Mice lacking the gene to create the protein adenylyl cyclase 5 (AC5) live longer. This was accidentally discovered during research into potential heart therapies, and published earlier this year:

The new discovery, that knocking out a single cardiac gene could lengthen lifespan, was an unexpected byproduct of heart research. ... mutant mice lacking [the gene for protein] AC5 were more resistant to heart failure caused by pressure within the heart. But in the process, the research team also realised that the mutant mice lived longer than their normal counterparts. [Now] they report that the treated mice lived 30% longer and did not develop the heart stress and bone deterioration that often accompanies ageing.

Like many longevity mutations of this magnitude, this is thought to invoke the beneficial mechanisms of calorie restriction in some way. Researchers are still working on clarifying the action of the AC5 mutation, as illustrated by the latest paper on the topic:

Adenylyl Cyclase 5: A New Clue in the Search for the "Fountain of Youth"?

It is proposed that these beneficial effects may be the result of the increased activity of second messenger signaling proteins such as mitogen-activated or extracellular signal-regulated protein kinase kinase (MAPKK, also known as MEK) and extracellular signal-regulated kinase (ERK), or of enzymes such as manganese superoxide dismutase (MnSOD) that promote cell survival through protection against oxidative stress and apoptosis. These intriguing findings should stimulate additional research aimed at dissecting the complex cellular mechanisms regulated by AC isoforms and may lead to novel genetic and pharmacological approaches to delay aging-related conditions and to extend life span.

A fair number of bases covered there. "We don't really know yet, but have some places to start looking" would have been fine. Metabolism is complex; there's no end to the resouces we can productively sink into understanding the space of potential beneficial alterations to mammalian metabolic processes. Those same resouces, I feel, would be better directed to understanding how to repair the metabolism we have. After all, if you can repair age-related metabolic damage once, you can come back in ten years time and do it again - and again and again, for so long as you care to continue. If developing that possibility is on the table for the same sort of cost as developing a one-time manipulation that slows the accumulation of damage by 30%, I know which route I'd choose.

This is exactly the choice facing us today, and for some strange reason the mainstream of medical science is headed down the inferior, more costly, less effective path of metabolic manipulation. Comparatively little attention is given to the more effective strategies of repair. Changing this reality is one very good reason to support the work of the Methuselah Foundation.

You might recall research from last year suggesting age-related decline in the choroid plexus contributes to the buildup of amyloid characteristic to Alzheimer's disease.

the choroid plexus acts as a sort of 'fishnet' that captures the protein, called beta-amyloid, and prevents it from building up in the cerebrospinal fluid, which surrounds and bathes the brain and spinal cord. Moreover, tissue in the organ is able to soak up large amounts of the protein and may contain enzymes capable of digesting beta-amyloid.

I noticed a paper today that focuses on a quite different aspect of decline in the choroid plexus, but one that still leaves the brain the worse for it.

Aging reduces the neuroprotective capacity, VEGF secretion, and metabolic activity of rat choroid plexus epithelial cells:

Delivery of neurotrophic molecules to the brain has potential for preventing neuronal loss in neurodegenerative disorders. Choroid plexus (CP) epithelial cells secrete numerous neurotrophic factors, and encapsulated CP transplants are neuroprotective in models of stroke and Huntington's disease (HD).

...

In vitro, young CP epithelial cells secreted more VEGF and were metabolically more active than aged CP epithelial cells.

...

Implants of young CP were potently neuroprotective as rats receiving CP transplants were not significantly impaired when tested for motor function. In contrast, implants of CP from aged rats were only modestly effective and were much less potent than young CP transplants.

If (still a big if) Alzheimer's turns out to look a lot like Parkinson's at root, in that it stems from the failure of an important population of cells or narrow range of processes in the brain, the door is wide open for the next decade of regenerative therapies. There is so much we could do with the ability to grow fresh, healthy tissue to order - even in the brain.

I feel compelled to come back to a comment by Richard Sprott, director of the Ellison Medical Foundation, quoted in a recent article on investment in longevity research:

"We're all going to croak," says Richard Sprott, the Ellison Medical Foundation's director, who expects that humans may eventually live as much as 30 years longer, but only in the distant future.

