Research

How does aging occur?  Does each cell determine its own age, regardless of other cells in the body? Or does there exist a hierarchy in which cells coordinate aging across the entire organism so that each tissue and organ age at the same rate? If the latter, which cells and which process would be coordinated, and how? The mechanisms surrounding how individual cells age, whether yeast or mammalian cells grown in culture, have been exhaustively studied and rely on large part to the replicative potential of the cell.   However, how cells within an animal age has largely not been explained.  Work of the Dillin group has broken down the barriers of metazoan aging to reveal that this process is coordinated across the multiple cell types and not merely left to stochastic chance by each individual cell.   Our findings not only reveal which cells perform the coordination, but also the molecules required for communicating aging across cells types and their downstream consequences.

 

One of the major drivers of the aging process is the maintenance of each cell’s proteome.  Conserved from yeast to man, cells have adopted control pathways to ensure the integrity of the proteome.  These control pathways include the unfolded protein response of the endoplasmic reticulum or mitochondria and the heat shock response.   As cells age these control pathways lose their ability to respond to stress and maintain the cell’s proteome.  If an older cell or animal can restore the responsiveness of these control pathways, then it will live longer and healthier. The Dillin group has asked if each of the cells within a metazoan determine their own activity of these control pathways during aging, or has evolution provided master cell types to coordinate the stress response pathways across the entire organism to ensure coordination of aging of the entire organism.  

 

Surprisingly, the Dillin lab’s work finds that coordination of these control pathways from just a few cells can dictate the health and aging of the entire organism.   Our work has identified both neurons and glia to regulate these primordial responses, resulting in massive changes in lifespan.  In fact, in as few as just 4 glial cells, activation of the UPR has profound influence on health and longevity of the nematode C. elegans.   Our work also shows that it is the communication of these stress response pathways from the CNS to the periphery that are essential for successful aging.