This research illustrates one of the many challenges associated with untangling genetic contributions to longevity; some of those genes affect personality traits that are also known to correlate with longevity:

A variant of a gene associated with active personality traits in humans seems to also be involved with living a longer life. [This] derivative of a dopamine-receptor gene - called the DRD4 7R allele - appears in significantly higher rates in people more than 90 years old and is linked to lifespan increases in mouse studies.

The variant gene is part of the dopamine system, which facilitates the transmission of signals among neurons and plays a major role in the brain network responsible for attention and reward-driven learning. The DRD4 7R allele blunts dopamine signaling, which enhances individuals' reactivity to their environment.

People who carry this variant gene [seem] to be more motivated to pursue social, intellectual and physical activities. The variant is also linked to attention-deficit/hyperactivity disorder and addictive and risky behaviors. "While the genetic variant may not directly influence longevity, it is associated with personality traits that have been shown to be important for living a longer, healthier life. It's been well documented that the more you're involved with social and physical activities, the more likely you'll live longer. It could be as simple as that."

Link: http://news.uci.edu/press-releases/dopamine-receptor-gene-variant-linked-to-human-longevity/

Source:
http://www.fightaging.org/archives/2013/01/dopamine-receptor-variant-associated-with-longevity.php

I'd wager that the future of cell therapy probably won't involve much in the way of cell transplants, not even those created from the patient's own tissues. Instead it will be based on instructing existing cell populations in the body to take specific actions - progress here will proceed at a pace determined by how well researchers can catalog and understand the enormously complex networks of cell signaling that exists in every tissue type.

Even though there is a long way to go yet in creating that catalog, a range of possible therapies are already under investigation based on what is presently understood of controlling cell behavior. There is certainly no shortage of methods for changing the cell and its environment - only a shortage in knowing which of the million levers to pull and dials to set in order to achieve the desired result with minimal side-effects. Consider that a cell is a collection of machines built out of proteins, and the controlling mechanisms are driven by the presence and levels of yet more proteins: any technique that manipulates the level of a certain protein can be used to potentially good effect. So there is plain old gene therapy to make cells produce more of a protein encoded by a specific gene. There is RNA interference to block a specific protein. There are all sorts of other ways to tinker with how much of a specific protein is produced from the blueprint of a specific gene at a given time: gene expression is a process of many intricate stages, and the research community can presently accurately target most of them, provided the time is put in.

So all this said, we see technology demonstrations like the one noted below: no transplants, just instructing cells to do something different.

Gene therapy reprograms scar tissue in damaged hearts into healthy heart muscle

A cocktail of three specific genes can reprogram cells in the scars caused by heart attacks into functioning muscle cells, and the addition of a gene that stimulates the growth of blood vessels enhances that effect. "The idea of reprogramming scar tissue in the heart into functioning heart muscle was exciting. The theory is that if you have a big heart attack, your doctor can just inject these three genes into the scar tissue during surgery and change it back into heart muscle."

During a heart attack, blood supply is cut off to the heart, resulting in the death of heart muscle. The damage leaves behind a scar and a much weakened heart. Eventually, most people who have had serious heart attacks will develop heart failure.

Changing the scar into heart muscle would strengthen the heart. To accomplish this, during surgery, [researchers] transferred three forms of the vascular endothelial growth factor (VEGF) gene that enhances blood vessel growth or an inactive material (both attached to a gene vector) into the hearts of rats. Three weeks later, the rats received either Gata4, Mef 2c and Tbx5 (the cocktail of transcription factor genes called GMT) or an inactive material.

The GMT genes alone reduced the amount of scar tissue by half compared to animals that did not receive the genes, and there were more heart muscle cells in the animals that were treated with GMT. The hearts of animals that received GMT alone also worked better as defined by ejection fraction than those who had not received genes. [The] hearts of the animals that had received both the GMT and the VEGF gene transfers had an ejection fraction four times greater than that of the animals that had received only the GMT transfer.

There will be a lot more of this sort of thing going on in the years ahead.

Source:
http://www.fightaging.org/archives/2013/01/instructing-scar-tissue-to-change-itself-into-healthy-tissue.php

A new candidate for building an Alzheimer's therapy shows promise in mice:

When a molecule called TFP5 is injected into mice with disease that is the equivalent of human Alzheimer's, symptoms are reversed and memory is restored - without obvious toxic side effects. "We hope that clinical trial studies in AD patients should yield an extended and a better quality of life as observed in mice upon TFP5 treatment. Therefore, we suggest that TFP5 should be an effective therapeutic compound."

