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Age-Related Diseases: Medicine's Final Adversary?

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AGE RELATED DISEASES
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With millions invested, a strategy in place and progress underway, regenerative medicine is finally closing in on the diseases of late life.

The overall character of medical progress has changed enormously over the past century. We haven't merely made advances -- we've made a partial conquest. The war on infectious disease, for example, has evolved from an invasion into a counter-insurgency operation. Although certain strongholds -- such as HIV and malaria -- remain intact, infectious disease is not fundamentally mysterious any more. Eradicating infectious disease is largely a matter of continuing our steady progress in established fields. This advanced state of medicine is one of the characteristics of our age, which makes it perhaps the most attractive of all ages -- so far -- to live in.

But what are the exceptions? Where does the front line of medicine stop? Behind enemy lines, there still stand all those stubborn illnesses which seem inflicted from within: cancer, Alzheimer's, arthritis, osteoporosis, not to mention more subtle defects such as progressive hearing loss and cognitive decline.

These are the real future challenges of medicine: the infirmities which require the greatest investment of money and effort, and the most original solutions in order to overcome. And they are all particularly prevalent in later life, some of them almost exclusive to old age.

Research into these conditions has indeed received priority and funding from all sectors in recent years -- and, as we might have expected, our insight into these conditions has improved considerably.

But, as things stand, no amount of insight into age-related pathology can be sufficient to develop outright cures. Some diseases are the end results of aging, just as starvation is the end result of fasting. The nature of aging is such that many age-related infirmities are certain to afflict anyone who lives long enough. And this will remain the case, until a technology is developed which ameliorates the general decrepitude of old age which underlies these diseases.

One can, therefore, identify the future direction of medicine by considering the nature of old age itself. What exactly is being taken from us, year after year, from cradle to grave? As time goes by, your hair goes grey, your face gets coarser, you put on weight, you become weaker, more susceptible to disease, and so on. But what do these things have to do with each other?

Fortunately, the answer is not so complex as one might anticipate. Most people think of the science of aging as being very incomplete. It is true that aging as a process is not completely understood (biogerontology, the study of aging, involves many competing theories). But the state of disrepair that aging leaves people in can be observed directly, and in great detail.

A comparison between two perfect snapshots of old and young tissue would provide us with a very multi-faceted damage report. The aged tissue is riddled with "junk" molecules (by-products of normal metabolic functions) in and between cells, which do not dissipate, not even as the body heals and replenishes itself day in and day out. It would also show an accumulation of unwanted cells, and a depletion of necessary cells. All this damage reduces our tissue function, then our organ function, and eventually it kills us.

How this damage accumulates, and how it leads to our demise, are matters of some dispute. But the bare facts of how our tissues alter over time already provide us with enough of a compass with which to chart the future course of medicine.

Suppose we begin by defining old age -- as we must, if we adopt a properly mechanistic and reductionist analysis -- as a lifelong accumulation of tissue damage, which humanity has traditionally viewed as irreparable. Where do we go from there?

In other areas of treatment, such as accidental injury, the list of irreparable tissue injuries has shrunk at a bewildering rate. The past decade has seen numerous breakthroughs in stem cell technology and tissue engineering: the first tracheal transplantation, the creation of inner-ear cells from stem cells, the first artificially grown bladders, heart valves, blood vessels and even trials for the possible use of umbilical cord blood cells to treat brain injury.

The collective term for such therapies is "regenerative medicine": An umbrella term for therapies which restore or regrow damaged tissue, augmenting the body's own innate capacity for self-repair.

In the eyes of regenerative medicine, there is a continuum between accidental injury and age-related pathology. In 2010, for example, scientists from Keele University in the UK began a series of trials for a stem-cell therapy, which aims to permanently repair osteoarthritic knee-joints by stimulating cartilage growth. Osteoarthritis is partly a result of mechanical stress, but it is also sometimes unavoidable for people in late life. Whether it is a result of age or circumstance, the injury itself falls within the purview of regenerative medicine. If we treat old age as an assortment of tissue injuries, with regenerative medicine as a repair-and-maintenance technology, then the practical distinction between age and accident evaporates.

In the near future, we will see a series of applications of regenerative medicine to the conditions of old age, which will give us our first glimpses of what can only be described as rejuvenation. And this sets medicine on a very potent course indeed. Even the partial rejuvenation of aged tissue could result in the dramatic postponement of the diseases of old age. This is more than just a turning point. Any major headway in this direction would be revolutionary.

Since its creation in early 2009, SENS Foundation, a 501(c)(3) registered charity of which I am chief science officer, has been at the vanguard of the effort to expand regenerative medicine into the territory of old age. The acronym in the title, SENS, stands for Strategies for Engineered Negligible Senescence, a strategy devised over several years after a series of consultations between two fields: the science of biogerontology and the technology of regenerative medicine.

By selectively funding research encompassed by this new paradigm, SENS Foundation (SENSF) is laying the foundation for a whole new industry. Its modus operandi is simple: Identify and categorize the tissue damages that intensify with age, and then do everything in our power to expedite the development of a therapy for the repair of each.

SENS has a history of philanthropic funding going back well before the creation of SENSF. Our most high-profile recurring donor is the Paypal co-founder and early Facebook investor Peter Thiel, who pledged $3.5 million to the project itself in 2006, and continues to give periodic support.

But over the past year we have broadened our range of endeavours, expanded our influence, and begun to cooperate more fully with the rest of the industry. In 2010 we joined forces with the Wake Forest Institute for Regenerative Medicine (the team responsible for many of the above-listed breakthroughs in organ regrowth), in order to take best advantage of our overlapping objectives. In December 2010, we received an additional $600,000 from the Arizona-based entrepreneur Jason Hope, which we are investing in new prjects, to add to the range of projects already underway in our research centre in Mountain View, California and in university labs across the county.

With these extra funds, new alliances and additional facilities, SENSF will by late 2011 be pursuing at least one major research program within each major category of age-related tissue damage which we have identified.

What are these categories? There are seven in all -- seven alterations in and around cells, which distinguish the old from the young, each with a corresponding SENS research theme, which I will expand on in subsequent articles. It is through the advancement of these research strands -- a comprehensive attack on the diseases of old age from seven directions at once -- that medicine will make its final conquest.