Animal Study Shows Rapamycin May Prevent Age-Related Brain Vascular Deterioration


Could an immunosuppressant boost cognition in senior citizens? A recent animal study from UT Health San Antonio suggests the possibility. The study shows age-related decreases in blood flow to the brain and memory loss can be modified with the drug rapamycin.

Recent research in the Framingham Heart Study led by Sudha Seshadri, formerly of Boston University and founder of the Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases at UT Health San Antonio, has shown that among the risk factors for Alzheimer’s disease is a reduction of blood flow to the brain. Neurons require glucose and oxygen to function and blood vessels supply those necessary components. When the blood flow is reduced, so too are the requirements the brain needs.

The UT Health San Antonio study, which was published this week in the journal Aging Cell, found that rats who were dosed with rapamycin maintained solid blood flows in their brains through the end of life. The lab animals were fed food laced with the medication beginning at the age of 19 months, which is about middle age for rats, and the dosing continued until they were 34 months old, which is considered an advanced age for rats. Senior study author Veronica Galvan said 34 months, this is about as old as rats will get and brain scans showed that even at an advanced age, the blood flow in the brains of the animals was “exactly the same as when they started treatment.” Galvan is a researcher with the university's Sam and Ann Barshop Institute for Longevity and Aging Studies and Biggs Institute. 

If the findings hold throughout continued studies, research first author Candice Van Skike suggested that treatment with rapamycin could hold implications in preventing Alzheimer’s disease or other forms of dementia in some people. The study followed the natural aging patterns of the animals. Van Skike said the researchers did not engineer disease states or the like in the animals.

Van Skike said that untreated aged rats that took part in the study mirrored the loss of blood flow to the brain and the loss of memory that is observed in adult humans who are of advanced years.

“We were looking at just regular aging. These rats had natural cognitive decline that was not provoked by a forced disease process,” Van Skike said in a statement provided by the university. “In contrast, the old rats treated with rapamycin looked like middle-aged rats in our study.”

Rapamycin inhibits the activation of both T cells and B cells by reducing sensitivity to interleukin-2 through the inhibition of mTOR, a “master controller” of cell growth and aging. Galvan said the results of the rat study provide “very good evidence” that “TOR drives the loss of synapses and cerebral blood flow during aging.”

Seshadri, who led the Framingham Heart study, said researchers are already studying the safety of rapamycin in people with mild cognitive impairment, a precursor to dementia. She said it is exciting that rapamycin may “help preserve the integrity of brain circulation and memory performance in older adults.”

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