To make this discovery, [researchers] used mice with a disease considered the equivalent of Alzheimer's. One set of these mice were injected with the small molecule TFP5, while the other was injected with saline as placebo. The mice, after a series of intraperitoneal injections of TFP5, displayed a substantial reduction in the various disease symptoms along with restoration of memory loss. In addition, the mice receiving TFP5 injections experienced no weight loss, neurological stress (anxiety) or signs of toxicity. The disease in the placebo mice, however, progressed normally as expected. TFP5 was derived from the regulator of a key brain enzyme, called Cdk5. The over activation of Cdk5 is implicated in the formation of plaques and tangles, the major hallmark of Alzheimer's disease.

Link: http://www.eurekalert.org/pub_releases/2013-01/foas-pcr010213.php

Source:
http://www.fightaging.org/archives/2013/01/tfp5-shows-promise-for-treating-alzheimers-disease.php

One of the many things that can be accomplished today, but largely isn't due to regulation, is infusion of a large number of immune cells grown from a patient's own cells. Existing immune cells - or even skin cells - can be reprogrammed to form induced pluripotent stem cells, which can then be then expanded in number and redifferentiated into the hunter killer cells that rove the body in search of things to destroy.

So why not look ahead to a range of treatments that involve temporarily endowing a person with twice as many immune cells as he or she normally possesses? Or five times as many, or ten times as many, or more? There may well be a why not, at least one that lies beyond the concern shared with all stem cell treatments, which is controlling these cells well enough to avoid the risk of pluripotent cells slipping through and generating some form of cancer. That why not hasn't surfaced yet, however, and the fastest way to see whether or not it exists is more research, more clinical trials, and more responsible medical tourism.

The potential benefits are enormous, and much of the caution forced upon research and development in the US and Europe is both unnecessary and in place for reasons that have little to do with ensuring good outcomes.

In any case, researchers here demonstrate some of the basic methodologies needed to give someone a temporarily superhuman immune system:

Stem Cell Technology Could Help Harness Patients' Own Immune Cells to Fight Disease

The techniques the groups employed involved using known factors to revert mature immune T cells into induced pluripotent stem cells (iPSCs), which can differentiate into virtually any of the body's different cell types. The researchers then expanded these iPSCs and later coaxed them to redifferentiate back into T cells. Importantly, the newly made T cells were "rejuvenated" with increased growth potential and lifespan, while retaining their original ability to target cancer and HIV-infected cells. These findings suggest that manipulating T cells using iPSC techniques could be useful for future development of more effective immune therapies.

In one study, investigators used T cells from an HIV-infected patient. The redifferentiated cells they generated had an unlimited lifespan and contained long telomeres, or caps, on the ends of their chromosomes, which protect cells from aging. This is significant because normal aging of T cells limits their expansion, making them inefficient as therapies. "The system we established provides 'young and active' T cells for adoptive immunotherapy against viral infection or cancers."

It is worth noting that this isn't the first time researchers have shown that reprogramming cells to become pluripotent and then recreating their original lineage from those pluripotent cells has the effect of rejuvenating aspects of their biology. You might recall that researchers demonstrated mitochondrial rejuvenation via this methodology a few years back.

Source:
http://www.fightaging.org/archives/2013/01/why-not-infuse-a-person-with-many-many-many-immune-cells.php

Stephen Valentine is the architect on the ofttimes seemingly dormant Timeship project, which drifted back into the news recently. It was suggested at the time that the goal is less to build something for the cryonics industry and more to provide a tax shelter for those who seek to take advantage of cryonics, which might explain some otherwise puzzling aspects of the initiative. Cryonic providers are not at the vanguard of a wealthy industry by any means, and the Timeship seems out of place in in scale and goals when compared to the ongoing, practical work of small foundations and businesses in this narrow marketplace.

In any case, here's an article that includes thoughts from Valentine:

No one's claiming that human reanimation is within our grasp yet, although the Cryonics Institute claims that insects, vinegar eels and human brain tissue (not to mention human embryos, as shown by the growing success of IVF treatment) have been stored at liquid nitrogen temperature, at which point all decay ceases, and then revived fully.

"No one's saying, 'Hey, we cryopreserved a dog and brought it back,'" says Stephen. "The breakthroughs come at a slow, slow pace, but the advantage with being cryopreserved is that you have time. If they can work it out in 100 or 200 years, you're not going anywhere. You're on ice for a while..."

The early part of the procedure is now certainly feasible, thanks to a process called vitrification. Before, one of the main stumbling blocks to freezing bodies was the damage caused to tissue by ice crystals (think about how inferior a steak that's been in the freezer tastes: that's because of molecular damage caused by crystallisation).

Not surprisingly, Stephen is optimistic. "Many scientists are saying that this is going to be considered the century of immortality," he says. [Meanwhile], he insists that life-preservation is not just for the elite few. "This is no exclusive club," he says. "It's affordable to anybody, because it can be paid for through life insurance. Most people around the world can do it if they want."

