The Basics of Biogerontology
Total Page:16
File Type:pdf, Size:1020Kb
Load more
Recommended publications
-
The Ageing Haematopoietic Stem Cell Compartment
REVIEWS The ageing haematopoietic stem cell compartment Hartmut Geiger1,2, Gerald de Haan3 and M. Carolina Florian1 Abstract | Stem cell ageing underlies the ageing of tissues, especially those with a high cellular turnover. There is growing evidence that the ageing of the immune system is initiated at the very top of the haematopoietic hierarchy and that the ageing of haematopoietic stem cells (HSCs) directly contributes to changes in the immune system, referred to as immunosenescence. In this Review, we summarize the phenotypes of ageing HSCs and discuss how the cell-intrinsic and cell-extrinsic mechanisms of HSC ageing might promote immunosenescence. Stem cell ageing has long been considered to be irreversible. However, recent findings indicate that several molecular pathways could be targeted to rejuvenate HSCs and thus to reverse some aspects of immunosenescence. HSC niche The current demographic shift towards an ageing popu- The innate immune system is also affected by ageing. A specialized lation is an unprecedented global phenomenon that has Although an increase in the number of myeloid precur- microenvironment that profound implications. Ageing is associated with tissue sors has been described in the bone marrow of elderly interacts with haematopoietic attrition and an increased incidence of many types of can- people, the oxidative burst and the phagocytic capacity of stem cells (HSCs) to regulate cers, including both myeloid and lymphoid leukaemias, and both macrophages and neutrophils are decreased in these their fate. other haematopoietic cell malignancies1,2. Thus, we need individuals12,13. Moreover, the levels of soluble immune to understand the molecular and cellular mechanisms of mediators are altered with ageing. -
Biogerontology: a Novel Tool to Stay Healthy in Old Age
MoPAct Policy Brief: 5 Biogerontology: a novel tool to stay healthy in old age Policy priority Healthy lifestyle interventions in particular regarding nutrition and vaccination need to be implemented early in life with a lifecourse perspective. Summary: Key findings: • Accumulating evidence from experimental studies shows that aging is not inevitably linked with the development of chronic diseases. • Only 20-25% of healthy life expectancy (HLE) is predetermined by genes; lifestyle and environment play a major role. • Age-associated accumulation of molecular and cellular damage can be prevented or greatly delayed by lifestyle interventions e.g. dietary manipulations. • Classical strategies (e.g. nutrition, exercise, vaccination) require broad communication to public. • Novel strategies (e.g. dietary interventions, novel drugs, stem cells) need successful translation from the understanding of molecular mechanism to animal models to clinic. • To be successful interventions need to be started early Figure 1. Strategies to increase HLE. (1) Classical interventions include nutrition, exercise, vaccination, no smoking/alcohol/drugs. (2) Novel interventions include in life with a life-course perspective. dietary interventions, clearance of senescent and damaged cells, mitohormetics, stem cells, drugs against inflammation, rejuvenation factors from blood, telomeres, Background: epigenetic drugs, chaperons and proteolytic systems (novel interventions adapted from López-Otín et al., Cell 2013). Population aging is progressing fast in all developed countries. Aging is associated with the development of multiple serious chronic illnesses, including type 2 diabetes, hypertension, heart Prevention disease, stroke, cancer, cognitive impairment and increased Prevention prior to the development of age-associated diseases morbidity and mortality from infectious diseases. As people is key for successful aging. -
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. -
Disruptive Chemicals, Senescence and Immortality
Disruptive chemicals, senescence and immortality Carnero, A., Blanco-Aparicio, C., Kondoh, H., Lleonart, M. E., Martinez-Leal, J. F., Mondello, C., ... & Yasaei, H. (2015). Disruptive chemicals, senescence and immortality. Carcinogenesis, 36(Suppl 1), S19-S37. doi:10.1093/carcin/bgv029 10.1093/carcin/bgv029 Oxford University Press Version of Record http://cdss.library.oregonstate.edu/sa-termsofuse Carcinogenesis, 2015, Vol. 36, Supplement 1, S19–S37 doi:10.1093/carcin/bgv029 Review review Disruptive chemicals, senescence and immortality Amancio Carnero*, Carmen Blanco-Aparicio1, Hiroshi Kondoh2, Matilde E. Lleonart3, Juan Fernando Martinez-Leal4, Chiara Mondello5, A.Ivana Scovassi5, William H.Bisson6, Amedeo Amedei7, Rabindra Roy8, Jordan Woodrick8, Annamaria Colacci9, Monica Vaccari9, Jayadev Raju10, Fahd Al-Mulla11, Rabeah Al- Downloaded from Temaimi11, Hosni K. Salem12, Lorenzo Memeo13, Stefano Forte13, Neetu Singh14, Roslida A. Hamid15, Elizabeth P. Ryan16, Dustin G. Brown16, John Pierce Wise Sr17, Sandra S.Wise17 and Hemad Yasaei18 http://carcin.oxfordjournals.org/ Instituto de Biomedicina de Sevilla (IBIS/CSIC/HUVR/Univ. Sevilla), Oncohematology and Genetics Department, Avda Manuel siurot sn, 41013 Sevilla, Spain, 1Spanish National Cancer Research Center, Experimental Therapuetics Department, Melchor Fernandez Almagro, 3, 28029 Madrid, Spain, 2Department of Geriatric Medicine, Kyoto University Hospital, 54 Kawaharacho, Shogoin, Sakyo-ku Kyoto 606-8507, Japan, 3Institut De Recerca Hospital Vall D’Hebron, Passeig Vall d’Hebron, 119–129, -
