DOCSLIB.ORG

SENS Research Foundation Annual Report 2012

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
SENS Research Foundation Annual Report 2012 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 Bypass surgery is obsolete, and heart attacks and stroke no longer occur .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
Load more

Recommended publications
  • Mixing Old and Young: Enhancing Rejuvenation and Accelerating Aging
    Mixing old and young: enhancing rejuvenation and accelerating aging Ashley Lau, … , James L. Kirkland, Stefan G. Tullius J Clin Invest. 2019;129(1):4-11. https://doi.org/10.1172/JCI123946. Review Donor age and recipient age are factors that influence transplantation outcomes. Aside from age-associated differences in intrinsic graft function and alloimmune responses, the ability of young and old cells to exert either rejuvenating or aging effects extrinsically may also apply to the transplantation of hematopoietic stem cells or solid organ transplants. While the potential for rejuvenation mediated by the transfer of youthful cells is currently being explored for therapeutic applications, aspects that relate to accelerating aging are no less clinically significant. Those effects may be particularly relevant in transplantation with an age discrepancy between donor and recipient. Here, we review recent advances in understanding the mechanisms by which young and old cells modify their environments to promote rejuvenation- or aging-associated phenotypes. We discuss their relevance to clinical transplantation and highlight potential opportunities for therapeutic intervention. Find the latest version: https://jci.me/123946/pdf REVIEW The Journal of Clinical Investigation Mixing old and young: enhancing rejuvenation and accelerating aging Ashley Lau,1 Brian K. Kennedy,2,3,4,5 James L. Kirkland,6 and Stefan G. Tullius1 1Division of Transplant Surgery, Department of Surgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA. 2Departments of Biochemistry and Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. 3Singapore Institute for Clinical Sciences, Singapore. 4Agency for Science, Technology and Research (A*STAR), Singapore.
    [Show full text]
  • Who Wants to Live Forever? Reader’S Digest
    HEALTH Who Wantsto Live Forever? As a species, we humans appear to be the undisputed masters of our planet. Moreover, since Yuri Gagarin’s inaugural space flight in 1961, we can even leave the confines of Earth to travel in space. Yet, we have one Achilles’ heel—we’re mortal BY CHRIS MENON 1234567890 1234567890 36 BRAIN LIGHT/ALAMY STOCK PHOTO WHO WANTS TO LIVE FOREVER? READEr’s DIGEST T 122 YEARS, THE MAXIMUM HUMAN LIFESPAN lags well behind some species of giant tortoise (188 years), Greenland shark (400 years) and the record set by the lowly Icelandic clam (507 years). Even those relatively few humans who do manage to make it past 100—some 14,570 people in the UK in 2015—are invariably bedeviled byA poor health. Recently, efforts to extend the healthy of Amazon, has similarly invested human lifespan have achieved much in Unity Biotechnology, which aims publicity following the backing of “to design therapeutics that prevent, visionary, super-rich Silicon Valley halt, or reverse diseases of ageing”. tech entrepreneurs. In 2013, Google’s Unity intends to develop a new founders created a subsidiary class of therapies called “senolytic company called Calico (short for medicines”, designed to selectively the California Life Company), eliminate senescent cells. Senescent Billionaire researchers, which promptly hired a team of top cells accumulate with age and, Some believe that death, Arthur Levinson, Jeff technologies that scientists and now has more than unlike normal cells, they secrete like any disease, can be Bezos and Elon Musk the SENS Research £1bn in the bank to fund its work.
