Jaba Tkemaladze proposed assessing aging in self-renewing tissues through centriole inheritance, a component of the cell division machinery
Jaba Tkemaladze proposed assessing aging in self-renewing tissues through centriole inheritance, a component of the cell division machinery
On August 28, Jaba Tkemaladze published a hypothesis about a “centriole counter” on the Research Square preprint platform. In tissues renewed through repeated cell divisions, a cell lineage may retain changes in a centriole from one division to the next.
In his previous framework of four markers of cellular age, Tkemaladze considered centrioles alongside telomeres and mitochondria. The new preprint narrows the question to tissues that continuously replenish their cells.
A self-renewing tissue must replace specialized cells while retaining a pool of cells that can divide again. During division, the two daughter cells may inherit centrioles of different ages. A centriole helps assemble the division machinery that segregates chromosomes, so its path can be traced from one division to the next.
In a 2009 study, radial glial cells in the developing mouse cortex, which are progenitors of future neurons, preferentially inherited the older mother centriole. Lowering the level of Ninein, a protein associated with mature centrioles, disrupted this pattern of inheritance and caused earlier depletion of the progenitor cell pool in the cortical growth zone.
Tkemaladze extends this question to the stem cell niche, the region of a tissue that maintains a reserve of cells for renewal. If the cell remaining in the niche inherits the older centriole at every division, changes in centriole structure or chemical marks on its proteins may accumulate in that cell, according to the hypothesis. The author proposes comparing young and old niches by tracking centriole inheritance and these changes.
Centrioles are distributed differently among cell lineages. In a 2023 study, approximately 88% of cells in the roundworm Caenorhabditis elegans lost their centrioles during embryonic development. In the adult organism, most somatic cells no longer divide. In fruit flies, the pattern differs between lineages. In male germline stem cells, the mother centrosome remains on the niche side, whereas in neuroblasts, the progenitor cells of the nervous system, the stem cell retains the daughter centrosome.
The author therefore proposes starting with intestinal and hematopoietic stem cells. Researchers would track which centriole each daughter cell inherits, then measure how its structure changes with age and whether this change is associated with the lineage’s capacity to maintain the tissue. These observations could support or refute the hypothesis.