Studying SENS

 
More and more people are coming to realize that we now have many of the tools we need to develop effective treatments for age-related diseases: all that’s needed is to unleash the locked-up potential of our scientific resources. The most important resource that needs to be mobilized is a new generation of scientists, driven by the vision of a world finally freed from biological aging.
 
As this awareness has spread, the Foundation has frequently heard from students and students-to-be, who want to know what they should be doing to position themselves for a career in rejuvenation biotechnologies: the science of repairing the cellular and molecular damage that causes the diseases of aging. The surge in requests is inspiring, and almost overwhelming. Whether they’re seniors in high school or engineers looking to drop successful careers to go back to school and take up the biotechnologies of rejuvenation, these “Young Turks” will be key to changing the research agenda from within, as research laboratories all over the world receive a transfusion of new blood that revives the hopes of millions.
 
Maybe you’re one of these students. Where can you start?
 
Gearing Up
 
If you are still in high school, get a head start by taking the most advanced biology and chemistry classes available to you. Supplement your classwork with more advanced material on cellular and molecular biology: for example, Essential Cell Biology or the more advanced Molecular Biology of the Cell (an earlier edition of which can be read online for free).
 
Whatever your current level of knowledge in the life sciences, familiarize yourself with the specific biotechnological platform of SENS. The details of this platform are explained in clear, accessible language in Ending Aging: The Rejuvenation Breakthroughs That Could Reverse Human Aging in Our Lifetime, a popular science book by Foundation Chief Science Officer Dr. Aubrey de Grey with research assistant Michael Rae. (Royalties are entirely turned over to the Foundation to advance the new anti-aging science). The book will frame what you learn and guide your choice of classes and later career. While aimed at a popular audience, the level of detail makes this book still the best place to get a grounding in rejuvenation engineering, even if you already have enough life sciences background to navigate technical papers.
 
A Broad Foundation
 
The science of rejuvenation is advancing rapidly, so no narrow listing of specialized classes can give the flexibility you’ll need to match your own strengths to the needs of research in 4 to 10 years. Instead, select your classes to ensure a solid, broad background in molecular and cellular biology while meeting your school’s program requirements for an undergraduate degree in life sciences. Sit down with a student advisor for help with this. If you have time and mental energy, audit additional courses to get the benefits of a broader background knowledge without the liability of needing to memorize additional details for exams. Study hard, get good grades, and learn the skills of laboratory work wherever you can: the knowledge and skills will serve as your foundation for later work, and will also be important to gaining scholarships and graduate positions.
 
But remember that the point of your degree is not to have a piece of paper on the wall, but to use it as a tool to further your studies: in the words of Mark Twain, never let your schooling get in the way of your education. Your initial major is a foundation, not an end-all career decision. Get some time in the life science community at your school along with the books: network with your professors, especially in areas that interest you, to establish contacts, references, and mentoring relationships.
 
More Technical Biogerontology
 
After reading Ending Aging, move on into more technical biogerontological literature as your base knowledge in life sciences expands. A basic biogerontology foundation could be laid with such books as The Handbook of the Biology of Aging by Edward J. Masoro and Steven N. Austad (Eds), Geriatric Bioscience by David Hamerman, Understanding Ageing by Robin Holliday, and Why We Age by Steve Austad (less for its value for advancing rejuvenation science per se - its focus is a detailed and very readable explanation of why “programmed aging” theories are incompatible with evolutionary theory - than for an enjoyable and wide-ranging review of what is widely held in the field by a sympathetic and highly reputable scientist). Additionally, it will be extremely useful for you to read Dr. de Grey's technical papers on rejuvenation engineering (and of course cited experimental work, clinical trials, etc), most of which are available in submitted manuscript form on this website.
 
To keep abreast of developments in the field, there are several excellent biogerontology journals, most notably Rejuvenation Research, the “international, interdisciplinary, peer-reviewed academic journal that covers all aspects of biology and biomedicine relevant to the combating, and ultimately the reversal, of age-related physiological and cognitive decline in nonhuman species and eventually in humans,” of which Dr. de Grey is Editor-in-Chief. If your institution has a subscription, you should be able to get direct online access – and if not, you can submit a request to your school library. This requires the library’s contact information, preferably for the collections department, which is usually available on the ‘contact’ page, or by asking a librarian about the right person to contact about a subscription recommendation. An institutional subscription to Rejuvenation Research not only gives you access to the journal, but also helps to disseminate high-quality biomedical gerontological research at your institution.
 