    [Show full text]
  • Vascular Tissue Challenge Official Rules Updated 2019-08-14
    Vascular Tissue Challenge Official Rules Updated 2019-08-14 SECTION 1: Executive Summary 2 SECTION 2: Definitions & Assumptions 3 SECTION 3: Evaluation Criteria 3 SECTION 4: Safety & Care 5 SECTION 5: Registration Requirements 5 SECTION 6: Judging 6 SECTION 7: Timeline 8 SECTION 8: Eligibility, Disqualification, & Appeal 9 SECTION 9: Awards 10 The Methuselah Foundation Vascular Tissue Challenge Rules Page 1 SECTION 1: EXECUTIVE SUMMARY Objectives Summary The Vascular Tissue Challenge (hereafter “Challenge”) is a $500,000 prize purse to be divided among the first three teams who can successfully create thick, human vascularized organ tissue in an in-vitro environment while maintaining metabolic functionality similar to their in vivo native cells throughout a 30 calendar day survival period. NASA’s objective for this Challenge is to produce technologies capable of creating viable thick (>1cm) metabolic tissues that can be used to advance research on human physiology, fundamental space biology, and medicine taking place both on the Earth and the ISS National Laboratory. Specifically, technology innovations may enable the growth of de novo tissues and organs on orbit which may address the risks related to traumatic bodily injury, improve general crew health, and enhance crew performance on future, long-duration missions. Evaluation Criteria Summary Produce an in vitro vascularized tissue that is > 1 centimeter in thickness in all dimensions at the launch of the trial and maintains >85% survival of the required parenchymal cells throughout a 30 calendar day period. Tissues must provide adequate blood perfusion without uncontrolled leakage into the bulk tissue to maintain metabolic functionality similar to their in vivo native cells.
    [Show full text]
  • Cellular Senescence Promotes Skin Carcinogenesis Through P38mapk and P44/P42mapk Signaling
    Author Manuscript Published OnlineFirst on July 8, 2020; DOI: 10.1158/0008-5472.CAN-20-0108 Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Cellular senescence promotes skin carcinogenesis through p38MAPK and p44/p42 MAPK signaling Fatouma Alimirah1, Tanya Pulido1, Alexis Valdovinos1, Sena Alptekin1,2, Emily Chang1, Elijah Jones1, Diego A. Diaz1, Jose Flores1, Michael C. Velarde1,3, Marco Demaria1,4, Albert R. Davalos1, Christopher D. Wiley1, Chandani Limbad1, Pierre-Yves Desprez1, and Judith Campisi1,5* 1Buck Institute for Research on Aging, Novato, CA 94945, USA 2Dokuz Eylul University School of Medicine, Izmir 35340, Turkey 3Institute of Biology, University of the Philippines Diliman, College of Science, Quezon City 1101, Philippines 4European Research Institute for the Biology of Ageing, University Medical Center Groningen, Groningen, the Netherlands 5Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA *Lead Contact: Judith Campisi, Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945, USA; Email: [email protected] or [email protected]. Telephone: 1-415-209-2066; Fax: 1-415-493-3640 Running title: Senescence and skin carcinogenesis Key words: doxorubicin, senescence-associated secretory phenotype, squamous cell carcinoma, microenvironment, inflammation, transgenic mice, tumorspheres Conflict of Interests JC is a co-founder of Unity Biotechnology and MD owns equity in Unity Biotechnology. All other authors declare no competing financial interests. Downloaded from cancerres.aacrjournals.org on September 25, 2021. © 2020 American Association for Cancer Research. Author Manuscript Published OnlineFirst on July 8, 2020; DOI: 10.1158/0008-5472.CAN-20-0108 Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited.
    [Show full text]
  • From Here to Immortality: Anti-Aging Medicine
    FromFrom HereHere toto Immortality:Immortaalitty: AAnti-AgingAnnntti-AAgging MMedicineedicine Anti-aging medicine is a $5 billion industry. Despite its critics, researchers are discovering that inter ventions designed to turn back time may prove to be more science than fiction. By Trudie Mitschang 14 BioSupply Trends Quarterly • October 2013 he symptoms are disturbing. Weight gain, muscle Shifting Attitudes Fuel a Booming Industry aches, fatigue and joint stiffness. Some experience The notion that aging requires treatment is based on a belief Thear ing loss and diminished eyesight. In time, both that becoming old is both undesirable and unattractive. In the memory and libido will lapse, while sagging skin and inconti - last several decades, aging has become synonymous with nence may also become problematic. It is a malady that begins dete rioration, while youth is increasingly revered and in one’s late 40 s, and currently 100 percent of baby boomers admired. Anti-aging medicine is a relatively new but thriving suffer from it. No one is immune and left untreated ; it always field driven by a baby- boomer generation fighting to preserve leads to death. A frightening new disease, virus or plague? No , its “forever young” façade. According to the market research it’s simply a fact of life , and it’s called aging. firm Global Industry Analysts, the boomer-fueled consumer The mythical fountain of youth has long been the subject of base will push the U.S. market for anti-aging products from folklore, and although it is both natural and inevitable, human about $80 billion now to more than $114 billion by 2015.