Irritated that doubters still see life extension as a crackpot notion, Stephen points out that every major scientific breakthrough in history was once deemed unthinkable. "When Christiaan Barnard did the first heart transplant in 1967 in South Africa, they thought the guy was an unethical monster," he says. "Today, thousands of heart transplants take place every year and - rightly - no one questions the moral or ethical issues of it."

The international cryonics community certainly has no shortage of widely celebrated scientists on its side. Marvin Minsky, the pioneer of artificial intelligence, is a supporter; Ray Kurzweil, the author and inventor, has signed up with for preservation with Alcor; molecular nanotechnologist K Eric Drexler is an advocate; as are prominent stem-cell researcher Michael West and Aubrey de Grey, a prominent gerontologist (the scientific study of ageing).

Source:
http://www.fightaging.org/archives/2012/12/an-interview-with-stephen-valentine.php

Looking back at past commercial development in medicine is a fair way to manage expectations for present efforts to bring therapies to the clinic. The short version of the story is that there are certainly cycles in which expectations outpace results, but those results arrive in the end:

Like many advanced technologies, the field of regenerative medicine has gone from boom to nearly bust to boom again in the span of just 30 years. Today, there are over 55 regenerative medicine products on the market focused on diverse therapeutic areas, including repair of skin/soft tissue, wound care, cardiology, oncology, and diabetes. Thirty years in, regenerative medicine has truly "come of age," the result of a tenacious pursuit to translate groundbreaking research into therapeutic products and overcome initial setbacks that almost derailed this critical new medical approach.

Yet while the past decade's focus on scientific advances and business fundamentals has propelled regenerative medicine forward, I believe this is just the start. By reflecting on the successes and lessons learned over the past three decades, we can begin to chart a roadmap for the future that will help to ensure that regenerative medicine continues to deliver important new treatments for patients, while creating sustainable value for shareholders.

From its origins in the mid-1980s, regenerative medicine was greeted with the kind of extreme excitement that has accompanied other potential breakthroughs, including monoclonal antibodies and RNA interference. By the year 2000, more than a decade after the first companies were formed, regenerative medicine companies were valued at over $2.6 billion, TIME named tissue engineering one of the hottest jobs for the 21st century, and Barron's predicted it would become a $100 billion industry. A few years later, the bubble had burst, and company valuations plummeted to a tenth of their year 2000-high.

Several factors contributed to these setbacks. First, like many new medical advances, expectations far exceeded reality. Investors and the media saw incredible promise in early research, and unrealistic timelines were set for when a product could be on the market. Second, the initial regenerative medicine products to reach the market had limited commercial success, as the few companies in the space had not yet understood all that was required to achieve both clinical and commercial success. From a scientific perspective, the field was poised to deliver, but it had not yet developed the regulatory, business, and commercial expertise required for long-term success.

In the wake of these setbacks, there came a clear understanding of what was needed to propel regenerative medicine forward and strike the appropriate balance between promise and reality. When I joined Organogenesis in 2003, the company was emerging from bankruptcy and a dissolved commercial partnership with big pharma. In the decade since, I have experienced firsthand the rebirth of our company, and on a larger scale, of the regenerative medicine field itself. Our path over the past decade has taught us several lessons about what it will take to succeed in this space going forward.

Link: http://www.genengnews.com/gen-articles/regenerative-medicine-engineering-its-continued-success/4653/

Source:
http://www.fightaging.org/archives/2012/12/considering-the-business-of-regenerative-medicine.php

Here is a review paper that looks back at the recent history of biogerontology as a field of study, noting the struggle with long-held perceptions of fraud associated with the intersection of aging and medicine:

Through archival analysis this article traces the emergence, maintenance, and enhancement of biogerontology as a scientific discipline in the United States. At first, biogerontologists' attempts to control human aging were regarded as a questionable pursuit due to: perceptions that their efforts were associated with the long history of charlatanic, anti-aging medical practices; the idea that anti-aging is a "forbidden science" ethically and scientifically; and the perception that the field was scientifically bereft of rigor and scientific innovation.

The hard-fought establishment of the National Institute on Aging, scientific advancements in genetics and biotechnology, and consistent "boundary work" by scientists, have allowed biogerontology to flourish and gain substantial legitimacy with other scientists and funding agencies, and in the public imagination. In particular, research on genetics and aging has enhanced the stature and promise of the discipline by setting it on a research trajectory in which explanations of the aging process, rather than mere descriptions, have become a central focus. Moreover, if biogerontologists' efforts to control the processes of human aging are successful, this trajectory has profound implications for how we conceive of aging, and for the future of many of our social institutions.