The Emergence of Senescent Surface Biomarkers As Senotherapeutic Targets
cells Review The Emergence of Senescent Surface Biomarkers as Senotherapeutic Targets Martina Rossi and Kotb Abdelmohsen * Laboratory of Genetics and Genomics, RNA Regulation Section, National Institute on Aging Intramural Research Program, National Institutes of Health, 251 Bayview Blvd., Baltimore, MD 21224, USA; [email protected] * Correspondence: [email protected] Abstract: Senescence is linked to a wide range of age-associated diseases and physiological declines. Thus, senotherapeutics are emerging to suppress the detrimental effects of senescence either by senomorphics or senolytics. Senomorphics suppress the traits associated with senescence phenotypes, while senolytics aim to clear senescent cells by suppressing their survival and enhancing the apoptotic pathways. The main goal of these approaches is to suppress the proinflammatory senescence- associated secretory phenotype (SASP) and to promote the immune recognition and elimination of senescent cells. One increasingly attractive approach is the targeting of molecules or proteins specifically present on the surface of senescent cells. These proteins may play roles in the maintenance and survival of senescent cells and hence can be targeted for senolysis. In this review, we summarize the recent knowledge regarding senolysis with a focus on novel surface biomarkers of cellular senescence and discuss their emergence as senotherapeutic targets. Keywords: senescence; surface proteins; surfaceome; senolytics; senolysis; senostatic; senescent cell clearance; senotherapeutics; senotherapy Citation: Rossi, M.; Abdelmohsen, K. The Emergence of Senescent Surface Biomarkers as Senotherapeutic Targets. Cells 2021, 10, 1740. 1. Introduction https://doi.org/10.3390/cells Cellular senescence is a phenotype associated with limited replicative capacity and 10071740 irreversible growth arrest of primary cells first described by Leonard Hayflick in the early 1960s [1]. -
Does Senescence Promote Fitness in Caenorhabditis Elegans by Causing Death?
Institute of Healthy Ageing Preprint 1st Nov 2018 Essay Does senescence promote fitness in Caenorhabditis elegans by causing death? Jennifer N. Lohr1, Evgeniy R. Galimov1 and David Gems* Institute of Healthy Ageing, and Research Department of Genetics, Evolution and Environment, University College London, London WC1E 6BT, UK. 1These authors contributed equally. ∗ Corresponding author. E-mail address: [email protected] (D. Gems). 1 Institute of Healthy Ageing Preprint 1st Nov 2018 Abstract A widely appreciated conclusion from evolutionary theory is that senescence (aging) is of no adaptive value to the individual that it afflicts. Yet studies of C. elegans and S. cerevisiae are increasingly revealing the presence of processes which actively cause senescence and death, leading some biogerontologists to wonder about the established theory. Here we argue that programmed death that increases fitness could occur in C. elegans and S. cerevisiae, and that this is consistent with the classic evolutionary theory of aging. This is because of the special conditions under which these organisms have evolved, particularly the existence of clonal populations with limited dispersal and, in the case of C. elegans, the brevity of the reproductive period caused by protandry. Under these conditions, death-promoting mechanisms could promote worm fitness by enhancing inclusive fitness, or worm colony fitness through group selection. Such altruistic, adaptive death is not expected to evolve in organisms with outbred, dispersed populations. The plausibility of adaptive death in C. elegans is supported by computer modelling studies, and new knowledge about the ecology of this species. To support these arguments we also review the biology of adaptive death, and distinguish three forms: consumer sacrifice, biomass sacrifice and defensive sacrifice. -
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. -
Shared Ageing Research Models (Sharm): a New Facility to Support Ageing Research
