Fight Aging!

Irina Conboy is on the SENS Research Foundation's advisory board and is one of the more frequently noted scientists presently working on heterochronic parabiosis and related research. These scientific programs aim at identifying age-related changes in important signal proteins circulating in the bloodstream, with parabiosis being where it all starts: link the circulatory systems of an old and a young animal and observe benefits to measures of health in the elder of the two. This happens because old tissues are exposed to a young blood environment. Once specific proteins in the blood are identified as being of interest, then researchers move on to attempts to alter amounts of these proteins in circulation in old animals. They are in search of the basis for therapies that might make cells and tissues in an old individual behave as if they were younger, despite the damage they have suffered.

The main thrust of this research could probably be considered a branch of stem cell medicine. The signals that differ between young and old tissue appear to be involved in regulating the activity of stem cell populations, and thus the degree to which tissues are maintained, kept supplied with fresh new cells. It is well known that stem cell activity declines with age. Much of the present panoply of stem cell therapies consists of what are, when it comes down to it, ways to bolster regeneration and tissue maintenance in old people. Stem cells transplanted into patients appear to achieve at least some of their beneficial effects by altering the balance of signal proteins in their environment. So why not a future in which the cells are done away with and the therapy consists of directly manipulating protein levels? The only thing needed for that to come to pass is a much better understanding of the signals themselves and how they control cell behavior.

The caveat for all of this is that as an approach it really doesn't address the underlying causes of aging at all. It addresses a consequence of cellular damage without repairing the damage itself. Revving up the activity of a damaged engine obviously bears risks. The greatest risk from a theory point of view is cancer: that damaged cells are doing more has an obvious consequence. In practice, more has been achieved in the field of stem cell medicine and with less cancer as the outcome that was feared at the outset. There may be a fair degree of room in our evolved biology for more regeneration in a damaged system, who knows. Equally these bounds and balances may be very different for short and long-lived species, and so it is an open question as to the degree to which we can trust results in laboratory mice today, even following on from consistency in past results in laboratory mice now translated into human stem cell therapies.

Still, we need stem cell medicine for the old. Stem cell populations will need restoration and repair regardless of success in the rest of the rejuvenation toolkit, as there will be old people awaiting treatment when these therapies are introduced. It is another open question as to whether sufficiently good prevention of other forms of damage will mean that stem cell populations never decline in an individual who has undergone period use of repair therapies since childhood, but that is hardly the most pressing issue in front of us. The first and initial goal of building treatments for aging is to save the people who are old when those treatments arrive.

Engineering the End of Aging

For over a decade, Conboy and her colleagues at UC Berkeley have been searching for ways to slow down or even reverse aging. Their latest discovery - a small-molecule drug that restored brain and muscle tissues to youthful levels in old mice through stem cells - signalled that the prospect of anti-aging therapy for humans may be on the horizon. Published this May, the discovery has been called "fountain of youth" or the "secret to eternal youth" by the media. Comfortably clad in an oversized hoodie, Conboy burst the bubble in her high-pitch, Eastern European accent: Sorry, the drug won't keep us young forever, and we will all eventually die. But what her research hopes to accomplish, Conboy said, is a painless, cost-effective way to live when we are old.

Aging-related diseases like adult-onset diabetes, cancer, Alzheimer's, and Parkinson's disease kill millions every year while draining the economy of billions of dollars on health care costs, and a treatment that keeps people healthier in old age would cut the costs significantly down. A drug that tackles these diseases at its root would also give people more agency how they choose to live late in their lives. "Aging is a synonym with diseases," Conboy said. "When we are young, we don't have these diseases. But when we are old, it doesn't matter what background or gender or culture, we all have them. If we can better understand the aging process, then we don't need to have different hospitals, departments, and institutes that deal with each disease."

The drug, known as Alk5 kinase inhibitor, target a growth factor called TGF-beta1 pathway which, at old age, overproduce itself and inhibits other pathways to stimulate stem cells. As our body breaks down over time, stem cells - which are responsible for repairing the body and live huddled together in pockets called niches - are prevented by TGF-beta1 from doing its job. As the body ages, however, the TGF-beta1 begins to overexpress itself and become a deterrent for yet unknown reasons. What the Alk5 kinase inhibitor sought to do was not rid the body of the pathway but rather regulate it by attaching itself to the pathway and dulling its signal asking for more expression. Now with the TGF-beta1 down to youthful levels, stem cells are able to freely repair the body.

"I look at it as more promising than anything," said Hanadie Yousef, the lead author of the Oncotarget study and currently a postdoctoral scholar at Stanford University. "When I was starting graduate school five years ago, there was absolutely nothing known about how aging actually happened. The field is growing so rapidly that I would bet within the next decade we'll see effective anti-aging therapeutic methods." With the probability of anti-aging therapy on the horizon, death may take a different shape in the future. Death, as Conboy's team hoped to accomplish, would no longer come with pain or suffering at some hospital with wires and machines keeping the body alive. Instead, death will come by more natural causes such as cardiac arrest or a stroke - a relatively quick way to die than fighting years against cancer or similar diseases. "I hope we'll just die in our sleep with no cancer or disease eating up our organs," Yousef said. "The goals of my colleagues and I are not to live forever. Instead of becoming old and becoming a burden on society, we can age ourselves more with integrity."

Persuading researchers to work on treating aging at all has been the major battle of the past fifteen years. We've come a long way when postdocs can now talk in public about treating aging without fearing for their future careers. From here we can build, grow the number of researchers who are willing to aim higher - at rejuvenation, radical life extension, and a complete end to aging. No illness, no loss of vigor or health, and consequently no age-related deaths. That is the future we'd like to see more people working towards.