Advanced glycation endproducts, or AGEs, are compounds commonly found in the so-called “Western diet,” and previously have been linked to increased body weight, diabetes, and possibly Alzheimer’s disease. Now, researchers at the Icahn School of Medicine at Mount Sinai have shown that AGEs also cause brain changes similar to Alzheimer’s disease and pre-diabetes. AGEs, which naturally occur at low levels in the body, are found in high levels mostly in heat-processed animal food products, such as grilled or broiled meats; Mount Sinai researchers showed that consumption of such foods by mice raised the body’s level of AGEs, which, among other effects, suppressed levels of sirtuin, or SIRT1, a key “host defense” shown to protect against Alzheimer’s disease as well as metabolic syndrome, a pre-diabetic state.
The studies, suggest that reducing the intake of AGEs could help open “new therapeutic avenues” for the treatment of Alzheimer’s dementia, as well as diabetes. The paper was first published in the journal Proceedings of the National Academy of Sciences.
“Age-associated dementia or Alzheimer’s disease is currently epidemic in our society and is closely linked to diabetes. Our studies of both animals and human subjects confirm that AGE-rich foods are a lifestyle-driven reality with major health implications. The findings point to an easily achievable goal that could reduce the risk of these conditions through the consumption of non-AGE-rich foods, for example, foods that cooked or processed under lower heat levels and in the presence of more water – cooking methods employed for centuries,” said Helen Vlassara, MD, Professor and Director of the Division of Experimental Diabetes and Aging in the Brookdale Department of Geriatrics at Mount Sinai. “While more research needs to be done to discover the exact connection of food AGEs to metabolic and neurological disorders, the new findings again emphasize the importance of not just what we eat, but also how we prepare what we eat. By cutting AGEs, we bolster the body’s own natural defenses against Alzheimer’s disease as well as diabetes.”
Dr. Vlassara and her team of researchers at Mount Sinai previously identified AGEs as a culprit leading to diabetes and increased body weight, and showed that decreasing the intake of AGEs lowers related health risks and restores the body’s natural defenses. For this study, Dr. Vlassara tracked cognitive health in mice (and humans) that ingested AGEs at the high levels typical of a Western diet to determine whether AGEs caused neurodegeneration by suppression of a substance called SIRT1, a deacetylase that regulates neuronal, immune, and endocrine function; SIRT1 is found suppressed in individuals with neurodegenerative and metabolic diseases, such as diabetes or pre-diabetes or simply aging.
The Mount Sinai researchers found that the mice kept on a diet high in AGEs – similar to Western diet – had high levels of AGE in their brains, and suppressed SIRT1 in their blood and brain tissue compared with mice that were fed a diet low in AGEs. Those mice also developed declines in cognitive and motor abilities; and deposits of amyloid-β, a component of the plaques characteristic of Alzheimer’s disease. They also had metabolic syndrome, a combination of medical conditions with increased risk of diabetes and heart disease; The mice fed a low AGE diet remained free of these conditions.
In addition, Dr. Vlassara’s team conducted a clinical study of healthy humans over the age of 60 with high blood levels of AGEs. The study showed that, over a nine-month period, those subjects with high blood levels of AGEs developed cognitive decline, signs of insulin resistance and SIRT1 suppression, while those with low blood AGEs remained healthy. Taken together, these results suggest that consumption of foods high in AGEs can suppress production of SIRT1, contributing over time not only to metabolic syndrome, but also to dementia.
These studies were funded through the National Institutes of Health’s National Institute on Aging and the National Institute of Diabetes and Digestive and Kidney Diseases.
About the Mount Sinai Health System
The Mount Sinai Health System is an integrated health system committed to providing distinguished care, conducting transformative research, and advancing biomedical education. Structured around seven member hospital campuses and a single medical school, the Health System has an extensive ambulatory network and a range of inpatient and outpatient services—from community-based facilities to tertiary and quaternary care.
The System includes approximately 6,600 primary and specialty care physicians, 12-minority-owned free-standing ambulatory surgery centers, over 45 ambulatory practices throughout the five boroughs of New York City, Westchester, and Long Island, as well as 31 affiliated community health centers. Physicians are affiliated with the Icahn School of Medicine at Mount Sinai, which is ranked among the top 20 medical schools both in National Institutes of Health funding and by U.S. News & World Report.