The archives at SAGE Crossroads boast a debate between Sprott and Aubrey de Grey, each exemplifying a polar opposites of approach to aging research and its goals. From where I stand, Sprott is firmly in the full employment act for gerontologists camp, while de Grey is all goal all the time.

There are more people who think like de Grey out there, but I don't think they're talking loudly enough. There are certainly far too many scientists who coast, with no inspiring goals to their work. What is the purpose of research if not to get the damn job done? What is work without purpose? In the case of aging research it's not about making life easy for career scientists, it's about stopping a worldwide, horrendous, terrible, ongoing avalanche of death and suffering.

Even the most widely recognized greatest disasters in human history pale in comparison to natural death. For example, the typhoon that struck Bangladesh in 1970 washed away a million lives. In 1232 AD, Genghis Khan burned the Persian city of Herat to the ground. It took his Mongol horde an entire week to slaughter the 1.6 million inhabitants. The Plague took 15 million per year, World War II, 9 million per year, for half a decade each. The worldwide influenza pandemic of 1918 exterminated less than 22 million people – not even half the annual casualties from natural death. But natural death took 52 million lives last year. We can only conclude that natural death is measurably the greatest catastrophe humankind has ever faced.

It's about building a world in which we can create more of the most valuable commodity there is - time spent alive, healthy and ready to act.

So back to the quoted view of Richard Sprott above. How on earth does one manage to reconcile the belief that it's going to take an age to extend healthy human life by a mere 30 years with even a passing understanding of the present state of science, human knowledge and capabilities? Has he failed to notice the scorching pace of progress in understanding and controlling cells? That biotechnology is now firmly harnessed to exponential progress in computational capacity - and all the benefits that brings? That the laws of physics firmly allow nanoscale machinery capable of replacing and surpassing in every respect all organs and functions of the human body? That the tissue engineers predict a decade or two until we can grow and replace any damaged tissue aside from the brain? That the system biologists think tacking ten years onto healthy life over the next ten years is feasible? That even the tired, slow-moving, government cancer establishment is shooting for victory in a decade?

I want to point out just how outlandish it is to stand in the midst of outright revolution, of wild, foaming progress in bioscience, and say that things aren't going to change all that much. You're out there on your own, Sprott, with few others beside Hayflick for company. The position you hold is extreme and strange to me.

Sometimes there's just too much interesting research out there to link to one by one: inroads against age-related disease; uncovering new and important mechanisms of metabolism; progress in promising classes of future therapy. The list is endless. So sometimes, I throw together these roundups of diverse topics. Let's start with some promising gene therapy work for Parkinson's disease, and move on to Alzheimer's and cancer:

PET scans show gene therapy normalizes brain function in Parkinson's patients:

Brain scans used to track changes in a dozen patients who received an experimental gene therapy show that the treatment normalizes brain function - and the effects are still present a year later.

...

The patients only received the viral vector-carrying genes to the side of the brain that controls movement on the side of their body most affected by the disease. ... The gene makes an inhibitory chemical called GABA that turns down the activity in a key node of the Parkinson’s motor network. The investigators were not expecting to see changes in cognition, and the scans confirmed that this did not occur.

Position emission tomography (PET) scans were performed before the surgery and repeated six months later and then again one year after the surgery. The motor network on the untreated side of the body got worse, and the treated side got better. The level of improvements in the motor network correlated with increased clinical ratings of patient disability, added Dr. Feigin.

A novel way found to prevent protein plaques implicated in Alzheimer's:

Both studies used mice that were genetically engineered to produce human cystatin C as well as abundant amounts of amyloid beta plaques in their brains. The cystatin C bound to the soluble, non-pathological form of amyloid beta in these mice and inhibited the aggregation and deposition of amyloid beta plaques in the brain.

The research shows that cystatin C binds soluble amyloid beta also in the human brain, and suggests that this binding inhibits its aggregation into insoluble plaques in humans, says Dr. Levy. Cystatin C production and body fluid levels vary among healthy individuals and can be influenced by certain hormones, aging, and certain pathological conditions, she says. Furthermore, it was recently demonstrated that a genetic variation in the cystatin C gene in human populations is linked to a greater risk of developing Alzheimer’s disease during aging.

