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Age Asymmetry SIGNED

Age-Selective Segregation of Organelles

Total Cost €

EC-Contrib. €

Partnership

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Age Asymmetry project word cloud

Explore the words cloud of the Age Asymmetry project. It provides you a very rough idea of what is the project "Age Asymmetry" about.

cellular decline phenomenon apportion yeast discovered accumulation compartments division constantly differ damage tissues time mitochondria aging mammary chronologically cells material maintenance harmful cell accumulate discoveries subcellular mammalian few organelle age slowing analogous induction possibilities renewed relevance young types asymmetrically mechanism compromise first divide selective analyze stem epithelium regeneration proxy differentiating recognize strategy enrich sustained functional property sort underlying segregation asymmetric hypothesize tissue tools daughter vivo chronological protein our human mechanisms concentrated secure renewal mainly

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 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.	FI (HELSINGIN YLIOPISTO)	coordinator	1˙500˙000.00

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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

List of publications.
year	authors and title	journal	last update
2019	Nalle Pentinmikko, Sharif Iqbal, Miyeko Mana, Simon Andersson, Armand B. Cognetta III, Radu M. Suciu, Jatin Roper, Kalle LuopajÃ¤rvi, Eino Markelin, Swetha Gopalakrishnan, Olli-Pekka Smolander, Santiago Naranjo, Tuure Saarinen, Anne Juuti, Kirsi PietilÃ¤inen, Petri Auvinen, Ari RistimÃ¤ki, Nitin Gupta, Tuomas Tammela, Tyler Jacks, David M. Sabatini, Benjamin F. Cravatt, Ã–mer 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, Ã–mer 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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