Fight Aging!

The past few years have seen very encouraging progress in rejuvenation research and the commercial development of therapies. Senolytic treatments capable of clearing senescent cells, one of the root causes of aging, are moving towards human trials, with a number of companies hard at work on therapies at various stages of development. The animal data continues to roll in, and continues to look very promising, with senescent cells shown to contribute directly to an increasing number of age-related conditions. In addition the established mainstream efforts to remove age-related protein aggregates such as amyloid-β, tau, and α-synuclein are broadening the number of targets and strategies, and in addition are coming closer to success after many years of failed trials. Amyloid-β has finally been cleared from human brains in a clinical trial, and many of the newer approaches to reducing levels of various forms of aggregate seem quite promising in animal and human studies. These aggregates are another of the causes of aging and age-related disease, there is a real sense that the present time is a tipping point in this area of medical development.

As you've no doubt noticed, this zeitgeist has been reflected here at Fight Aging! in an increased consideration of startup companies and the early steps in translation of the most important lines of research from laboratory to clinic. Similarly, groups like the SENS Research Foundation and Methuselah Foundation have also focused a sizable fraction of their attention on this part of the development process. See, for example, the Rejuvenation Biotechnology conference series of the past few years that brought together academia and industry, and the Methuselah Fund launched this year.

Yet it is important to remember that all of this welcome progress, the move from non-profit research to for-profit development, with human trials on the near horizon, is only taking place for a fraction of the areas of science and technology required for comprehensive human rejuvenation. Yes, senescent cell clearance is well under way now, and both protein aggregate clearance and cell therapies seem well funded and pointed in roughly the right direction. But what about therapies to address glucosepane cross-links, a cause of blood vessel stiffening and bone fragility; or the mitochondrial DNA damage and consequent mitochondrial malfunctions that are implicated in such a wide range of age-related disease; or the scores of other forms of metabolic waste found in lipofuscin and amyloids? What about the decline and disarray of the immune system; what about steering the cancer research community towards universal therapies based on prevention of telomere lengthening, applicable to all cancers?

Aging has multiple root causes. Fixing one root cause - say if senescent cell clearance progresses stupendously well, and we're all having 75% of our senescent cells removed at a $15,000 price tag for a form of FOXO4-p53 interdiction via medical tourism sometime around 2021 - has a limited upside because it is only one root cause. Each of the categories of damage outlined in the SENS view of aging is ultimately fatal in and of itself, though it is far from clear which are more or less important to any specific aspect of aging. Remove just one and some forms of mortality will decrease considerably. Others might be postponed. Yet more might be only slightly affected, however, and they will still kill you. The upside of partial rejuvenation is nonetheless a much better prospect than anything that can be done with yesterday's medical technology, but it is only the opening chapter, not the whole story.

Yes, we should do what we can to help commercial development: invest if we are able, cheerlead and publicize if we can. But we can't become distracted from the important lines of research still underway in their earlier phases, prior to the point at which they can make the leap to startup companies, and in need of philanthropic support to move ahead. Despite the considerable evidence supporting the SENS view of aging as damage and rejuvenation as damage repair, the research community and institutional funding sources continue to give little attention to lines of work that are capable of becoming just as large and just as important as senolytic treatments to remove senescent cells. Prior to 2011, senescent cell clearance was another of those ignored lines of work: that success can and must be repeated for the others.

Of the less well supported lines of work that could turn back aging, those closest to realization appear to be: immune system restoration via some form of targeted cell killing; immune system restoration via regeneration of the thymus; pharmaceutical clearance of glucosepane cross-links; and allotopic expression of mitochondrial genes. These are all still at the stage wherein the charitable donations that we as a community can raise for specific projects, or provide to the SENS Research Foundation, make a real difference. These projects all appear to me to be a few years from reaching viability for commercial development, on average, and they all scrabble for needed funding to one degree or another. All of these should produce similar overall degrees of benefit to those produced by senolytic therapies, albeit in very different ways. This is where we can accelerate progress towards the near future of greater human longevity, just as we have in the past.

Growing success in portions of the broader field of rejuvenation research should encourage us: it shows that the support we have provided over the last decade or more has worked. Things are moving, the wheel turns. We can do the same for the parts of the field that have yet to attract the attention they need, have yet to reach the same level of enthusiasm and funding. Give it some thought.