Reversing aging in adult stem cells

Researchers from the University at Buffalo have reversed aging in adult stem cells via a single transcription factor called NANOG. Their results, published in the journal Stem Cells, add to our understanding of the aging process and could aid in the development of treatments for various age-related illnesses, including atherosclerosis, osteoporosis and Alzheimer’s disease.

The role of adult stem cells

Found throughout the body, adult stem cells are undifferentiated cells that multiply by cell division to replenish dying cells and restore damaged tissues. Because they can divide indefinitely and regenerate all cell types of the organ from which they originate, adult stem cells have long been a research and therapeutic focus. As people age, however, adult stem cells’ regenerative ability decreases, a process that leads to aging and age-related disorders.

The University at Buffalo researchers, led by Dr. Stelios T. Andreadis, have been studying these effects of aging on adult stem cells. For example, previous research demonstrated that adult stem cells lose the capacity to form muscle cells and generate force as they age. In addition, the team has a National Institutes of Health grant to explore how to reverse the effects of aging on adult stem cells in order to enhance the clinical potential of stem cells isolated from adult donors.

Using NANOG to reverse aging

The new research demonstrates the reversal of the aging process in adult stem cells via NANOG, a transcription factor important for maintaining the self-renewal capacity of undifferentiated stem cells. The team introduced NANOG to aged stem cells, which activated two key cellular pathways: the Rho-associated protein kinase (ROCK) pathway, which helps regulate the cytoskeleton, and the transforming growth factor beta (TGF-β) pathway, which is involved in cellular processes such as cell growth, differentiation and apoptosis.

These pathway activations stimulated dormant actin proteins into generating the cytoskeleton required by adult stem cells to form muscle cells that contract. The forces generated by these muscle cells in turn helped restore the regenerative properties of the stem cells. This restoration was demonstrated in three different models: cells from aged donors, cells aged in culture, and cells from patients with Hutchinson-Gilford progeria syndrome, a premature aging disorder.

The images above show, from left to right, functioning stem cells, stem cells no longer functioning due to Hutchinson-Gilford Progeria syndrome (HGPS), and stem cells previously not functioning due to HGPS that were rebooted by the embryonic stem cell gene NANOG. Credit: Stelios Andreadis.

The next steps

The researchers suggest these results could be applicable to other kinds of cells, such as skeletal and cardiac muscle, because they found that NANOG had activated the central regulator of muscle formation, serum response factor (SRF).

The team is now working to identify drug compounds able to mimic the effects of NANOG, which will allow them to study whether this approach could reverse aging within the human body. If successful, the research could help in treating a variety of age-related disorders, from Alzheimer’s disease to osteoporosis.

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