Noninvasive Neonatal Thymus Graft into the Axillary Cavity Extends the Lifespan of Old Mice:

Neonatal thymus grafts exert a rejuvenating action on various immunological and nonimmunological functions found altered in old mice. Commonly, half of a thymus is grafted under the kidney capsule. The invasiveness of the surgical procedure and the use of limited thymus tissue may explain why precedent survival kinetics remain unaffected.

In this trial, we grafted two neonatal thymi into the axillary cavity of old mice, thus reducing the invasiveness of the intervention and increasing the amount of grafted neonatal tissue. Using a Piantanelli parametric model of survivorship, we found a significant change in mortality rate between the two groups (thymus graft and controls).

You might recall that the degeneration of the thymus over time - a process known as involution - is one of the limits placed upon your immune system. The thymus is the source of T cells, the workers of the active immune system. Considered within the framework of a normal life span, the thymus spins up early, churns out your population of T cells while you are a child, and then largely shuts down once you reach adulthood. You are left with what is essentially a fixed population of immune cells to see you through the rest of your life. Which is a simplification of a more complex set of processes, but close enough for our purposes here.

The degenerating effectiveness of an aging immune system results in large part from the limited T cell population: it runs out of T cells that are not already assigned to specific tasks. Over the years, exposure to persistent but usually harmless viruses like cytomegalovirus (CMV) chews up your quota of T cells, leaving too few to effectively defend against new threats, destroy senescent cells, or destroy cancerous cells before they can form a tumor. So you suffer, and the degenerations of aging are accelerated.

One possible way to deal with this problem and restore the immune system to a more youthful capacity is to destroy the clutter. Use targeted therapies of the type under development by cancer researchers to kill off the T cells that are dedicated to fight CMV, and then repopulate your immune system via stem cell medicine. Or, more radically, completely destroy and then recreate your immune system, wiping the slate clean. This second method has already been achieved in early trials for autoimmune diseases.

But another approach is to simply boost the number of immune cells circulating in the body. I've discussed rejuvenation of the thymus through tissue engineering or other techniques in the past - essentially gearing it up to generate more T cells than would normally be the case. Transplantation of young thymus tissue, as the researchers in the paper quoted above have demonstrated, is one way of validating this approach. The immune system is so critical to resisting various forms of progressive cellular and other biochemical damage in the body that it is not unreasonable to expect at least some enhanced longevity to result from its restoration.

Basso, A., Malavolta, M., Piacenza, F., Santarelli, L., Marcellini, F., Papa, R., & Mocchegiani, E. (2009). Noninvasive Neonatal Thymus Graft into the Axillary Cavity Extends the Lifespan of Old Mice Rejuvenation Research DOI: 10.1089/rej.2009.0936

Declining Death Rates Reflect Progress against Cancer

The success of the "war on cancer" initiated in 1971 continues to be debated, with trends in cancer mortality variably presented as evidence of progress or failure. We examined temporal trends in death rates from all-cancer and the 19 most common cancers in the United States from 1970-2006. ... Progress in reducing cancer death rates is evident whether measured against baseline rates in 1970 or in 1990. The downturn in cancer death rates since 1990 result mostly from reductions in tobacco use, increased screening allowing early detection of several cancers, and modest to large improvements in treatment for specific cancers. Continued and increased investment in cancer prevention and control, access to high quality health care, and research could accelerate this progress.

That there is debate over the effectiveness of funding for cancer research is somewhat a function of slow and steady progress rather than sudden leaps in technology both inspiring and obvious in their magnificence - which will always be the case, people being people. On the other hand, that cancer research is so dominated by government funding has no doubt led to great inefficiency and much borderline or useless work that should not have taken place; everything touched by government funding eventually turns into a low-motivation jobs program and sinkhole for graft, no matter how urgent the cause.

The dry conclusion of the paper is a conservative projection of present trends into the future, something which we should instinctively doubt given the nature of the era. Accelerating change is everywhere: any field connected in some way to computing power is rushing forward, ever faster with each passing year. Biotechnology and its application to medicine is no exception, and the next generation of cancer therapies, based on targeted nanoparticles and identification of cancer biochemistry, will be very much more effective than presently widely available medical technologies.

The existence of a technology platform that can be used to efficiently and safely kill very specific cell types reduces cancer to just another information problem in biotechnology: what do the cells you want killed look like? How is their chemistry different from that of other cells? What is the specific molecular marker I am looking for here? These questions are dead center in the fast lane of life science. The therapies based upon this technology will be as far beyond chemotherapy as chemotherapy is beyond no treatment at all.

Jemal, A., Ward, E., & Thun, M. (2010). Declining Death Rates Reflect Progress against Cancer PLoS ONE, 5 (3) DOI: 10.1371/journal.pone.0009584

We can see aspects of this process happening now in the field of stem cell research. The real action in terms of foundational growth and application of new science is taking place outside America and Western Europe. Absent large changes in the tenor and breadth of medical regulation in the US, the future of your health will be found in Asia, because that will be where the safe, reliable, low cost therapies exist.

A couple of articles I noticed recently are illustrative of the infrastructural development taking place in that region of the world:

Miracles of Science in Regenerative Medicine

The Manipal Institute of Regenerative Medicine (MIRM), a new initiative of Manipal University, has been created to transform stem cell science into reality by bringing together a group of outstanding scientists and providing them with an exceptional research environment. India is identified as one of the forerunners in stem cell research and MIRM is the first academic Institute in India to impart focused training in stem cell biology.

