We live in a society obsessed with aging (and how to slow it down), but surprisingly little is known about the human aging process because lifespans of eight decades or more make it difficult to study. Researchers in the lab of Juan Carlos Izpisúa Belmonte recently replicated premature aging in the lab, however, allowing them to study aging-related disease in a dish.
In their study, published in the journal Nature, Izpisúa Belmonte and his team successfully generated induced pluripotent stem (iPS) cells from skin cells obtained from patients with Hutchinson-Gilford progeria, who age eight to ten times faster than the rest of us, and differentiated them into smooth muscle cells displaying the telltale signs of vascular aging. Progeria's striking features resemble the aging process put on fast-forward, and afflicted people rarely live beyond 13 years. Almost all patients die from complications of arteriosclerosis—the clogging or hardening of arteries or blood vessels caused by plaques—which leads to heart attack and stroke. Scientists are particularly interested in progeria in the hope that it might reveal clues to the normal human aging process. The disease is exceedingly rare, however, and only 64 children living with progeria are known, making access to patients very difficult.
Progeria stems from a mutation that leads to the production of a truncated version of the protein known as progerin. Cells from progeria patients have misshapen nuclei and a range of other defects. Yet despite their "old" appearance and against all predictions, it turned out that these cells could be readily converted into iPS cells. The reprogramming process erased all apparent defects, and the rejuvenated pluripotent cells looked and acted like perfectly normal healthy cells. But as soon as Izpisúa Belmonte's group differentiated progeria-derived iPS cells into smooth muscle cells, the evidence of premature aging reappeared.
This suppression of progerin expression by reprogramming and subsequent reactivation during differentiation provides a unique model system to study human premature aging pathologies, notes Izpisúa Belmonte, and having a human model of accelerated aging may provide new insights into how we age.
In a later study, published in Cell Stem Cell, Izpisúa Belmonte's team successfully edited a diseased gene in patient-specific iPS cells as well as adult stem cells, demonstrating that the geneediting approach they developed provides an efficient and safe tool for cell engineering and opens the way for gene editing-based stem cell therapies suitable for clinical applications.