Aging Slowed in Mouse Model by Blocking Key Protein

Blocking a protein that regulates the activity of certain genes slowed the aging process in a mouse model of premature aging, as well as in healthy mice, according to researchers at the University of Pittsburgh School of Medicine. Their findings, published online ahead of print in the Journal of Clinical Investigation, could lead to drugs that prevent cellular damage due not only to growing old, but also to cancer and diseases caused by abnormal DNA repair activity.

Aging is thought to be the result of accumulated cellular damage, including DNA damage, but the biological mechanisms that drive aging in response to damage are not understood, said senior author Paul Robbins, Ph.D., professor in the Department of Microbiology and Molecular Genetics at Pitt’s School of Medicine.  His team studied NF-kappa B, a protein involved in turning certain gene activity on and off in response to inflammation, stress and cellular damage.

“Other studies have shown that NF-kappa B activity is elevated in aging tissues,” Dr. Robbins said. “We examined whether this held true for mice with progeria, a disease of accelerated aging, and what would happen if we blocked NF-kappa B activation.”

The researchers found that a higher percentage of cells contained activated NF-kappa B in old and progeroid mice than in healthy adult mice. Age-related activation of NK-kappa B is stochastic, meaning it happens in some but not all cells, they said.

Altering expression of NF-kappa B slightly or blocking its activation with chemicals led to a delay in the onset and reduction in severity of age-related changes in tissues, including muscle, liver, kidney and the nervous system.  Researchers also found that inhibiting the protein reduced free radical-induced oxidative damage.

“It’s possible that as we age, NF-kappa B becomes activated by accumulation of cellular damage, and that in turn increases the product

on of free radicals, resulting in more cell damage,” Dr. Robbins said. “An agent that blocks this protein could be used to slow down aging and also to treat certain cancers and diseases such as xeroderma pigmentosum, which are characterized by altered DNA repair activity.”



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