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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. -
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. -
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. -
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 -
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). -
Dissecting Aging and Senescence—Current Concepts and Open Lessons
cells Review Dissecting Aging and Senescence—Current Concepts and Open Lessons 1,2, , 1,2, 1 1,2 Christian Schmeer * y , Alexandra Kretz y, Diane Wengerodt , Milan Stojiljkovic and Otto W. Witte 1,2 1 Hans-Berger Department of Neurology, Jena University Hospital, 07747 Jena, Thuringia, Germany; [email protected] (A.K.); [email protected] (D.W.); [email protected] (M.S.); [email protected] (O.W.W.) 2 Jena Center for Healthy Ageing, Jena University Hospital, 07747 Jena, Thuringia, Germany * Correspondence: [email protected] These authors have contributed equally. y Received: 2 October 2019; Accepted: 13 November 2019; Published: 15 November 2019 Abstract: In contrast to the programmed nature of development, it is still a matter of debate whether aging is an adaptive and regulated process, or merely a consequence arising from a stochastic accumulation of harmful events that culminate in a global state of reduced fitness, risk for disease acquisition, and death. Similarly unanswered are the questions of whether aging is reversible and can be turned into rejuvenation as well as how aging is distinguishable from and influenced by cellular senescence. With the discovery of beneficial aspects of cellular senescence and evidence of senescence being not limited to replicative cellular states, a redefinition of our comprehension of aging and senescence appears scientifically overdue. Here, we provide a factor-based comparison of current knowledge on aging and senescence, which we converge on four suggested concepts, thereby implementing the newly emerging cellular and molecular aspects of geroconversion and amitosenescence, and the signatures of a genetic state termed genosenium. -
Mechanisms and Rejuvenation Strategies for Aged Hematopoietic
Li et al. Journal of Hematology & Oncology (2020) 13:31 https://doi.org/10.1186/s13045-020-00864-8 REVIEW Open Access Mechanisms and rejuvenation strategies for aged hematopoietic stem cells Xia Li1,2,3†, Xiangjun Zeng1,2,3†, Yulin Xu1,2,3, Binsheng Wang1,2,3, Yanmin Zhao1,2,3, Xiaoyu Lai1,2,3, Pengxu Qian1,2,3 and He Huang1,2,3* Abstract Hematopoietic stem cell (HSC) aging, which is accompanied by reduced self-renewal ability, impaired homing, myeloid-biased differentiation, and other defects in hematopoietic reconstitution function, is a hot topic in stem cell research. Although the number of HSCs increases with age in both mice and humans, the increase cannot compensate for the defects of aged HSCs. Many studies have been performed from various perspectives to illustrate the potential mechanisms of HSC aging; however, the detailed molecular mechanisms remain unclear, blocking further exploration of aged HSC rejuvenation. To determine how aged HSC defects occur, we provide an overview of differences in the hallmarks, signaling pathways, and epigenetics of young and aged HSCs as well as of the bone marrow niche wherein HSCs reside. Notably, we summarize the very recent studies which dissect HSC aging at the single-cell level. Furthermore, we review the promising strategies for rejuvenating aged HSC functions. Considering that the incidence of many hematological malignancies is strongly associated with age, our HSC aging review delineates the association between functional changes and molecular mechanisms and may have significant clinical relevance. Keywords: Hematopoietic stem cells, Aging, Single-cell sequencing, Epigenetics, Rejuvenation Background in the clinic, donor age is carefully considered in HSC A key step in hematopoietic stem cell (HSC) aging re- transplantation, and young donors result in better sur- search was achieved in 1996, revealing that HSCs from vival after HSC transplantation [2–4]. -
SENS Research Foundation Annual Report 2015
