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Age Asymmetry SIGNED

Age-Selective Segregation of Organelles

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EC-Contrib. €

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Partnership

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Project "Age Asymmetry" data sheet

The following table provides information about the project.

Coordinator
HELSINGIN YLIOPISTO 

Organization address
address: YLIOPISTONKATU 3
city: HELSINGIN YLIOPISTO
postcode: 14
website: www.helsinki.fi

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Finland [FI]
 Total cost 1˙500˙000 €
 EC max contribution 1˙500˙000 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2015-STG
 Funding Scheme ERC-STG
 Starting year 2016
 Duration (year-month-day) from 2016-05-01   to  2021-04-30

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    HELSINGIN YLIOPISTO FI (HELSINGIN YLIOPISTO) coordinator 1˙500˙000.00

Map

 Project objective

Our tissues are constantly renewed by stem cells. Over time, stem cells accumulate cellular damage that will compromise renewal and results in aging. As stem cells can divide asymmetrically, segregation of harmful factors to the differentiating daughter cell could be one possible mechanism for slowing damage accumulation in the stem cell. However, current evidence for such mechanisms comes mainly from analogous findings in yeast, and studies have concentrated only on few types of cellular damage. I hypothesize that the chronological age of a subcellular component is a proxy for all the damage it has sustained. In order to secure regeneration, mammalian stem cells may therefore specifically sort old cellular material asymmetrically. To study this, I have developed a novel strategy and tools to address the age-selective segregation of any protein in stem cell division. Using this approach, I have already discovered that stem-like cells of the human mammary epithelium indeed apportion chronologically old mitochondria asymmetrically in cell division, and enrich old mitochondria to the differentiating daughter cell. We will investigate the mechanisms underlying this novel phenomenon, and its relevance for mammalian aging. We will first identify how old and young mitochondria differ, and how stem cells recognize them to facilitate the asymmetric segregation. Next, we will analyze the extent of asymmetric age-selective segregation by targeting several other subcellular compartments in a stem cell division. Finally, we will determine whether the discovered age-selective segregation is a general property of stem cell in vivo, and it's functional relevance for maintenance of stem cells and tissue regeneration. Our discoveries may open new possibilities to target aging associated functional decline by induction of asymmetric age-selective organelle segregation.

 Publications

year authors and title journal last update
List of publications.
2019 Nalle Pentinmikko, Sharif Iqbal, Miyeko Mana, Simon Andersson, Armand B. Cognetta III, Radu M. Suciu, Jatin Roper, Kalle Luopajärvi, Eino Markelin, Swetha Gopalakrishnan, Olli-Pekka Smolander, Santiago Naranjo, Tuure Saarinen, Anne Juuti, Kirsi Pietiläinen, Petri Auvinen, Ari Ristimäki, Nitin Gupta, Tuomas Tammela, Tyler Jacks, David M. Sabatini, Benjamin F. Cravatt, Ömer H. Yilmaz, and Pekka
Paneth cell produced Notum attenuates regeneration of aged intestinal epithelium
published pages: , ISSN: 0028-0836, DOI: 10.1038/s41586-019-1383-0
Nature 2019-09-04
2018 Maria M. Mihaylova, Chia-Wei Cheng, Amanda Q. Cao, Surya Tripathi, Miyeko D. Mana, Khristian E. Bauer-Rowe, Monther Abu-Remaileh, Laura Clavain, Aysegul Erdemir, Caroline A. Lewis, Elizaveta Freinkman, Audrey S. Dickey, Albert R. La Spada, Yanmei Huang, George W. Bell, Vikram Deshpande, Peter Carmeliet, Pekka Katajisto, David M. Sabatini, Ömer H. Yilmaz
Fasting Activates Fatty Acid Oxidation to Enhance Intestinal Stem Cell Function during Homeostasis and Aging
published pages: 769-778.e4, ISSN: 1934-5909, DOI: 10.1016/j.stem.2018.04.001
Cell Stem Cell 22/5 2019-09-04

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