These findings suggest, says Dr .Levy, that even subtle modifications of cystatin C protein levels could affect amyloid beta accumulation and deposition in the brain, thereby modifying disease progression.

I seem to recall research indicating that the rate of turnover of amyloid is very fast, on the order of days. Alzheimer's is not a slow buildup of a compound that can just be removed, but rather a slow increase in the difference between generation and clearance rates. The best answer would be to determine where the fault lies and fix it; some work is aimed in that direction, but the majority aims to introduce new ways to clear amyloid without doing anything to repair the underlying issue. This is, alas, the dominant path in present day medical research.

But on to cancer:

Immune system can drive cancers into dormant state:

Like the older theory, cancer immunoediting suggests that conflict between cancers and the immune system naturally takes place but proposes that three very different outcomes can result. The immune system can eliminate cancer, destroying it; the immune system can establish equilibrium with cancer, checking its growth but not eradicating it; or the cancer can escape from the immune system, likely becoming more malignant in the process.

Until this latest study, evidence for the second outcome was lacking.

...

"We don't think the immune system has evolved to handle cancers," Schreiber notes. "Cancer is typically a disease of the elderly, who have moved beyond their reproductive years, so there probably was no evolutionary pressure for the immune system to find a way to fight cancer."

Schreiber, Smyth and Old speculate that from the immune system's point-of-view, a cancerous cell may look like a cell infected by an invading microorganism. To overcome the safeguards that prevent the immune system from attacking the body's own tissues, the tumor has to have a high level of immunogenicity, or ability to provoke an immune reaction. Cancer cells can reduce their immunogenicity by changing the materials they present to the immune system to more closely resemble those presented by normal tissue. This enables the third outcome of the immunoediting theory: escape.

Equilibrium sometimes may be a more common outcome of tumor-immune encounters than elimination. According to the researchers' theory, some of us may harbor dormant tumors that either developed spontaneously or from exposure to carcinogens. They propose that these quiescent tumors are unleashed only as we age or are exposed to environmental, infectious or physical stresses that cause a breakdown of the immune system.

Greater understanding of the tools already present in our body will be a real boost to fighting cancer, coming in the midst of a revolution in our capacity to alter and make use of those biochemical tools. Improving, retraining and redirecting the mechanisms of the immune system to attack specific cells is a very promising field of research. A good thing too, as we need effective, reliable cures for cancer if we're going to benefit from other strands of healthy life extension research.

I, and no doubt you folk as well, noted the press on the first verified success for therapeutic cloning (also known as somatic cell nuclear transfer, or SCNT) in primates. The research group produced totipotent embryonic stem cells from a starting point of the skin cells of rhesus macaques.

Monkey embryo cloned in major breakthrough

Reproductive biologist Shoukhrat Mitalipov, of the Oregon Health & Science University, and his colleagues reported in the online version of the journal Nature that they have cloned rhesus macaque embryos using DNA from skin cells taken from the ear of a 9-year-old male. The resulting stem cells grew into viable heart and nerve cells, among others.

"This is a giant step toward showing that human therapeutic cloning is possible," said Dr. Robert Lanza, who is trying to produce human embryonic stem cells at Advanced Cell Technology in Worcester, Mass., and was not involved in the research. "It proves once and for all that primate cloning is not impossible ... as many people had thought."

Work has begun to use the new technique to clone human embryos, although the process remains very inefficient. Even so, Mitalipov said, "I am quite sure that it will work in humans."

What is the signficance of this? Well, one has to look at what a source of your own totipotent stem cells can be used for:

Over the past 25 years, mouse embryonic stem cells have been used to create models for scores of human diseases, including cancer, heart disease, obesity, and Alzheimer's. Research discoveries based on these models has led to new drug development and therefore touched countless lives. ... I believe it is only a matter of time before human embryonic stem cells are used in drug development research and become the basis for important new cell therapies.

Producing tissue in specific states to analyze and learn from is just the start. Totipotent cells on tap form an important resource for complex tissue engineering: totipotent stem cells generated from your own cells will be used to produce replacement parts for age-damaged organs and systems in your body in the next few decades.

The bottom line is that increasing control over our cells is a broad highway to increasing control over our healthy life spans. All progress is very welcome.