Link: http://www.ncbi.nlm.nih.gov/pubmed/23264719

Source:
http://www.fightaging.org/archives/2012/12/the-emergence-of-biogerontology-as-a-discipline.php

The Eurosymposium on Healthy Aging took place in Brussels earlier this month, a gathering of researchers and advocates for longevity science. The presentations were recorded and videos have been posted to Youtube. I encourage you to browse. Here is a report on the event:

Theoretical questions of longevity were covered in the first day, including such themes as the general overviews of ageing theories, molecular damage in ageing, mitochondria and autophagy. The general panel on causes, mechanisms, and interventions in aging, featured Drs. Aubrey de Grey, David Gems, Kris Verburgh, and Diana Van Heemst, and was moderated by Sven Bulterijs of HEALES.

The second day featured an inspiring plethora of promising potential interventions for increasing healthy longevity: genetics of aging and centenarians research, nutritional and pharmacological interventions in aging, biomedical interventions such as repair of damaged mitochondria, destruction of senescent cells, use of telomerase to extend health span, remediation of the Alzheimer's disease, and regenerative medicine, including both cell material and computational aspects.

The main subject of the third day was the political and social promotion of research into the biology of aging and healthy longevity. Discussion groups were formed and tentative suggestions made for increasing funding for life extension research, improving public opinion of life extension, and scientific positioning of life-extension.

Link: http://hplusmagazine.com/2012/12/19/the-brussels-summit-of-longevity-activists/

Source:
http://www.fightaging.org/archives/2012/12/a-report-from-the-eurosymposium-on-healthy-aging.php

Perhaps I'm just paying greater attention to the topic of late, but it seems like a fair number of large statistical studies that correlate exercise with increased life expectancy have shown up in the past couple of years - more than I recall prior to that. A few examples from the archives:

• Exercise, Longevity, and Long Term Medical Costs
• The Power of Moderate Exercise
• Another Study Suggests that Sedentary Behavior Adds Up

Here is a newly published study on this topic that pulls from a data set of around 95,000 people. It is presently open access, which is not usually the case for the journal in question, so take advantage of it while it lasts:

Years of Life Gained Due to Leisure-Time Physical Activity in the U.S.

Data from the National Health and Nutrition Examination Survey (2007-2010); National Health Interview Study mortality linkage (1990-2006); and U.S. Life Tables (2006) were used to estimate and compare life expectancy at each age of adult life for inactive (no moderate to vigorous physical activity); somewhat-active (some moderate to vigorous activity); and active ([more] moderate to vigorous activity) adults. Analyses were conducted in 2012.

Somewhat-active and active non-Hispanic white men had a life expectancy at age 20 years that was ?2.4 years longer than that for the inactive men; this life expectancy advantage was 1.2 years at age 80 years. Similar observations were made in non-Hispanic white women, with a higher life expectancy within the active category of 3.0 years at age 20 years and 1.6 years at age 80 years. In non-Hispanic black women, as many as 5.5 potential years of life were gained due to physical activity. Significant increases in longevity were also observed within somewhat-active and active non-Hispanic black men; however, among Hispanics the years-of-life-gained estimates were not significantly different from 0 years gained.

The estimates in the present study for non-Hispanic white men aged 20 years [suggest] that 2.6 hours [of overall life expectancy] are gained per hour of moderate activity and 5.2 hours were gained per hour of vigorous activity accrued in adulthood.

The effects of exercise on general health over the long term are possibly more striking. You can't exercise your way out of aging, but you can laze your way into a much more unpleasant and expensive later life. Exercise, calorie restriction, and the like are small stopgap measures, the poor and miserable best we can do right now in order to gain a better chance of being alive and in good health to great the arrival of rejuvenation biotechnologies - therapies that will repair and reverse the cellular and molecular damage that drives aging.

We need those biotechnologies to get out of this hole alive. They are the most important goal - don't lose sight of that behind the constant deluge of data on health, life expectancy, and how we can presently modestly adjust the pace at which we're aging to death.

Source:
http://www.fightaging.org/archives/2012/12/years-of-life-gained-due-to-leisure-time-physical-activity.php

Mitochondria are the power plants of your cells, responsible for creating the energy stores that are used to power cellular operations. Mitochondrial composition is an important determinant of longevity, and accumulating mitochondrial damage - self-inflicted in the course of the operation of metabolism - is one of the root causes of aging. Here researchers review what is know of mitochondrial decline in aging, and the ways in which mitochondrial function can be altered to extend life in laboratory animals:

For decades, aging was considered the inevitable result of the accumulation of damaged macromolecules due to environmental factors and intrinsic processes. Our current knowledge clearly supports that aging is a complex biological process influenced by multiple evolutionary conserved molecular pathways. With the advanced age, loss of cellular homeostasis severely affects the structure and function of various tissues, especially those highly sensitive to stressful conditions like the central nervous system.

In this regard, the age-related regression of neural circuits and the consequent poor neuronal plasticity have been associated with metabolic dysfunctions, in which the decline of mitochondrial activity significantly contributes. Interestingly, while mitochondrial lesions promote the onset of degenerative disorders, mild mitochondrial manipulations delay some of the age-related phenotypes and, more importantly, increase the lifespan of organisms ranging from invertebrates to mammals.

