Scripps Florida Scientists Share $9 Million Grant to Develop Therapies that Target the Aging Process

Scientists from the Florida campus of The Scripps Research Institute (TSRI) and Albert Einstein College of Medicine will share in a $9 million grant from the National Institute on Aging, part of the National Institutes of Health, to study how individual genetic differences may form the basis for new therapeutic approaches that target the aging process itself rather than focusing on the treatment of individual diseases.

Paul Robbins, TSRI professor in the Department of Molecular Medicine and Director of the TSRI Center on Aging and Jan Vijg, professor and chair of genetics of Albert Einstein College of Medicine will lead the study. Approximately half the funding will go to TSRI.

The new five-year study focuses on determining the genetic differences between those people who have aged well and those who have not – differences that can be used to pinpoint new therapeutic targets that could delay or possible even reverse many age-related diseases.

“We call them ‘natural longevity mutants’—human centenarians and super-centenarians who have managed to ward off the diseases that normally begin to plague everyone at middle age,” Robbins said. “They have changes in their genetic makeup that allow them to live to a ripe old age. If we can validate these variants in animal models and test them to see if they live longer, we can begin to develop drugs that increase healthspan.”

It is estimated that in the next 20 years, the number of individuals in the United States over the age of 65 will double, reaching more than 70 million individuals, so the need to identify new therapeutic strategies to extend healthspan—healthy aging—is increasingly urgent.

“It’s a new and intriguing concept: genome to drug,” Robbins said, “These natural occurring human genetic variants are an ideal starting point for our genome-to-drug approach.”

The scientists have already identified multiple genes and pathways that potentially can be manipulated in humans to delay aging through drug treatment—and slow the consequences of its accompanying diseases.

They already have the complete genomes of 660 of these ‘longevity mutants,’ and hope to have 1,500 finished by the end of the first year of the research, Robbins said.

The new studies will make extensive use of a mouse model of accelerated aging created in the laboratory of TSRI Associate Professor Laura Niedernhofer—not only to validate these rare variants but to test and validate compounds that target them.

“We’ve already used the mouse model of accelerated aging to identify some possible targets and pathways for extending healthy aging,” Niedernhofer said. “In fact, several different senolytic drugs and young stem cells are already able to extend healthspan in our models.”

In a recently published study in the journal Nature Communications, Robbins and Niedernhofer identified a new class of drugs that target senescent cells—cells that have stopped replicating because of chromosome damage. As we get older, senescent cells accumulate, becoming a major contributor to age-related diseases. These new compounds have the potential to significantly delay the onset of several age-related symptoms and extend healthy aging.

The number of the grant is 1U19AG056278-01.

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