Undergraduate Research Projects
 
Most scientists-in-formation don’t start doing actual research until graduate school. If you have the motivation to start getting your hands dirty as an undergrad, SRF Education is here to help make it happen! Most schools in the American university system have “Independent Studies” and “Advanced Honors” programs, through which undergrads design and execute their own research projects in consultation with faculty members. Such programs are a fantastic way to distinguish yourself, to gain valuable research experience, and potentially to make contributions to rejuvenation engineering before you even get your BSc! The institution supports these efforts with lab space, basic materials, and a small stipend for expenses, and awards academic credit. SRF Education can leverage these programs with information, support, and even funding in the form of materials grants. The program also awards grants to students working on their own aging- and rejuvenation-related projects in university labs outside of independent study programs, and provides small scholarly awards to its most accomplished students each semester. Keep in mind that, while hands-on research in a lab is priceless, students who are not actively working in a laboratory can always work on one of SRF Education's literature review projects.
 
(Post)Graduate Research
 
Some of your best opportunities to contribute to the actual reversal of biological aging in humans (as opposed to doing a lot of descriptive and curiosity-driven work with no clinical endpoint for a generation) are likely to come in labs that are not “officially” doing biogerontology at all, but stem cell research or mitochondriology. Exactly where to go will depend on what areas of research appeal to you most and to which you have the most aptitude. Specific areas where key work exists to be done by someone with the right motivation include:
 
Allotopic expression of Mitochondrially-Encoded Proteins (MitoSENS): Several labs are working on this, including rapidly-advancing work at SENS Research Foundation-funded efforts of Dr. Marisol Corral-Debrinski‘s lab at the Foundation Voir et Entendre in Paris, as well as earlier-stage work using a different technique (inteins to reduce protein hydrophobicity) in Spain in Dr. Antonio Enriquez’ Genoxphos Group at the Departamento de Bioquimica y Biologia Molecular y Celular, Universidad de Zaragoza. In North America, Dr. Peter Schultz at the Scripps Research Institute has just come out of nowhere with a new AE advance; also, Dr. Judd Aiken, whose prior lab at the University of Wisconsin had been doing stellar work on the role of mitochondrial mutations in aging for a over a decade now, has now moved on to another regenerative engineering challenge: prion diseases, at the Centre for Prions and Protein Folding Disease (CPPFD) at the University of Alberta. But Dr. Aiken has a longstanding interest in AE, and could yet be interested in a program by a well-motivated, promising young investigator.
 
Ablation and Reprogramming of Death-Resistant Cells (ApoptoSENS): During 2009/10, SENS Research Foundation launched a project to develop a procedure for clearing anergic T-cells from the blood of mice, and potentially thereafter in primates, by Dr. Janko Nikolich-Zugich, Chair of the Department of Immunobiology and Co-Director of the Arizona Center on Aging at the University of Arizona. Dr. Judith Campisi, a prominent researcher in this area with labs at the Lawrence Berkeley National Laboratory and the Buck Institute, has been doing preliminary research to develop an ablation strategy for “senescent” cells since at least the first SENS conference (see the Proceedings).
 
AGE-Breaking Small Molecules (GlycoSENS): The biotechnology firm Synvista Therapeutics (formerly Alteon) pioneered the first AGE-breaking drug, alagebrium chloride, but its clinical impact has been limited, probably due to the rarity of its target in humans. There is relatively little going on to advance new AGE-breakers through medicinal chemistry or directed evolution; we have therefore identified this as possible critical-path work, and have initiated a project at a new lab at Cambridge University under Prof. William Bains. Labs more experienced in this area, such as the Houk Group at UCLA and the Baker Laboratory at the University of Washington, are better-positioned to do this work, having a start-to-finish system for the rapid design of catalytic molecular medicines that could be turned to the design of a glucosepane-breaker, and have expressed some tentative interest; if you have drive and talent in this area, it might be worth contacting them to explore the possibility of working with their tools on a glucosepane project.
 
Immunotherapy for Extracellular Aggregates (AmyloSENS): There are now numerous pharmaceutical companies and academic laboratories around the world racing fiercely to develop active and passive vaccines against beta-amyloid as a disease-modifying therapy for Alzheimer’s disease. Elan Pharma is the most advanced: after safety problems with their first, active vaccine, their new monoclonal antibody passive vaccine Bapineuzumab (AAB-001) is poised to be bumped up into early Phase III clinical trials. Close rivals include Eli Lilly’s LY2062430 and Baxter Biosciences’ intravenous immunoglobulin (IVIg) preparation Gammagard. SENS Research Foundation is currently in discussion with leading researchers in this field with a view to developing an immunotherapy-based system to remove the transthyretin (TTR) deposits responsible for senile cardiac amyloidosis.
 