Here, we survey the insulin/IGF-1 and the TOR signaling pathways and review how these two important longevity determinants regulate mitochondrial activity. Furthermore, we discuss the contribution of slight mitochondrial dysfunction in the engagement of pro-longevity processes and the opposite role of strong mitochondrial dysfunction in neurodegeneration.

http://www.frontiersin.org/Genetics_of_Aging/10.3389/fgene.2012.00244/full

Source:
http://www.fightaging.org/archives/2012/12/reviewing-mitochondrial-activity-and-longevity.php

I noticed a good, comprehensible open access paper today: a review that summarizes what is known of the biology of the most common type of long-lived genetically engineered mouse species, those with disrupted or suppressed growth hormone (GH) activity. These include Ames dwarf mice, Snell dwarf mice, and growth hormone receptor knockout (GHRKO) mice. The present record for mouse longevity is held by the results of a GHRKO study, some of the mice involved living more than 60% longer than peers.

If you'd like to better understand how this all fits together under the hood and how it relates to other areas of study where metabolism, genetic engineering, and aging overlap - such as calorie restriction - then take a look:

Metabolic characteristics of long-lived mice

The remarkable extension of longevity in mice lacking GH or GH receptors appears to be due to multiple interacting mechanisms including reduced activation of growth-promoting pathways, greater stress resistance, reduced inflammation, increased reservoir of pluripotent stem cells, and improved genome maintenance.

Data summarized in this article indicate that alterations in energy metabolism and improved insulin control of carbohydrate homeostasis have to be added to this list. In fact, these metabolic adaptations may represent key features of the "longevous" phenotype of these animals and important mechanisms of the extension of both healthspan and lifespan in GH-related mutants.

Importantly, many of the metabolic features of long-lived mutant mice described in this article have been associated with extended human longevity. Comparisons between centenarians and elderly individuals from the same population and between the offspring of exceptionally long-lived people and their partners indicate that reduced insulin, improved insulin sensitivity, increased adiponectin, and reduced pro-inflammatory markers consistently correlate with improved life expectancy.

Source:
http://www.fightaging.org/archives/2012/12/an-introduction-to-whats-going-on-inside-long-lived-mice.php

A successful demonstration of a novel form of immune therapy is noted in this article, and described in a recently published paper:

An experimental "Trojan-horse" cancer therapy has completely eliminated prostate cancer in experiments on mice. [The] team hid cancer killing viruses inside the immune system in order to sneak them into a tumour. [After] chemotherapy or radiotherapy is used to treat cancer, there is damage to the tissue. This causes a surge in white blood cells, which swamp the area to help repair the damage. "We're surfing that wave to get as many white blood cells to deliver tumour-busting viruses into the heart of a tumour."

[Researchers] blood samples and extract macrophages, a part of the immune system which normally attacks foreign invaders. These are mixed with a virus which, just like HIV, avoids being attacked and instead becomes a passenger in the white blood cell. In the study, the mice were injected with the white blood cells two days after a course of chemotherapy ended. At this stage each white blood cell contained just a couple of viruses. However, once the macrophages enter the tumour the virus can replicate. After about 12 hours the white blood cells burst and eject up to 10,000 viruses each - which go on to infect, and kill, the cancerous cells.

At the end of the 40-day study, all the mice who were given the Trojan treatment were still alive and had no signs of tumours. By comparison, mice given other treatments died and their cancer had spread.

Link: http://www.bbc.co.uk/news/health-20795977

Source:
http://www.fightaging.org/archives/2012/12/using-immune-cells-to-deliver-cancer-killing-viruses.php

The modern age of antibiotics didn't do a great deal to combat the inexorable processes that contribute to tooth decay and gum disease, as it things turned out. One might have thought so at the outset: bacteria in the mouth are causing issues, we're developing all sorts of enormously improved methods of killing bacteria, ergo tooth decay and commonplace gum disease like gingivitis and should soon be a thing of the past. Alas not so, however - nothing is straightforward in the world of medicine. As one consideration, many of the hundreds of bacterial species in the mouth are actually beneficial.

In recent years, there has been some progress towards more sophisticated solutions. These include methods of sabotaging key mechanisms in problem bacterial species so as to leave other bacteria unharmed, or of targeting bacteria by their surface chemistry or other markers. For example:

• The End of Tooth Decay Looms Large
• The Possibility of Eliminating Tooth Decay
• Progress Towards Cavity Vaccines

I noticed another line of work in this field; here researchers are sabotaging the progression of gum inflammation caused by bacteria:

Penn-Led Research Suggests a New Strategy to Prevent or Halt Periodontal Disease

Porphyromonas gingivalis, the bacterium responsible for many cases of periodontitis, acts to "hijack" a receptor on white blood cells called C5aR. The receptor is part of the complement system, a component of the immune system that helps clear infection but can trigger damaging inflammation if improperly controlled. By hijacking C5aR, P. gingivalis subverts the complement system and handicaps immune cells, rendering them less able to clear infection from the gum tissue. As a result, numbers of P. gingivalis and other microbes rise and create severe inflammation. According to a study published [last year], mice bred to lack C5aR did not develop periodontitis.

