072711.php

A mixed calorie restriction and intermittent fasting study focused on measuring quality of life rather than biochemical markers caught my eye today.

Efficacy of fasting calorie restriction on quality of life among aging men:

Calorie restriction (CR) has been promoted to increase longevity. Previous studies have indicated that CR can negatively affect mood and therefore the effect of CR on mood and quality of life (QOL) becomes crucial when considering the feasibility of CR in humans. We conducted a three month clinical trial on CR (reduction of 300 to 500kcal/day) combined with two days/week of Muslim sunnah fasting (FCR) to determine the effectiveness of FCR on QOL among aging men in Klang Valley, Malaysia. A total of 25 healthy Malay men (age 58.8±5.1years), with no chronic diseases and a BMI of 23.0 to 29.9kg/m(2) were randomized to FCR (n=12) and control (n=13) groups.

Body composition measurements and QOL questionnaires were ascertained at baseline, week 6 and week 12. QOL was measured using the Short-Form 36, sleep quality was determined using the Pittsburgh Sleep Quality Index, the Beck Depression Inventory II was used to measure mood and the Perceived Stress Scale was used to measure depression. The FCR group had a significant reduction in body weight, BMI, body fat percentage and depression (P<0.05). The energy component of QOL was significantly increased in FCR group (p<0.05). There were no significant changes in sleep quality and stress level between the groups as a result of the intervention. In conclusion, FCR resulted in body weight and fat loss and alleviated depression with some improvement in the QOL in our study and has the potential to be implemented on a wider scale.

One of the common knee-jerk reactions to calorie restriction as a health practice is for people to think that it will make them unhappy: less food is equated with austerity, privation, misery and so forth. Perhaps this is a part of the unintentional indoctrination we all go through in our youth as a result of fiction and history lessons - for the vast majority of human history obtaining enough food was a continual struggle. Still, to equate calorie restriction with unhappiness is a naive view, held by people in the privileged position of being so wealthy in comparison to their ancestors that they can consistently overeat to the point of harming health and shortening life over the long term.

This bottom line: what has come to pass for normal in the modern diet is in fact caloric overkill and then some, and indulging has measurable consequences in the form of poor health and higher risk of age-related and lifestyle diseases. Eating only what is optimal - considerably less that what is now normal in other words - is beneficial in comparison. It enhances some evolved responses in cellular housekeeping mechanisms, removes some of the harm done by eating too much, and generally improves matters. What's not to like?

Via ScienceDaily: "One of the latest attempts to boost the body's defenses against cancer is called adoptive cell transfer, in which patients receive a therapeutic injection of their own immune cells. This therapy, currently tested in early clinical trials for melanoma and neuroblastoma, has its limitations: Removing immune cells from a patient and growing them outside the body for future re-injection is extremely expensive and not always technically feasible. ... scientists have now tested in mice a new form of adoptive cell transfer, which overcomes these limitations while enhancing the tumor-fighting ability of the transferred cells. ... The new approach should be more readily applicable than existing adoptive cell transfer treatments because it relies on a donor pool of immune T cells that can be prepared in advance, rather than on the patient's own cells. Moreover, using a method pioneered [more] than two decades ago, these T cells are outfitted with receptors that specifically seek out and identify the tumor, thereby promoting its destruction. In the study, the scientists first suppressed the immune system of mice with a relatively mild dose of radiation. They then administered a controlled dose of the modified donor T cells. The mild suppression temporarily prevented the donor T cells from being rejected by the recipient, but it didn't prevent the cells themselves from attacking the recipient's body, particularly the tumor. This approach was precisely what rendered the therapy so effective: The delay in the rejection of the donor T cells gave these cells sufficient opportunity to destroy the tumor."

Link: http://www.sciencedaily.com/releases/2011/07/110725091728.htm

Another reason to exercise: "Senescent T-cells accumulate with age, lowering the naive T-cell repertoire and increasing host infection risk. As this response is likely to be influenced by certain lifestyle factors, we examined the association between aerobic fitness (VO(2max)) and the age-related accumulation of senescent T-cells. Blood lymphocytes from 102 healthy males (18-61yr) were analyzed for [marker] surface expression on CD4+ and CD8+ T-cells ... Advancing age (yr) was positively associated with the proportion (%) of senescent [and] CD8+ T-cells and inversely associated with naive CD4+ and CD8+ T-cells. VO(2max) was inversely associated with senescent CD4+ and CD8+. Strikingly, age was no longer associated with the proportions of senescent or naive T-cells after adjusting for VO(2max), while the association between VO(2max) and these T-cell subsets withstood adjustment for age, BMI and percentage body fat. Ranking participants by age-adjusted VO(2max) revealed that the highest tertile had had 17% more naive CD8+ T-cells and 57% and 37% less senescent CD4+ and CD8+ T-cells, respectively, compared to the lowest tertile. This is the first study to show that aerobic fitness is associated with a lower age-related accumulation of senescent T-cells, highlighting the beneficial effects of maintaining a physically active lifestyle on the aging immune system."

Link: http://www.ncbi.nlm.nih.gov/pubmed/21784146

Progress in materials science, and in the areas in which that field overlaps with biotechnology, are enabling many different lines of artificial organ development. The resulting machinery will be competitive with tissue engineering in the decades to come: everything from artificial blood through to artificial hearts and artificial kidneys are on the agenda - even artificial brain sections are under development.

Work on replacement electromechanical and bioartificial solutions for other organs are in earlier stages, and these include artificial lungs. Here, the first necessary step towards enabling lung devices as an implantable option is to make them small enough to fit into the chest cavity. Artificial lungs remain large devices in the popular imagination, but in fact have been shrinking just as rapidly as other medical technologies, as noted in a recent popular science article:

Scientists at Case Western Reserve University in Cleveland have designed an artificial lung that uses air instead of pure oxygen as a ventilating gas - an advance that could turn accompanying oxygen cylinders into relics of the past. What's more, the device for use in humans could come in at just 6x6x4 inches, which is roughly the volume of the real human lung, meaning it could conceivably pave the way for implantable artificial lungs. The team first built a miniature-feature mold, layered a liquid silicone rubber over it that hardened into artificial capillaries and alveoli, and then separated the air and blood channels with a gas diffusion membrane. By building a small unit, they were able to maximize the surface-area-to-volume ratio and shrink the distance for gas diffusion to improve efficiency.

This is a prototype technology, tested on blood but yet to be trialed over the long haul in animals. Yet it remains a good indicator of what lies ahead as researchers ever more effectively mimic or integrate biological functions in artificial devices. The mid-term future will feature a competitive race between tissue engineering and prosthetics technology, but in the long term the distinction between biological and non-biological replacement parts will begin to blur. Nanotechnology will lead to artificial cells, artificial immune systems, swarms of tiny machines to replace blood cells, and a range of other foreseeable machinery far better at their jobs than our evolved organs. It's a future worth trying to hang around for, as it will certainly include rejuvenation of one form or another: if you can make it another fifty years, there is a fair chance that you'll have the opportunity to live for centuries - or longer.