    [Show full text]
  • SENS-Research-Foundation-2019
    by the year 2050, cardiovascular an estimated 25-30 the american 85 percent of adults disease years and older age 85 or older remains the most population will suffer from common cause of 2 1 2 dementia. death in older adults. triple. THE CLOCK IS TICKING. By 2030, annual direct The estimated cost of medical costs associated dementia worldwide was 62% of Americans with cardiovascular $818 billion diseases in the united over age 65 have in 2015 and is states are expected to more than one expected to grow to rise to more than chronic condition.1 3 $2 trillion $818 billion. by 2030.1 References: (1) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5732407/, (2) https://www.who.int/ageing/publications/global_health.pdf, (3) https://www.cdcfoundation.org/pr/2015/heart-disease-and-stroke-cost-america-nearly-1-billion-day-medical-costs-lost-productivity sens research foundation board of directors Barbara Logan Kevin Perrott Bill Liao Chairperson Treasurer Secretary Michael Boocher Kevin Dewalt James O’Neill Jonathan Cain Michael Kope Frank Schuler 02 CONTENTS 2019 Annual Report 04 Letter From The CEO 06 Outreach & Fundraising 08 Finances 09 Donors erin ashford photography 14 Education 26 Investments 20 Conferences & Events 30 Research Advisory Board 23 Speaking Engagements 31 10 Years Of Research 24 Alliance 32 MitoSENS 34 LysoSENS 35 Extramural Research 38 Publications 39 Ways to Donate cover Photo (c) Mikhail Leonov - stock.adobe.com special 10th anniversary edition 03 FROM THE CEO It’s early 2009, and it’s very late at night. Aubrey, Jeff, Sarah, Kevin, and Mike are sitting around a large table covered in papers and half-empty food containers.
    [Show full text]
  • 1 of 16 SAA8-2032718 NONREIMBURSABLE SPACE ACT AGREEMENT BETWEEN the NATIONAL AERONAUTICS and SPACE ADMINISTRATION GEORGE
    NONREIMBURSABLE SPACE ACT AGREEMENT BETWEEN THE NATIONAL AERONAUTICS AND SPACE ADMINISTRATION GEORGE C. MARSHALL SPACE FLIGHT CENTER AND METHUSELAH FOUNDATION FOR THE CENTENNIAL CHALLENGES LUNAR NUTRITION CHALLENGE ARTICLE 1. AUTHORITY AND PARTIES In accordance with the National Aeronautics and Space Act (51 U.S.C. § 20113(e)), this Agreement is entered into by the National Aeronautics and Space Administration George C. Marshall Space Flight Center, located at Marshall Space Flight Center, AL 35812 (hereinafter referred to as "NASA" or "NASA MSFC") and Methuselah Foundation located at 8021 Flint Street, Springfield , VA 22153-2438 (hereinafter referred to as "Partner" or "MF"). NASA and Partner may be individually referred to as a "Party" and collectively referred to as the "Parties." ARTICLE 2. PURPOSE This Agreement shall be for the purpose of conducting the Lunar Nutrition Challenge for NASA Centennial Challenges program. This Challenge seeks to identify and foster the development and demonstration of novel technologies and/or approaches for food production for long duration space exploration missions. As part of the initial human presence on the Moon by 2024 and a sustainable human presence on the Moon by 2028, NASA's missions will become longer in duration and require sustainable systems that meet lunar crews' needs. This Challenge is focused on how to provide crew members with: • a viable food system for long duration missions • an approach that meets crew members' daily nutritional needs with limited resources • a palatable diet with limited or no dependency on Earth resupplies; and potentially a • ‘harvest' that provides a variety of food choices For the term of this Agreement, the Challenge will be developed and conducted by MF to foster these novel approaches to food production.
