Servizio Comunitario di Informazione in materia di Ricerca e Sviluppo - CORDIS


StemCellGerontoGenes Sintesi della relazione

Project ID: 323136
Finanziato nell'ambito di: FP7-IDEAS-ERC
Paese: Germany

Mid-Term Report Summary - STEMCELLGERONTOGENES (Longevity and aging associated genes that control self-renewal and function of adult stem cells during aging)

A growing list of genes is associated with the development of aging associated pathologies and diseases. These genes are referred to as “gerontogenes”. The functional role of gerontogenes in influencing the aging process remains mostly unknown. We hypothesize that a sub-fraction of gerontogenes influences the aging process by impairing the functionality of stem cells maintaining and regenerating adult organs and tissues thereby leading to the development of aging associated impairments in organ function and an increased risk of disease development. The project “StemCellGerontoGenes” conduct reverse genetic screens to identify gerontogenes that limit the function of stem cells during aging thereby impairing the maintenance of organs and increasing the risk of aging-associated pathologies and diseases.
Work within this project has discovered several genetic factors that limit the functionality of stem cells during aging. In the hematopoietic system, the Per2 gene was identified as a decisive factor limiting the maintenance of lymphoid biased stem and progenitor cells during aging. Of note, the deletion of the gene was sufficient to improve the maintenance of lymphopoiesis and immune functions in aging mice (Wang et al. NCB 2016). Also the project showed, that dietary restriction (DR) – an intervention currently discussed to delay aging – has positive and negative effect on the hematopoietic system. DR delays functional decline of HSCs during aging but compromises its’ capacity to produce lymphocytes. The findings provide experimental evidence that dietary restrictions can have both beneficial and adverse effects on stem cell function and aging (Tang et al. J Ex Med 2016). The study identified new genes that contribute to the induction of aneuploidy – abnormal number of chromosomes - in dividing stem cells. Aneuploidy is thought to contribute to stem cell and tissues aging and to the development of cancer in aging (Meena et al. EMBO J 2015). In the intestinal epithelium, the project identified new mechanisms that contribute to the sensitivity of stem cells to DNA damage and telomeres shortening (Tao et al. EMBO J 1015).
Together, work in the project “StemCellGerontoGenes” has improved our understanding on how genes affect the aging of stem cells and thereby the evolution of aging-associated defects in organ maintenance and disease. The continuation of this work will provide a knowledge basis for the future development of therapies aiming to improve the quality of life during aging and to increase health in the elderly.

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