S E N S R e s e a r c h F o u n d a t i o n has a unique mission: to ensure the development of cures which repair the underlying cellular and molecular damage of aging. This document, our 2 0 1 5 R e p o r t, demonstrates our commitment to delivering on the promise of that mission, and to meeting the challenges facing the rapidly emerging rejuvenation biotechnology field. Our research program delivers key proof-of-concept results. Our education program prepares the first generation of rejuvenation biotechnology professionals. Our outreach program widens and connects our communi. Our Rejuvenation Biotechnology conferences unite stakeholders from academic, industrial, political, regulatory and financial institutions. Together, we are transforming the way the world researches and treats age-related disease. i n t r o d u c t i o n 2 l e t t e r f r o m t h e C E O 3 c o m m u n i t y 4 o u t r e a c h 6 e d u c a t i o n 8 r e s e a r c h 1 0 f i n a n c e s 1 4 r e s e a r c h : p r o j e c t b y p r o j e c t 1 5 s u p p o r t i n g t h e f o u n d a t i o n 2 3 FOUNDATION BOARD OF LEADERSHIP DIRECTORS Mike Kope Barbara Logan Jonathan Cain Chief Executive Officer Board Chair Kevin Dewalt Kevin Perrott Dr. -
The End of Extrapolation by Dr Aubrey De Grey
Longevity in the 21st century: When medicine trumps extrapolation Aubrey D.N.D. de Grey, Ph.D. Chief Science Officer, SENS Research Foundation, USA VP New Technology Discovery, AgeX Therapeutics, USA Aubrey D.N.J. de Grey, Ph.D. Chief Science Officer, SENS Research Foundation VP New Technology Discovery, AgeX Therapeutics [email protected] [email protected] http://www.sens.org/ * Source: http://esa.un.org/wpp/unpp/panel_population.htm If historical rates continue, US healthcare spending will be 34% of GDP by 2040. Source: http://www.whitehouse. gov/administration/eop/ cea/TheEconomicCasef orHealthCareReform In 2010, the US spent $1.186 trillion on healthcare for people 65+ Source: http://www.deloitte.com/ assets/Dcom- UnitedStates/Local%20 Assets/Documents/us_ dchs_2012_hidden_cos ts112712.pdf Source: http://sambaker.com/econ/classes/nhe10/ Most infectious diseases have been easily prevented ▪ Sanitation ▪ Vaccines ▪ Antibiotics ▪ Carrier control Age-related diseases have not. Why not? presbycusis osteoporosis reduced light adaptation impaired pH maintenance osteoarthritis reduced ethanol metabolism reduced chemical clearance autoimmunity altered drug pharmacokinetics altered dermal immune cell residence and function greying hair somatopause aberrant allergic and irritant reactions presbyopia loss of cardiac adaptability loss of skin elasticity cataract incontinence impaired vitamin D synthesis glaucoma impaired wound healing reduced renal reserve temporal arteritis idiopathic axonal polyneuropathy renal cortex atrophy polymyalgia rheumatica -
SENS Research Foundation Annual Report 2014
sens research foundation foundation report august 2014 mission 2 leer from the CEO 3 outreach 4 research 8 education 14 finances 16 research: project by project 18 FOUNDATION BOARD OF LEADERSHIP DIRECTORS Mike Kope Barbara Logan Jonathan Cain Chief Executive Officer Board Chair Kevin Dewalt Kevin Perrott Aubrey de Grey Treasurer James O’Neill Chief Science Officer Bill Liao Mike Kope Secretary © 2014, SENS Research Foundation a: 110 Pioneer Way, Suite J / Mountain View, CA 94041 / USA p: 650.336.1780 f: 650.336.1781 www.sens.org All rights reserved. No part of this material may be reproduced without specific permission from SENS Research Foundation. SENS Research Foundation’s federal employer ID number is 94-3473864. Because SENS Research Foundation is a 501(c)(3) non-profit, your donation may be tax deductible. transforming the way the world researches and treats age-related disease We fund research at institutions around the world, and at our own Moun- tain View facility. Our research is integrated with wide-ranging outreach and education programs. Our goal is to see the emergence of an industry that will cure the diseases of aging, an industry based around what we call rejuvenation biotechnology. Many things go wrong with aging bodies, but at the root of them all is the burden of decades of unrepaired damage to the cellular and molecular structures that make up the functional units of our tissues. Faced with the diseases and disabilities caused by this damage, today’s medicine is too often reduced to crisis management in the emergency room, painfully harsh treatments for diseases such as cancer, or best efforts at palliative care. -
