Researcher Marcos Arrut proposed three measures for assessing progress toward treating aging
Researcher Marcos Arrut proposed three measures for assessing progress toward treating aging
Arrut addresses which results would indicate progress toward treating aging. He proposes assessing three questions separately: whether intervention is biologically possible, whether it can be controlled within tissues, and whether it has undergone clinical testing in humans.
On 9 August, researcher and entrepreneur Marcos Arrut responded to aging researcher João Pedro de Magalhães during a debate about how quickly science is approaching the ability to treat aging. De Magalhães points to an engineering problem: an intervention must reach the appropriate tissues, work within them, and preserve cell identity. Arrut proposes measuring progress by asking three separate questions: can we alter processes associated with aging in a living organism, can we control such an intervention within tissues, and has it undergone clinical testing in humans?
Full reprogramming can return a cell to an unspecialized state. For this reason, in a 2016 Cell paper, Alejandro Ocampo's team activated four reprogramming factors, OSKM, in mice in repeated cycles. These proteins temporarily alter gene activity. In a mouse model of premature aging, several age-related features improved and lifespan increased. In normally aged mice, the researchers also examined recovery from metabolic dysfunction and muscle injury.
In a 2020 study, researchers activated three factors, OSK, in the mouse retina, the tissue required for vision. In this model, OSK activation was associated with nerve fiber regeneration and improved measures of visual function. Together, these experiments produced results both in the mouse as a whole and in the retina, a tissue with a specific function.
The second measure is control. Partial reprogramming alters gene activity, but the cell must retain its original role. Arrut describes the problem as follows: changes in gene activity that restore youthful cellular features must be separated from those that cause dedifferentiation, meaning the loss of cell identity. Such an intervention therefore requires precise control in each tissue.
“Aging has not been solved” is a fact. “We are far from solving it” is a prediction. That prediction should be tested as rigorously as the idea that a solution is near,” Arrut writes.
The third measure is a clinical trial, which tests whether the intervention can be used in humans. In the first such study, OSK is administered to only one eye to limit the dose and reduce risk to the rest of the body. Experiments in mice address whether the intervention is biologically possible. Control within tissues addresses whether the method can be managed. A clinical trial addresses whether it can be used in humans. Arrut treats these as three separate measures of progress.