Biogerontology (2013) 14:789–794 DOI 10.1007/s10522-013-9457-0 METHOD Shared Ageing Research Models (ShARM): a new facility to support ageing research Adele L. Duran • Paul Potter • Sara Wells • Tom Kirkwood • Thomas von Zglinicki • Anne McArdle • Cheryl Scudamore • Qing-Jun Meng • Gerald de Haan • Anne Corcoran • Ilaria Bellantuono Received: 5 July 2013 / Accepted: 16 August 2013 / Published online: 2 October 2013 Ó The Author(s) 2013. This article is published with open access at Springerlink.com Abstract In order to manage the rise in life expec- Wellcome Trust, open to all investigators. It collects, tancy and the concomitant increased occurrence of stores and distributes flash frozen tissues from aged age-related diseases, research into ageing has become murine models through its biorepository and provides a strategic priority. Mouse models are commonly a database of live ageing mouse colonies available in utilised as they share high homology with humans and the UK and abroad. It also has an online environment show many similar signs and diseases of ageing. (MICEspace) for collation and analysis of data from However, the time and cost needed to rear aged communal models and discussion boards on subjects cohorts can limit research opportunities. Sharing of such as the welfare of ageing animals and common resources can provide an ethically and economically endpoints for intervention studies. Since launching in superior framework to overcome some of these issues July 2012, thanks to the generosity of researchers in but requires dedicated infrastructure. Shared Ageing UK and Europe, ShARM has collected more than Research Models (ShARM) (www.ShARMUK.org) 2,500 tissues and has in excess of 2,000 mice regis- is a new, not-for-profit organisation funded by tered in live ageing colonies. -
Viewer Comments
Article Oxylipin biosynthesis reinforces cellular senescence and allows detection of senolysis Graphical abstract Authors Christopher D. Wiley, Rishi Sharma, Sonnet S. Davis, ..., Marco Demaria, Arvind Ramanathan, Judith Campisi Correspondence [email protected] (C.D.W.), [email protected] (A.R.), [email protected] (J.C.) In brief Senolytics, transgenic, and pharmacological interventions that selectively kill senescent cells are currently in clinical trials aiming to treat age-related degenerative pathologies. Here, Wiley et al. discover that senescent cells produce multiple signaling lipids known as oxylipins. One oxylipin, dihomo-15d-PGJ2, promotes features of senescence by activating RAS and is released from cells during senolysis, serving as the first biomarker of the Highlights process in culture and in vivo. d Senescent cells make several oxylipins, dihomo- prostaglandins, and leukotrienes d Dihomo-15d-PGJ2 is intracellular during senescence and released during senolysis d Dihomo-15d-PGJ2 activates RAS, promoting senescence and the SASP d Positive feedback between prostaglandins, RAS, and p53 maintains senescence Wiley et al., 2021, Cell Metabolism 33, 1–13 June 1, 2021 ª 2021 Published by Elsevier Inc. https://doi.org/10.1016/j.cmet.2021.03.008 ll Please cite this article in press as: Wiley et al., Oxylipin biosynthesis reinforces cellular senescence and allows detection of senolysis, Cell Metabolism (2021), https://doi.org/10.1016/j.cmet.2021.03.008 ll Article Oxylipin biosynthesis reinforces cellular senescence and allows detection of senolysis Christopher D. Wiley,1,2,* Rishi Sharma,1 Sonnet S. Davis,1 Jose Alberto Lopez-Dominguez,1 Kylie P. Mitchell,1 Samantha Wiley,1 Fatouma Alimirah,1 Dong Eun Kim,1 Therese Payne,1 Andrew Rosko,1 Eliezer Aimontche,1 Sharvari M. -
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 -
HCB 524 — Transhumanism
HCB 524 Special Topic in Bioethics Fall Semester, 2019. Tuesdays 6-8:30pm. Instructor of Record: Adam Sepe, MA, MLS(ASCP)cm [email protected] Course Description: Transhumanism and [Human?] Dignity. Throughout human history — and prehistory for that matter — technological advancement has drastically altered every aspect of human life. Most of us will say that many advents — such as cooking and the wheel — have been largely, if not entirely, beneficial. Would we say the same of all technology? Surely each of us can list technologies that have, in the very least, some considerable downsides. So while history and experience can tell us that some technologies are beneficial and that some other technologies are harmful, how can we know what kind of impact future technology will have? For now we can’t, and so all we can do is try, to the best of our ability, to imagine such futures and develop our technology with these considerations in mind. ‘Transhumanism’ refers a diverse collection of ideas that have one at least thing in common: through future technology, humanity will be fundamentally altered to an unprecedented degree. Some even believe there will come a time when, through our own action, the word ‘human’ will be obsolete; that we will be succeeded by entities (or an entity) for which ‘human’ does not apply. Most people who identify as transhumanists are, to varying degrees, proponents of such technology. They are in favor of such alterations and they argue that these will be beneficial. In this course, we will take a critical look at transhumanist claims.