annual report april 2013 contents Introduction . 2 Research Summary . 3-10 Outreach . 11-14 Education . 15-16 Finances . 17-18 sens research foundation - 110 Pioneer Way, Suite J - Mountain View, CA 94041 - USA phone: 650-336-1780 - fax: 650-336-1781 - www.sens.org Chief Executive Officer Board of Directors © 2013, SENS Research Foundation Mike Kope Jonathan Cain All rights reserved. Kevin Dewalt Chief Science Officer Bill Liao No part of this material may be reproduced without specific Aubrey de Grey Barbara Logan permission from SENS Research Foundation. James O’Neill Chief Operating Officer Kevin Perrott SENS Research Foundation’s federal employer ID number is 94-3473864. Because SENS Research Foundation is a 501(c)(3) Tanya Jones reimagine Mike Kope non-profit, your donation may be tax deductible. A world free of age-related disease “The biggest driver of our long-term debt is the rising cost of healthcare for an aging population.” – President Barack Obama’s 2013 State of the Union address1 . The United States will spend more than one trillion dollars There is only one charity in the world doing the work – on healthcare for seniors this year 2. Heart disease, the scientific, educational, and outreach-based – to address greatest of the US’s health problems, has recently become those causes . the developing world’s biggest killer as well .3 The economic crisis noted in the President’s decisive comment is not Please, take a moment and reimagine aging with us . ours alone: it is everyone’s . Meanwhile, the worldwide suffering caused by the diseases of aging remains too Start by imagining a cure for cardiovascular disease 5. high to measure by any standard . Bypass surgery is obsolete, and heart attacks and stroke no longer occur . It may not be Of course the problem is easy to find such a cure, but not unnoticed . There is it is possible, and that is why an immense amount of SENS Research Foundation research being poured exists . Treatments that could into the development of actually, truly, effectively treatments for age-related repair the damage behind disease . Gerontological heart disease -- not just treat research foundations and symptoms or stave off the institutions are increasingly inevitable -- could absolutely focusing on translational emerge, given the right research, and the word research and development . It ‘healthspan’, once a bit is simply that this particular Aubrey de Grey - CSO Mike Kope - President, CEO eccentric, is now in wide branch of biomedical R&D is use . critically under-funded . We’re changing that 6. This is all good news, in itself, and we ourselves have been Now try to imagine a cure for any age-related disease: a member of the Healthspan Campaign since its inception .4 Alzheimer’s, diabetes, macular degeneration, arthritis, But an expressed focus on healthspan does little to define a perhaps even cancer . It isn’t impossible . But the work biomedical organization’s work – enhancing human health required to bring about these cures is, again, critically is, after all, the fundamental purpose of medicine itself . To under-funded . really do something about aging, we need to refocus at least some of this growing energy into attacking not only With a little help, and a little imagination, we can change the pathologies of aging, but their underlying causes . that, too . 1: Transcript at http://articles.washingtonpost.com/2013-02-12/politics/37059380_1_applause-task-free-enterprise 2: Deloitte’s full report at http://www.deloitte.com/assets/Dcom-UnitedStates/Local%20Assets/Documents/us_dchs_2012_hidden_costs112712.pdf 3: From the WHO at http://www.who.int/mediacentre/factsheets/fs317/en/index.html -- full report available at http://www.who.int/nmh/publications/ncd_report_full_en.pdf 4: http://www.healthspancampaign.org/media-center/press-release/new-healthspan-campaign/ 5: SRF’s animation at http://sens.org/research 6: Information on SRF’s research at http://sens.org/research Research Summary intramural projects Lysosomal Aggregates SENS Research Foundation Research Center, Identifying enzymes in other life forms that can degrade Mountain View CA such wastes, and modifying these enzymes so they can be delivered to — and function in — our own lysosomes, Researchers: Gouri Yogalingam, Ghezal Beliakoff, Maximus Peto would restore cellular function and prevent or reverse these diseases . Cells are equipped with “incinerators” called lysosomes, where they send damaged or unwanted material for destruc- At the SENS Research Foundation Research Center (SRF- tion . But some cellular wastes are so chemically snarled that RC), our Lysosomal Aggregates team is working to efficiently even the lysosome is unable to shred them . With no way to deliver promising A2E-degrading enzymes identified in our