    [Show full text]
  • 5 EVENTS in ONE: Head Real World Evidence and Big Data Solutions Novartis, Switzerland
    FIFTH ANNUAL - LIFE SCIENCE R&D DATA INTELLIGENCE LEADERS FORUM Basel, Switzerland January 23-24th, 2018 Optional Workshop 22nd, January Hear keynote presentations from the experts: Etzard Stolte Global Head Knowledge Management Roche, Switzerland Abhimanyu Verma 5 EVENTS IN ONE: Head Real World Evidence and Big Data Solutions Novartis, Switzerland Day 1: Torsten Niederdraenk Head of Technology Center Strategic Developments in R&D Big Siemens Healthcare, Germany Data Catherine Brownstein Scientific Director Day 2 (am): Stream 1 Manton Center for Orphan Disease Research Boston Children’s Hospital, USA Discovery & Omics Data Excellence Navin Ramachandran Radiology Consultant Day 2 (am): Stream 2 University College London Hospitals NHS Foundation Trust, Healthcare specialist in distributed ledgers and IoT Clinical & Patient Level Data IOTA Foundation, UK Excellence Marie-Claire Peakman Executive Director, Head Hit Discovery & Lead Profiling, Medicine Design Day 2 (pm): Stream A Pfizer, USA R&D IT & Bioinformatics Alex Zhavoronkov Co-founder, Insilico Medicine, CSO Day 2 (pm): Stream B The Biogerontology Research Foundation, UK Ivana Schnur Digital Health Collaborations Co-founder, CMO Sense.ly, USA Pre-Event Workshop: Jan 22nd Paul Wicks Artificial Intelligence for Drug Vice President of Innovation PatientsLikeMe, UK Discovery: Workshop for Senior Jazz Panchoo Global Strategy Head, VP, Digital Platforms Executives Ascensia Diabetes Care, Switzerland This Event is Certified for Continuing Professional Development with more than 30 presentations
    [Show full text]
  • Read Our New Annual Report
    The seeds of a concept. The roots of an idea. The potential of a world free of age-related disease. Photo: Sherry Loeser Photography SENS Research Foundation Board of Directors Barbara Logan, Chair Bill Liao, Secretary Kevin Perrott, Treasurer Michael Boocher Jonathan Cain Kevin Dewalt Michael Kope Jim O’Neill Frank Schüler Sherry Loeser Photography 2 Contents CEO Letter (Jim O’Neill) 4 Finances 5 Donors 6 - 7 Fundraising & Conferences 8 - 9 Around the World with Aubrey de Grey 10 Outreach 11 Founding CEO Tribute & Underdog Pharmaceuticals 12 - 13 Investments 14 Welcome New Team Members 15 Education 16 - 17 Publications & Research Advisory Board 18 Research Summaries 19 - 22 Ways to Donate 23 The SRF Team Front row: Anne Corwin (Engineer/Editor), Amutha Boominathan (MitoSENS Group Lead), Alexandra Stolzing (VP of Research), Aubrey de Grey (Chief Science Officer), Jim O’Neill (CEO), Bhavna Dixit (Research Associate). Center row: Caitlin Lewis (Research Associate), Lisa Fabiny-Kiser (VP of Operations), Gary Abramson (Graphics), Maria Entraigues-Abramson (Global Outreach Coordinator), Jessica Lubke (Administrative Assistant). Back row: Tesfahun Dessale Admasu (Research Fellow), Amit Sharma (ImmunoSENS Group Lead), Michael Rae (Science Writer), Kelly Protzman (Executive Assistant). Not Pictured: Greg Chin (Director, SRF Education), Ben Zealley (Website/Research Assistant/ Deputy Editor) Photo: Sherry Loeser Photography, 2019 3 From the CEO At our 2013 conference at Queens College, Cambridge, I closed my talk by saying, “We should not rest until we make aging an absurdity.” We are now in a very different place. After a lot of patient explanation, publication of scientific results, conferences, and time, our community persuaded enough scientists of the feasibility of the damage repair approach to move SENS and SENS Research Foundation from the fringes of scientific respectability to the vanguard of a mainstream community of scientists developing medical therapies to tackle human aging.