[The] researchers synthesized and administered a molecule that blocks the activity of C5aR, to see if it could prevent periodontitis from developing. They gave this receptor "antagonist," known as C5aRA, to mice that were then infected with P. gingivalis. The C5aRA injections were able to stave off inflammation to a large extent, reducing inflammatory molecules by 80 percent compared to a control, and completely stopping bone loss. And when the mice were given the antagonist two weeks after being infected with P. gingivalis, the treatment was still effective, reducing signs of inflammation by 70 percent and inhibiting nearly 70 percent of periodontal bone loss.

I suspect that the next generation will very rarely visit dentists, as much of the need for regular dental services will be removed by products based on this and similar sorts of research.

Source:
http://www.fightaging.org/archives/2012/12/at-some-point-soon-mouth-bacteria-will-be-defeated.php

It should be noted that, on balance, everything except physical health becomes better with age. Outside of degenerative aging, becoming older is so good that people are driven to apologism for the fact that aging cripples and kills them - they conflate being old and being aged, seeing two very different things as one, and a certain confusion arises after that point.

Consider how much better it will be to be older once we start being able to treat the root causes of the degenerative medical condition called aging. If you're not there yet, consider just how good being older must be in order for people to be able to say they are well off even while their health is crumbling:

The SAGE study included adults between the ages of 50 and 99 years, with a mean age of just over 77 years. In addition to measures which assessed rates of chronic disease and disability, the survey looked at more subjective criteria such as social engagement and participants' self-assessment of their overall health.

Participants were asked to rate the extent to which they thought they had "successfully aged," using a 10-point scale and using their own concept of the term. The study found that people with low physical functioning but high resilience, had self-ratings of successful aging similar to those of physical healthy people with low resilience. Likewise, the self-ratings of individuals with low physical functioning but no or minimal depression had scores comparable to those of physically healthy people with moderate to severe depression.

"It was clear to us that, even in the midst of physical or cognitive decline, individuals in our study reported feeling that their well-being had improved with age."

Link: http://www.eurekalert.org/pub_releases/2012-12/uoc--poa120312.php

Source:
http://www.fightaging.org/archives/2012/12/being-older-is-very-positive-being-aged-is-not.php

Researchers have found a number of potential ways to spur growth of muscle tissue, and some of these might be used in attempts to fend off the loss of muscle mass and strength that occurs with aging - not by fixing the root causes, but by trying to compensate through another mechanism. Here is a recent example:

The protein is an isoform, or slight variant, of PGC-1 alpha, an important regulatory of body metabolism that is turned on by forms of exercise, such as running, that increase muscular endurance rather than size. [A rise in] PGC-1 alpha-4 with exercise increases activity of a protein called IGF1 (insulin-like growth factor 1), which facilitates muscle growth. At the same time, PGC-1 alpha-4 also represses another protein, myostatin, which normally restricts muscle growth. In effect, PGC-1 alpha-4 presses the accelerator and removes the brake to enable exercised muscles to gain mass and strength.

Several experiments demonstrated the muscle-enhancing effects of the novel protein. The investigators used virus carriers to insert PGC-1 alpha-4 into the leg muscle of mice and found that within several days their muscle fibers were 60 percent bigger compared to untreated mice. They also engineered mice to have more PGC-1 alpha-4 in their muscles than normal mice who were not exercising. Tests showed that the treated mice were 20 percent stronger and more resistant to fatigue than the controls; in addition, they were leaner than their normal counterparts.

Link: http://www.sciencedaily.com/releases/2012/12/121206121728.htm

Source:
http://www.fightaging.org/archives/2012/12/pgc-1-alpha-4-spurs-muscle-growth.php

Many of the early forms of stem cell therapy involve cell transplants, and seem to produce benefits without those transplanted cells creating replacements for lost native cells. Instead the newcomers are improving the local environment and issuing signals that allow greater survival and repair among the native cell populations. Here is an example of the type:

Promising new research provides evidence that amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease, may be treatable using neural stem cells. A consortium of researchers at multiple institutions [have] shown that neural stem cells, when transplanted into the spinal cord of a mouse model with familial ALS, slow disease onset and progression while improving motor function, breathing and survival time compared to untreated mice.

