Young tissues are effectively renewed and can regenerate after considerable damage. However, as we age, the function of tissue resident stem cells, so-called adult stem cells, decreases and results in reduced regenerative capacity. This slows down recovery from accidents, limits dosing of standard of care drugs such as chemotherapeutics, and will eventually result in the functional decline of all organs and in onset of most age-associated diseases. Strategies maintaining or boosting stem cell capacity of tissue stem cells could therefore have major impact by countering aging-associated vulnerabilities.
In order to undertake their tissue renewing task, stem cells must undergo cell divisions and produce daughter cells that differentiate to the functional cells of the given tissue, and daughter cells that remain as self-renewing stem cells ensuring future tissue renewal. Some stem cells divide asymmetrically to produce these two daughter cells in on division. However, what cellular material is asymmetrically apportioned in such divisions has not been systematically studied, and focus has been on quantitatively asymmetric inheritance of transcription factors. However, we discovered that mitochondria - the organelles central to the cellular metabolism - are segregated qualitatively and age-selectively between daughter cells in asymmetric cell divisions. In this project we study 1) how stem cells recognize the age of their organelles and segregate them age-selectively, 2) what other compartments besides mitochondria are age-selectively segregated, and 3) is age-selective inheritance of organelles lost during aging and can it be promoted to counter aging induced loss of stem cells.