ISSL to invest Rs 50 cr to set up stem cell speciality hospitals in metros

International Stemcell Services Limited (ISSL) which is engaged in stem cell clinical application and banking services is planning an investment to the tune of Rs 50 crore. The funds will be utilized to establish dedicated stem cell speciality hospitals in major cities and open up Departments of Regenerative Medicine in existing hospitals. The company would chip in a portion of the funds from its internal accruals and the remaining will be raised through financial institutions. Presently, ISSL has a opened a facility at the St Theresa’s Hospital, Bangalore which is equipped with a Philips endura C-arm for transplantation of stem cells. Its Mumbai centre is a class 10,000 cGMP facility, which caters to the western parts of the country.

Pahang going ahead with stem cell research hub

The Pahang government [in Malaysia] will proceed with plans to set up a stem cell research hub despite questions being raised on the effectiveness of stem cell treatment, Mentri Besar Datuk Seri Adnan Yaakob said. Adnan said the state government was aware of questions being raised both here and abroad over the authenticity of claims that stem cells could be used to cure a number of ailments. He said some quarters felt that more research should be carried out to determine if the treatment actually worked but he noted that many individuals claimed that their condition had improved following such treatment.

This sort of thing will continue, and the pace will pick up.

Complexity is interesting to look at, however. I recently noticed a paper that investigates the details of a known trend in metabolism that takes places as people age:

This study investigates age-dependent changes in resting metabolic rate (RMR) considering changes in body composition and fat distribution within the longitudinal study on nutrition and health status in an aging population in Giessen (GISELA), Germany

...

Approach 1: RMR correlates significantly negatively with age in women and men. Considering fat free mass, fat mass, and [weight and height], age proved to be a significant predictor of RMR in both sexes in multiple regression analysis; RMR falls by 11.2 kJ/d and 34.1 kJ/d per year in females and males, respectively.

Approach 2: In males but not in females RMR decreases significantly in the course of the follow up. After ten years measured RMR is significantly lower than expected RMR predicted on the basis of body composition and fat distribution in females and males. Deviations correspond to a decline in RMR by 11.4 and 27.5 kJ/d per year independently of changes in body composition and fat distribution.

Approach 3: Results of the mixed linear model show that RMR decreases in the course of aging in both women and men; after considering changes in body composition and fat distribution respective decreases were 8.7 and 30.7 kJ/d per year.

...

These results indicate that the decline in RMR with advancing age cannot be totally due to changes in body composition.

Which is interesting. It has been known for a great many years that metabolic rate declines with age in a fairly predictable way, when averaged across populations. It would not be unreasonable to attribute this change to the way in which the gross details of the body change with age, on average - less muscle, more fat, for example. But not so, apparently. Other, more subtle processes are at work.

One might think of calorie restriction in this context. It is known that metabolic rate declines with calorie restriction in a variety of species, which includes primates. It is also generally the case that older humans eat less than they did when younger.

One might also consider this slowing down of metabolic rate with age as one a part of the evolved cancer suppression processes that take place in the body. Less biological activity, all other things being equal, should lead to a lower risk over time of generating cancerous mutations.

Interestingly, a combination of resting metabolic rate and a measure of the composition of mitochondria have been shown to correlate extremely well with the maximum life span recorded in varied species of mammal. These two items, the pace of your biology and the degree to which your mitochondria resist damage, appear to be the most important intrinsic determinants of the outer limits of natural life span.

Natural life span is something we'd all like to do away with, of course; researchers have been working on that task in one way or another since the dawn of humanity. Our ancestors focused on extrinsic determinants of life span - the food, the things with claws and large teeth, the diseases. What sets our era apart is not just that we are equipping ourselves to see the true complexity and operation of our biology, but that we are equipping ourselves to change it and even repair it. The days of degenerative aging and intrinsic outer bounds to human life span are numbered.

Luhrmann PM, Edelmann Schafer B, & Neuhauser Berthold M (2010). Changes in resting metabolic rate in an elderly german population: cross-sectional and longitudinal data. The journal of nutrition, health & aging, 14 (3), 232-6 PMID: 20191259

Breakthrough Reveals Blood Vessel Cells Are Key to Growing Unlimited Amounts of Adult Stem Cells

In a leap toward making stem cell therapy widely available, researchers at the Ansary Stem Cell Institute at Weill Cornell Medical College have discovered that endothelial cells, the most basic building blocks of the vascular system, produce growth factors that can grow copious amounts of adult stem cells and their progeny over the course of weeks. Until now, adult stem cell cultures would die within four or five days despite best efforts to grow them.

Predicting the Fate of Stem Cells: New Method Decodes Cell Movements, Accurately Predicts How Cells Will Divide

Researchers at Rensselaer Polytechnic Institute have discovered a new method for predicting - with up to 99 percent accuracy - the fate of stem cells. ... In order to achieve successful stem cell-based therapies, researchers require access to large amounts of specific cells. This has proven difficult, as there are currently no methods for controlling or manipulating the division of bulk quantities of cells. When stem cells or progenitor cells divide via mitosis, the resulting daughter cells can be self-renewing or terminal. A self-renewing cell will go on to split into two daughter cells, while a terminally differentiated cell is fated to be a specific, specialized cell type. Researchers want the ability to influence this division in order to produce large volumes of the correct type of cells.

Both of these lines of research feed into the search for low-cost and reliable sources of specific cell populations, and ways to quickly generate those sources from a patient's own cells. Much of the progress in this field has yet to happen, as the real free-for-all of experimentation and implementation only gets underway once costs in time and money become low enough. Everything that has happened in the fields of regenerative medicine and tissue engineering over the past decade was just a warm up in comparison to what's ahead.