Neural stem cells are the precursors of all brain cells. They can self-renew, making more neural stem cells, and differentiate, becoming nerve cells or other brain cells. These cells can also rescue malfunctioning nerve cells and help preserve and regenerate brain tissue. But they've never before been studied extensively in a good model of adult ALS.

In 11 independent studies [researchers] transplanted neural stem cells into the spinal cord of a mouse model of ALS. The transplanted neural stem cells benefited the mice with ALS by preserving the health and function of the remaining nerve cells. Specifically, the neural stem cells promoted the production of protective molecules that spared remaining nerve cells from destruction. They also reduced inflammation and suppressed the number of toxin-producing and disease-causing cells in the host's spinal cord.

Link: http://www.eurekalert.org/pub_releases/2012-12/uomm-tns121912.php

Source:
http://www.fightaging.org/archives/2012/12/treating-als-with-neural-stem-cell-transplants.php

Retinal implants are currently in their earliest stage of development: comparatively crude electrode arrays that provide an alternative to vision rather than restoring it. From here the path to ever more sophisticated systems seems assured, however:

A coming generation of retinal implants that fit entirely inside the eye will use nanoscale electronic components to dramatically improve vision quality for the wearer, according to two research teams developing such devices.

Current retinal prostheses, such as Second Sight's Argus II, restore only limited and fuzzy vision to individuals blinded by degenerative eye disease. Wearers can typically distinguish light from dark and make out shapes and outlines of objects, but not much more. The Argus II, the first "bionic eye" to reach commercial markets, contains an array of 60 electrodes, akin to 60 pixels, that are implanted behind the retina to stimulate the remaining healthy cells. The implant is connected to a camera, worn on the side of the head, that relays a video feed.

A similar implant, made by Bionic Vision Australia, incorporates just 24 electrodes. With so few electrodes, the amount of visual information transmitted to the brain is limited: text, for example, is difficult to read. Second Sight recently announced a method by which Argus II wearers are able to visualize Braille instead of traditional text.

Recognizing this limitation, both Second Sight and Bionic Vision Australia have announced that they are developing next-generation devices with 200-plus electrodes. But arrays of nanoscale electrodes, which are currently being incorporated into new retina devices, could someday give blind people 20/20 vision.

Link: http://www.technologyreview.com/news/508041/vision-restoring-implants-that-fit-inside-the-eye/

Source:
http://www.fightaging.org/archives/2012/12/a-brief-look-at-retinal-implants.php

The latest supplement from Nature contains a collection of articles on the topic of aging, largely from the mainstream research community viewpoint that centers on modestly slowing aging as a goal rather than anything more ambitious:

Humans are the longest lived primates, with life expectancy in some developed nations surpassing 80 years. Of course, that doesn't stop us wanting more time. Research into the mechanisms of ageing is yielding insights, many of them diet-related, into how we might not only live longer but also stay healthier as we do.

I'll point you to a couple of the more interesting pieces, which review some of the knowledge gained in recent years:

Comparative biology: Looking for a master switch

Comparative studies are beginning to give clues to the cellular and molecular mechanisms that enable some species to live longer than related species. Miller's team, for example, cultured skin cells from nine rodent species and exposed them to various stresses, including cadmium, hydrogen peroxide and heat. Similar experiments involved skin cells from 35 different bird species. Both studies showed that cells from long-lived animals are more resistant to stresses than those of short-lived species, says Miller.

Similar research also suggests one possible reason why birds tend to live longer than mammals of similar size, Miller adds. "Bird cells tend to be three- to ten-fold more resistant to many of these stresses than cells from rodents of the same size. We can't prove that's why birds live a long time, but it's a good guess."

Interventions: Live long and prosper

While researchers wait for statistical proof of the diet's effects in primates, some people have elected to go on the diet anyway. CRONies - the label adopted by those on a diet of Caloric Restriction with Optimal Nutrition - voluntarily eat 30% fewer calories than recommended by the US Department of Agriculture. That can be as low as 1,400 calories a day for men, and 1,120 for women.

Fontana, who studies the CRONies, says most of the health benefits seen in animals on the caloric restriction diet also appear in humans. He says that people who started caloric restriction in middle age and stayed with the regimen for eight years have a "fantastic" cardiometabolic profile. He adds that he has seen subjects in their late 70s with the blood pressure of teenagers.

Stem cells: Repeat to fade

As with so much else, stem cells in an older person are not the same as those in someone younger. They tend to be less productive and less reliable, and become slower and less predictable when it comes to replenishing cells affected by injury, illness or senescence - and the tissues they serve become less healthy and vital. In other words, stem cells are prominent in the fundamental biology of ageing. If stem cells in older people could be made to retain their effectiveness, perhaps broken bones and skin wounds could be made to heal faster and, with time, we might be able to treat the conditions of old age, such as dementia and heart disease.

