Rapamycin Prevents Age Related Loss Of Stem Cells

Adult stem cell hang out in most our tissues in a quiet state waiting to be activated in cases of injury or infections. Stem cells have to divide rapidly generating daughter cells that will differentiate into cells to repair tissue in response to injury. Division must be asymmetric generating only one cell during division will go on to differentiate with the other remaining a stem cell.

In order to maintain and preserve stem cells in quiet states and for the prevention of their differentiation and loss low levels of TOR are needed. TOR signaling was observed to become activated in various stem cells types when engaged in a regenerative response, which is important for rapid repair but increases probability of differentiation losing stem cell status. Differentiation loss of stem cell status is prevalent when tissue is under chronic or heavy pressure to regenerate, occurring in response to infections or trauma to tissue. Repeated and/or chronic activation of TOR signalling during the aging process contributes to gradual loss of stem cells. Interventions to limit TOR activity either pharmacological or genetic were able to prevent and/or reverse stem cell loss in muscle and tracheae of aging mice.

It is easy to understand loss of adult stem cells accruing over time and accelerate with aging. There is now a means of rescuing stem cells and boost their ability to maintain healthy tissue, it’s all about maintaining a balance between stem cell differentiation and renewal.

This investigation began in the intestines of fruit flies and then researchers moved on to mice trachea, which tissues share similarities. At different stages of life mice were put on differing rapamycin treatments, researchers observed that rapamycin was to be able to rescue stem cells even when given to the animals starting at 15 months old, which is the equivalent of a human at 50. In every case where a decline in numbers was observed rapamycin would bring it back. It remains to be answered whether the recovery of tissue stem cells was due to replenishment of the stem cell pool from differentiated cells or due to increased asymmetric stem cell divisions.

TOR regulation can be achieved with a number of stimuli, researchers will continue studies to gain a better understanding of how stems cells control activity of this signaling pathway. Homologues of rapamycin are being developed specifically aimed at TOR Complex 1 which is a complex that regulates metabolism and cell growth in all complex organisms.