Transgenic Microbial Hydrolases for Intracellular Aggregates (LysoSENS): Following the completion of a cycle of SENS Research Foundation-funded work in the labs of Dr. Bruce Rittman at The Biodesign Institute at University of Arizona, this work has now moved into SRF's research center (which is also a hub for volunteer scientists-in-training to spend informal training sabbaticals); extramural work continues at Rice University under the direction of Dr. Pedro J. Alvarez, Chair of Civil and Environmental Engineering at Rice University; and Dr. Janet Sparrow at Columbia.
 
Cell Replacement and Tissue Engineering (RepleniSENS): Because the potential of cell therapy as a treatment for the diseases of aging is widely accepted, these technologies are already robustly supported by many governments around the world, and in all probability this will shortly extend fully to the United States. As a result, while we would certainly not wish to strongly counsel against pursuit of this key strand of rejuvenation engineering biotechnology, it is not as high a priority for the Foundation: most young researchers will be more able to contribute to the progress toward a comprehensive panel of age-reversing biotechnologies by pursuing another SENS strand. However, if you are exceptionally drawn to this strand, or feel that you have an unique opportunity to work on a project that engages you, we strongly encourage you to pursue it! (That said, SENS Research Foundation has now reached agreement to test thymic cell therapy for immunological regeneration in aging mice, beginning in 2010; this exception is justified by the specific gap in this intervention within the field).
 
SENS Research Foundation's laboratory facilities: As noted above, the Foundation now carries out critical-path rejuvenation biotechnology research at our in-house research center in the San Francisco Bay Area. Though research is primarily carried out by SENS Research Foundation staff researchers, most of whom have postdoctoral experience, volunteers - even undergraduates - are a fixture at our lab. If you can travel to the Bay Area and support yourself for a short or long stay, a stint at SRF's research center can be a chance to develop your skills as a researcher in an environment uniquely centered on a head-on assault on the degenerative aging processs, and to make a real contribution. If you are interested, please contact SRF's research center directly.
 
The Future is Open for Rejuvenation Research
 
As you can see from the above there is a lot of work to be done, and that’s only likely to expand; moreover, as funding becomes available, the Foundation will be expanding its direct funding and ‘pump-priming’ of rejuvenation engineering research, focusing on existing bottlenecks in the process. Some of our priorities, based on the state of research today, are laid out on the individual webpages for each of the seven strands of SENS (linked above). The Campaign Against Aging also has a useful summary, which includes work being conducted by other organisations.
 
So long as the Foundation’s current rate of scientific progress and of funding expansion continues (or accelerates), the ensuing developments in the various planks in the comprehensive platform of rejuvenation engineering science will create new opportunities for today’s first-year undergraduates by the time they earn their BScs (let alone are postdocs!). But the ideas laid out above should help new researchers-in-formation prepare themselves for a productive research career in whatever specific field most engages his or her talents and interests, and indeed to discover their niche.
 
We’ve learned from experience that young researchers who are genuinely passionate about curing aging, and haven’t just ‘fallen into’ biogerontology or other rejuvenation-relevant work because of their grad advisor, or a convenient funding opportunity, etc, make enormously disproportionate contributions to progress when academic work is leveraged by relatively modest Foundation seed money.
 
For researchers with native talent with a drive to contribute to the biotechnologies of rejuvenation, the great challenge will not be to find scientifically stimulating and worthwhile work, but to avoid being drawn into work that is of genuine scientific value but that is only loosely related to breaking the bonds of aging. When a highly respected and well-funded senior investigator invites you to take on an intellectually stimulating project that will serve as a clear springboard into a secure position, it will take courage for you to remain single-minded in your vision to help bring an end to age-related suffering and death.
 
The critical career decisions that would-be biomedical gerontologists must make will not be centered around the generation of knowledge or building applications as a pure scientist, but strategic decisions about navigating a vast, complex, evolving, and partially unknowable scientific landscape of the world, including its internal politics and human relationships, making decisions based on what will lead most rapidly toward the repair of the cellular and molecular damage of aging. This first generation of dedicated rejuvenation bioengineers will have our future in their hands, as their career decisions and ensuing research determine how soon the first breakthroughs are achieved. Once they have led the way, the gravitational pull established by their leadership could draw in their colleagues; the research agenda could shift, accelerating progress and eventually ending the blight of age-related disease and disability.
 
Michael Rae
Research Assistant to Dr. de Grey