Life Extension Pseudoscience and the SENS Plan
Life Extension Pseudoscience and the SENS Plan Preston W. Estep III, Ph.D. President and CEO, Longenity Inc. Matt Kaeberlein, Ph.D. Department of Pathology University of Washington Pankaj Kapahi, Ph.D. Buck Institute for Age Research Brian K. Kennedy, Ph.D. Department of Biochemistry University of Washington Gordon J. Lithgow Ph.D. Buck Institute for Age Research George M. Martin, M.D. Department of Pathology University of Washington Simon Melov, Ph.D. Buck Institute for Age Research R. Wilson Powers III Department of Genome Sciences University of Washington Heidi A. Tissenbaum, Ph.D. Program in Gene Function and Expression Program in Molecular Medicine University of Massachusetts Medical School Abstract Recent scientific advances have taken gerontological research to challenging and exciting new frontiers, and have given many scientists increased confidence that human aging is to some degree controllable. We have been on the front lines of some of these developments and the speculative discussions they have engendered, and we are proud to be part of the increasingly productive biomedical effort to reduce the pathologies of aging, and age-associated diseases, to the greatest degree possible—and to extend healthy human life span to the greatest degree possible. In contrast to clearly justifiable speculations regarding future advances in human longevity a few have made claims that biological immortality is within reach. One, Aubrey de Grey, claims to have developed a “detailed plan to cure human aging” called Strategies for Engineered Negligible Senescence (SENS) [1, 2]. This is an extraordinary claim, and we believe that extraordinary claims require extraordinary evidentiary support. In supplementary material posted on the Technology Review web site we evaluate SENS in detail. -
Inflammation and Aging of Hematopoietic Stem Cells in Their
cells Review Inflammation and Aging of Hematopoietic Stem Cells in Their Niche Daozheng Yang 1 and Gerald de Haan 1,2,* 1 European Research Institute for the Biology of Ageing (ERIBA), University Medical Center Groningen, University of Groningen, 9713 AV Groningen, The Netherlands; [email protected] 2 Sanquin Research, Landsteiner Laboratory, Amsterdam UMC, 1006 AD Amsterdam, The Netherlands * Correspondence: [email protected] Abstract: Hematopoietic stem cells (HSCs) sustain the lifelong production of all blood cell lineages. The functioning of aged HSCs is impaired, including a declined repopulation capacity and myeloid and platelet-restricted differentiation. Both cell-intrinsic and microenvironmental extrinsic factors contribute to HSC aging. Recent studies highlight the emerging role of inflammation in contributing to HSC aging. In this review, we summarize the recent finding of age-associated changes of HSCs and the bone marrow niche in which they lodge, and discuss how inflammation may drive HSC aging. Keywords: hematopoietic stem cells; aging; niche; heterogeneity; inflammation 1. Age-Associated Changes in HSCs 1.1. The Functioning of Hematopoietic Stem Cells Declines with Age Multiple aging-associated hematopoietic features occur in both peripheral blood (PB) Citation: Yang, D.; de Haan, G. and bone marrow (BM). Aged mice display elevated platelet counts [1–3] and myeloid Inflammation and Aging of cells [4], with concomitant decreased red blood cells (RBC) [1,3] and haemoglobin (Hb) [1,3]. Hematopoietic Stem Cells in Their In aged BM, there is an increase in the frequency of committed megakaryocyte progenitors Niche. Cells 2021, 10, 1849. https:// (MkPs) [1,2,5,6] and granulocyte-monocyte progenitor (GMP) [2,6] and a decline in the doi.org/10.3390/cells10081849 frequency of common lymphoid progenitor (CLP) [6,7] and colony forming unit-erythroid (CFU-E) [2,6].