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Molecular Medicine Partnership Unit


Early warning signals of ageing in human stem cells

Anne-Claude Gavin and Anthony D. Ho
Anne-Claude Gavin and Anthony D. Ho

Anthony D. Ho and Anne-Claude Gavin

Our research interest

The regenerative power of a living organism is linked to the potential of its stem cells to replace the corresponding damaged tissue. A living organism is therefore as old as its stem cells. Surprisingly little is known about the impact of time and age on the basic units of life, the stem cells. Using hematopoietic stem cells (HSC) and their microenvironment as a model, our long-term goal is to define the molecular mechanisms of ageing in somatic stem cells and means to correct these age-related alterations. The experimental approaches are (1) identification of candidate genes and proteins by expression analyses of HSC as well as mesenchymal stromal cells (MSC) derived from different age groups, (2) correlation of cell biological characteristics with ageing specific alterations in genomes and proteomes; (3) analysis of acetylation, phosphorylation of candidate genes associated with ageing; (4) relationship of these alterations to development of myelodysplastic syndromes (MDS) as a model for a typical age specific disease.



Besides loss of functions, reduced capacity to regenerate tissues or organs upon injury and a propensity to infections and cancers are the most prominent hallmarks of senescence. The regenerative prowess of a living organism is linked to the ability and potential of its stem cells to replace the corresponding damaged tissue. Whereas the vulnerability to infectious disease and cancer is associated with a decline of the immune system, the latter is in turn a sum product of interactions among hematopoietic stem cells (HSC), the microenvironments in the bone marrow, among others. Hence both phenomena can be interpreted as as signatures of ageing at the level of somatic stem cells. HSC and the bone marrow niche are ideal models for studies on the influence of time, age and environment on somatic stem cells.



  • To define the fundamental molecular and cell biological mechanisms of ageing in HSC.
  • To understand the roles of genetic and proteomic alterations on the process of ageing.
  • To determine the molecular and cellular alterations of MSC with ageing, and their impact on supportive function for HSC.
  • To combine the cell biological, proteomic, and genetic studies for a better systems understanding of age-related diseases such as MDS


Research Focus 1

To define the fundamental molecular and cell biological mechanisms of ageing of HSC

An understanding of the cellular and molecular mechanisms that regulate self-renewal and differentiation of HSC, as well as their alterations with ageing will provide a basis for prevention and treatment of diseases associated with old age such as myelodysplastic syndromes (MDS). 
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Research Focus 2

To determine the molecular and cellular alterations of MSC upon ageing, and their impact on supportive function for HSC

There is overwhelming evidence that the stem cell niche plays a significant role for the ageing process in adult stem cells. 
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Research Focus 3


SyStemAge is uniquely positioned to bridge the gap between the clinical, biomedical and natural sciences and immediately contribute to bio-gerontology.
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Important publications

The orchestra of lipid-transfer proteins at the crossroads between metabolism and signaling. Chiapparino A, Maeda K, Turei D, Saez-Rodriguez J, Gavin AC.
Prog Lipid Res. 2016 Jan;61:30-9. doi: 10.1016/j.plipres.2015.10.004. Epub 2015 Dec 1. Review.PMID:26658141

The systematic analysis of protein-lipid interactions comes of age.
Saliba AE, Vonkova I, Gavin AC.
Nat Rev Mol Cell Biol. 2015 Dec;16(12):753-61. doi: 10.1038/nrm4080. Epub 2015 Oct 28. PMID: 26507169

Pre-transplant weight loss predicts inferior outcome after allogeneic stem cell transplantation in patients with myelodysplastic syndrome.
Radujkovic A, Becker N, Benner A, Penack O, Platzbecker U, Stölzel F, Bornhäuser M, Hegenbart U, Ho AD, Dreger P, Luft T.
Oncotarget. 2015 Oct 27;6(33):35095-106. doi: 10.18632/oncotarget.4805.

Lipid Cooperativity as a General Membrane-Recruitment Principle for PH Domains.
Vonkova I, Saliba AE, Deghou S, Anand K, Ceschia S, Doerks T, Galih A, Kugler KG, Maeda K, Rybin V, van Noort V, Ellenberg J, Bork P, Gavin AC.
Cell Rep. 2015 Sep 1;12(9):1519-30. doi: 10.1016/j.celrep.2015.07.054.
Epub 2015 Aug 20. PMID: 26299969


A Conserved Circular Network of Coregulated Lipids Modulates Innate Immune Responses.
Köberlin MS, Snijder B, Heinz LX, Baumann CL, Fauster A, Vladimer GI, Gavin AC, Superti-Furga G.
. 2015 Jul 2;162(1):170-83. doi: 10.1016/j.cell.2015.05.051. Epub 2015 Jun 18. PMID:26095250


Functional fingerprinting of human mesenchymal stem cells using high-throughput RNAi screening.
Erdmann G, Suchanek M, Horn P, Graf F, Volz C, Horn T, Zhang X, Wagner W, Ho AD, Boutros M.
Genome Med. 2015 May 17;7(1):46. doi: 10.1186/s13073-015-0170-2. eCollection 2015. PMID: 26120366

Quantitative mass spectrometry of posttranslational modifications: keys to confidence.
Hennrich ML, Gavin AC.
Sci Signal.
2015 Apr 7;8(371):re5. doi: 10.1126/scisignal.aaa6466. Review. PMID:25852188


Modules, networks and systems medicine for understanding disease and aiding diagnosis.
Gustafsson M, Nestor CE, Zhang H, Barabási AL, Baranzini S, Brunak S, Chung KF, Federoff HJ, Gavin AC, Meehan RR, Picotti P, Pujana MÀ, Rajewsky N, Smith KG, Sterk PJ, Villoslada P, Benson M.
Genome Med. 2014 Oct 17;6(10):82. doi: 10.1186/s13073-014-0082-6. eCollection 2014.


Opens external link in new windowSnapShot: protein-protein interaction networks. 
Seebacher J. and Gavin A.C. (2011)
Cell 2011 March18, 144, 1000

Opens external link in new windowDNA methylation pattern changes upon long-term culture and aging of human mesenchymal stromal cells.
Bork S, Pfister S, Witt H, Horn P, Korn B, Ho AD, Wagner W.
Aging Cell 2010 Feb;9(1):54-63.

Opens external link in new windowCo-Culture with Mesenchymal Stromal Cells Increases Proliferation and Maintenance of Hematopoietic Progenitor Cells.
Walenda T, Bork S, Horn P, Wein F, Saffrich R, Diehlmann A, Eckstein V, Ho AD, Wagner W.
J Cell Mol Med. 2010 Jan;14(1-2):337-50.

Opens external link in new windowTranscriptome complexity in a genome-reduced bacterium. 
Güell M., van Noort V., Yus E., Chen W.-H., Leigh-Bell J., Michalodimitrakis K., Yamada T., Arumugam M., Doerks T., Kühner S., Rode M., Suyama M., Gavin A.C., Bork P. and Serrano L. 
Science 2009 326, 1268-1271.

Opens external link in new windowAging and replicative senescence have related effects on human stem and progenitor cells
Wagner W, Bork S, Horn P, Krunic D, Walenda T, Diehlmann A, Benes V, Blake J, Huber FX, Eckstein V, Boukamp P, Ho AD. 
PLoS One 2009 Jun 9;4(6):e5846.


Opens external link in new windowResearch group's MMPU link to EMBL web page



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