    [Show full text]
  • Age-Dependent Deterioration of Nuclear Pore Assembly in Mitotic
    RESEARCH ARTICLE Age-dependent deterioration of nuclear pore assembly in mitotic cells decreases transport dynamics Irina L Rempel1, Matthew M Crane2, David J Thaller3, Ankur Mishra4, Daniel PM Jansen1, Georges Janssens1, Petra Popken1, Arman Aks¸it1, Matt Kaeberlein2, Erik van der Giessen4, Anton Steen1, Patrick R Onck4, C Patrick Lusk3, Liesbeth M Veenhoff1* 1European Research Institute for the Biology of Ageing (ERIBA), University of Groningen, University Medical Center Groningen, Groningen, Netherlands; 2Department of Pathology, University of Washington, Seattle, United States; 3Department of Cell Biology, Yale School of Medicine, New Haven, United States; 4Zernike Institute for Advanced Materials, University of Groningen, Groningen, Netherlands Abstract Nuclear transport is facilitated by the Nuclear Pore Complex (NPC) and is essential for life in eukaryotes. The NPC is a long-lived and exceptionally large structure. We asked whether NPC quality control is compromised in aging mitotic cells. Our images of single yeast cells during aging, show that the abundance of several NPC components and NPC assembly factors decreases. Additionally, the single-cell life histories reveal that cells that better maintain those components are longer lived. The presence of herniations at the nuclear envelope of aged cells suggests that misassembled NPCs are accumulated in aged cells. Aged cells show decreased dynamics of transcription factor shuttling and increased nuclear compartmentalization. These functional changes are likely caused by the presence
    [Show full text]
  • Longevity and Generosity. the Death of Death. July 2018. N° 112
    Longevity and generosity. The death of death. July 2018. N° 112. Some people say, “Oh, you shouldn’t do enhancement” but the thing is we do enhancement all the time — to some extent, all aging reversal is enhancement. ​ ​ ​ ​ Vaccines are enhancement… I think I’m just now getting up to speed after 63 years of education. Aging reversal is something that will buy me and many of my colleagues a lot more time to make many more contributions, so you might consider that a meta-level contribution, if we can pull that off. World-renowned ​ Harvard University biology researcher George Church (source). ​ ​ ​ ​ Theme of the month. How to contribute financially to research for a much longer healthy life Introduction If you have considerable financial means you can afford medical care more easily than less well-off citizens. But whether you are rich or not, with a good "genetic capital" or not, whatever your precautions and your anti-aging clinic visits, in the current state of knowledge your chances are low of living more than 100 years if you are a woman and beyond 95 years if you are of the weaker sex for longevity. And whatever happens, you will not live past 122 years for a ​ ​ woman et 116 years for a man. ​ ​ To go further will require complex and costly research. If informed citizens pay money to support this research, it will be positive in a direct way by funding the research. It will also be positive in that it will show the growing interest in these issues. What could you do about it? Moderate financial support If your financial means are limited or if you do not wish to make large donations, your action can still have an impact.
    [Show full text]
  • Transhumanism, Metaphysics, and the Posthuman God
    Journal of Medicine and Philosophy, 35: 700–720, 2010 doi:10.1093/jmp/jhq047 Advance Access publication on November 18, 2010 Transhumanism, Metaphysics, and the Posthuman God JEFFREY P. BISHOP* Saint Louis University, St. Louis, Missouri, USA *Address correspondence to: Jeffrey P. Bishop, MD, PhD, Albert Gnaegi Center for Health Care Ethics, Saint Louis University, 3545 Lafayette Avenure, Suite 527, St. Louis, MO 63104, USA. E-mail: [email protected] After describing Heidegger’s critique of metaphysics as ontotheol- ogy, I unpack the metaphysical assumptions of several transhu- manist philosophers. I claim that they deploy an ontology of power and that they also deploy a kind of theology, as Heidegger meant it. I also describe the way in which this metaphysics begets its own politics and ethics. In order to transcend the human condition, they must transgress the human. Keywords: Heidegger, metaphysics, ontology, ontotheology, technology, theology, transhumanism Everywhere we remain unfree and chained to technology, whether we passionately affirm or deny it. —Martin Heidegger I. INTRODUCTION Transhumanism is an intellectual and cultural movement, whose proponents declare themselves to be heirs of humanism and Enlightenment philosophy (Bostrom, 2005a, 203). Nick Bostrom defines transhumanism as: 1) The intellectual and cultural movement that affirms the possibility and desirability of fundamentally improving the human condition through applied reason, especially by developing and making widely available technologies to eliminate aging and to greatly enhance human intellectual, physical, and psychological capacities. 2) The study of the ramifications, promises, and potential dangers of technologies that will enable us to overcome fundamental human limitations, and the related study of the ethical matters involved in developing and using such technologies (Bostrom, 2003, 2).
    [Show full text]