“Work harder, eat less, and, I’m begging you, get a haircut!” A face-to-face meeting between a younger and an older version of yourself would surely be filled with sage advice on how to live life and grow old gracefully. Many scientists wish to recreate such a meeting between young and old neurons to study aging and to learn how to inhibit/reverse unwanted neurological changes, but the inaccessibility of certain tissues complicates such comparisons.
Taking on this challenge, researchers from the stem cell laboratory of Fred H. Gage (Salk Institute for Biological Studies, USA) have now discovered that different cell reprogramming techniques, used to transform one cell type into another, can help us to make such comparisons and thereby begin to understand the aging process.
Their new study, published in Cell Stem Cell, has demonstrated that:
- Two alternative cell reprogramming strategies can create “young” and “old” neurons from donor fibroblast cells from patients of various ages to study aging.
- Reprogramming of fibroblasts to induced pluripotent stem cells and then subsequent differentiation to neurons erased transcriptional changes related to aging and thereby produced “young” neurons from patients of any age.
- Transdifferentiation (or direct reprogramming), which can convert a fibroblast to a neuron without passing through a stem cell-state, did not erase these age-related changes and thereby produced “old” neurons from the same donor cell type.
- Subsequent comparisons highlighted the loss of the RAN-binding protein-17 (RanBP17) in aging neurons.
- RanBP17 belongs to the importin-b family involved in the transport of nuclear proteins through the nuclear pore complex.
- RanBP17 loss promoted undesirable alterations to nucleocytoplasmic compartmentalization, suggesting that loss of nuclear integrity may be tightly linked to adverse neuronal effects during aging.
The next step for these stem cell scientists is to use these cell reprogramming techniques to study aging in patients suffering from neurodegenerative diseases such as Alzheimer’s or Parkinson’s disease to fully understand disease progression and to highlight possible mechanisms to inhibit or reverse unwanted cellular alterations. Looking beyond the brain, the authors also note the importance of their research for aging in other therapeutically relevant human cell types, such as the liver or the heart.
Put your neurons into gear and take a look at this new study before your RanBP17 runs out (Cell Stem Cell, October 2015)!