Source:
http://www.fightaging.org/archives/2012/12/nature-outlook-ageing.php

Over the years a great many studies have been conducted using laboratory animals with the aim of recording changes in life span that result from drugs, genetic alterations, and environmental conditions. The shorter-lived and less costly to maintain the species, the more studies there are - probably thousands for nematode worms, for example.

If you feel like browsing through the stacks to gain an impression of the work that has taken place over the past few decades, allow me to point you to the Lifespan Observations Database, which "collects published lifespan data across multiple species." It isn't a complete reference, but contains thousands of entries. Here are counts by species:

• C. elegans: 3315
• S. cerevisiae: 1046
• D. melanogaster: 298
• M. musculus: 175
• P. anserina: 22
• R. norvegicus: 15
• S. pombe: 12
• C. albicans: 6
• N. furzeri: 6
• E. coli: 4
• C. remanei: 2
• M. auratus: 2
• L. longipalpis: 2
• H. sapiens: 2
• E. postfasciatus: 2
• D. pseudoobscura: 1
• C. capitata: 1

Browsing the entries shows change in life span and other items of interest. For example, picking one at random for mice:

Species: Mus musculus

Strain: 129 SvEv

Lifespan: 815 days

Reference Lifespan: 761 days

Lifespan Change: 7.1%

Lifespan Measure: median

Lifespan Effect: increased

Significance: significant

Citation: Migliaccio E, Giorgio M, Mele S, Pelicci G, Reboldi P, Pandolfi PP, Lanfrancone L, Pelicci PG. (1999). The p66shc adaptor protein controls oxidative stress response and life span in mammals.. Nature 402: 309-13. [pubmed]

Details: Mice mutant for p66shc have increased life span of 30%. Homozygous mutants are longer-lived than heterozygotes.

Other phenotypes: p66shc -/- cells are more resistant to apoptosis induced by hydrogen peroxide and UV light. p66shc -/- mice are more resistant to oxidative stress induced by paraquat,

You might compare this with some of the other online databases that have been mentioned here in the past, and are interesting to look through:

• The AnAge Database
• A Comparative Cellular and Molecular Biology of Longevity Database
• A Database of Genes Related to Calorie Restriction

Source:
http://www.fightaging.org/archives/2012/11/the-lifespan-observations-database.php

You might recall past studies of elite atheletes that showed a sizable correlation with increased life expectancy:

• Atheletes Live Longer, Probably the Exercise
• Putting Upper Bounds on Longevity Derived From Exercise

Exercise and physical fitness are obviously things to point to here. Causation is harder to pin down in human studies: for example, we might ask to what degree competitive athletes are drawn their line of work because they are more robust than the average individual - and thus capable of living longer anyway. While it's certainly the case that a mountain of studies show causation for health benefits deriving from moderate exercise, there isn't as much to point to when it comes to the same for human life expectancy. There is certainly a lot of correlation in published research, however.

There are any number of other significant factors at play here when you look at statistical differences of a few years up or down in human life expectancy. For example, wealth: successful professional athletes are wealthier than the average fellow. To what degree is their longer life expectancy the result of the broad array of benefits that come with being wealthier? Easier access to medicine; more personal connections where it matters; greater likelihood of education or other access to knowledge that helps with taking advantage of medicine; and so forth.

Here is another study that shows a longevity advantage for athletes, but which unfortunately doesn't help much with questions of causation:

Olympic medalists stay alive longer, study finds

Athletes who win at the Olympics may bring home more than just a medal: They could add a few years to their life spans, scientists have found. Winners of a gold (or silver or bronze) medal lived almost three years longer on average than their country's general population - when matched for age, gender and birth year - according to a study [that] examined some 15,174 Olympic medalists.

"Some elite sportspeople may be influenced by fame and glory, which could confer longevity through increased affluence," said an editorial accompanying the research, "unless undermined by excessive partying and hazardous risk-taking behaviors."

Alternatively, survival edges could simply be due to more healthful lifestyles and physical fitness. [Researchers] said it wasn't possible to examine the longevity fates of those who competed in the Olympics but did not win a medal because records for non-winners weren't nearly as complete as those for winners.

The study is open access and very readable, so head on over and have a look at the published paper. It isn't the first to suggest that high intensity regular exercise is either no more beneficial than moderate regular exercise or no more correlated with longevity:

Our results show that former Olympic athletes who engaged in disciplines with high cardiovascular intensity had similar mortality risks to athletes from disciplines with low cardiovascular intensity. This would indicate that engaging in cycling and rowing (high cardiovascular intensity) had no added survival benefit compared with playing golf or cricket (low cardiovascular intensity).

Source:
http://www.fightaging.org/archives/2012/12/life-expectancy-in-successful-atheletes-is-a-good-example-of-why-its-hard-to-pin-down-correlations-in-human-longevity.php