eliminate these compounds, the cellular garbage simply earlier research into the lysosome of cells . One in particular builds up over time, progressively interfering with cell function . (SENS20) has demonstrated tremendous efficacy in degrading A2E not only in vitro but in A2E-loaded RPE cells . The disabling of specific cell types by their characteristic waste products drives numerous age-related diseases . For In 2013, the team will put a recombinant form of SENS20 to instance, age-related macular degeneration (AMD) — a the test, assessing its ability to degrade A2E in vitro and in major cause of blindness — is believed to be primarily RPE cells, and verifying that it is not toxic to the cell . caused by the accumulation of the waste A2E in the retinal pigment epithelial (RPE) cells of the eye . Synthesis and Uptake into Lysosomal uptake analysis purification of A2E RPE cells after two days of recovery A2E Anti-SENS20 MERGE 1600 1400 1200 1000 800 A2E Control (arbitrary units) 600 400 200 0 A2E A2E + SENS20 A2E + 3 ug/ml SENS20 Efficacy of SENS20 enzyme in degrading A2E in vitro Efficacy of SENS20 enzyme in degrading A2E in vivo Mitochondrial Mutations SENS Research Foundation Research Center, SRF-RC scientists are now working to master and refine a Mountain View CA superior method for accomplishing this goal . Our team has taken four cell lines from patients suffering from severe Researchers: Matthew O'Connor, Amutha Boominathan, diseases caused by inherited mitochondrial mutations and Jayanthi Vengalam made stable lines that express their improved mitochondrial gene constructs . They have begun collecting data confirming Our cells’ energy-producing mitochondria are at constant the targeting of gene transcripts and proteins to their risk of major mutations in their internal genes, because they mitochondrial locations, and the functional activity of the are housed close to where the mitochondria produce both mitochondrial energy system, in such re-engineered cells . cellular energy and the toxic byproducts of its generation . The Research Center’s Mitochondrial Mutations team is ATP Synthase particles working to engineer “backup copies” of vulnerable mito- Intermembrane space Matrix Ribosome chondrial genes, located in the safer location of the cell’s Cristae Unk RNA Granules binding mts 3'utr nucleus . This would let mitochondria keep producing energy protein normally, even after mitochondrial mutations have occurred . Inner membrane Outer membrane Cytoplasmic DNA Ribosome ETC Nuclear recoded mito gene Co-Translational Import Cancerous Cells SENS Research Foundation Research Center, to disrupt the system, opening up the power to strongly Mountain View CA suppress cancer . Researchers: Haroldo Silva, David Halvorsen, Kelsey Moody Our team is screening several cancer cell lines, looking for cells that display ALT behavior, in order to test whether they Cancer is a disease of unlimited cellular division . Healthy are exploiting specific candidate ALT genes . The most effec- cells have a built-in limit on the number of times they can tive way to identify such cells is by the extrachromosomal divide: with each division a stretch of DNA called the C-rich circular telomeric DNA (C-circles) that they generate . telomere progressively shortens, until it becomes so short that it prevents the cell from dividing or kills it outright . To Our researchers have recently developed an innovative bypass this limit, would-be cancer cells must exploit one version of the standard, radioisotope C-circle assay that of two escape systems . The most common method is to instead uses a non-radioactive digoxigenin (DIG)-labeled activate the gene for an enzyme called telomerase, which probe, and are also working to establish new protocols for re-lengthens shortened telomeres . The other, less common ALT-associated PML nuclear bodies, another key marker of approach is to activate a poorly-understood system known ALT activity . Establishing these two assays is a critical step as alternative lengthening of telomeres (ALT) . The goal towards deciphering the molecular mechanisms behind of the SRF-RC’s Cancerous Cells project is to identify ALT, developing novel diagnostics, and finding ways to the mechanisms of the latter and to use this knowledge shut ALT cancers down . Research Summary extramural projects Extracellular Matrix Stiffening Yale University, New Haven CT, and SENS Research center will initiate work on new agents to cleave apart Foundation Laboratory, Institute of Biotechnology, crosslinked proteins, restoring youthful elasticity and University of Cambridge, Cambridge UK buffering capacity to arteries . The specific molecular target will be glucosepane, the main crosslink that accumulates Researchers: David Spiegel (Yale); Chris