The effects of obesity mirror those of aging
Researchers identify a shared list of health issues, from DNA damage to cognitive decline
February 25, 2020
Science Daily/Concordia University
Researchers argue that obesity should be considered premature aging. They look at how obesity predisposes people to acquiring the kinds of potentially life-altering or life-threatening diseases normally seen in older individuals: compromised genomes, weakened immune systems, decreased cognition, increased chances of developing type 2 diabetes, Alzheimer's disease, cardiovascular disease, cancer and other illnesses.
Globally, an estimated 1.9 billion adults and 380 million children are overweight or obese. According to the World Health Organization, more people are dying from being overweight than underweight. Researchers at Concordia are urging health authorities to rethink their approach to obesity.
In their paper published in the journal Obesity Reviews, the researchers argue that obesity should be considered premature aging. They look at how obesity predisposes people to acquiring the kinds of potentially life-altering or life-threatening diseases normally seen in older individuals: compromised genomes, weakened immune systems, decreased cognition, increased chances of developing type 2 diabetes, Alzheimer's disease, cardiovascular disease, cancer and other illnesses.
The study was led by Sylvia Santosa, associate professor of health, kinesiology and applied physiology in the Faculty of Arts and Science. She and her colleagues reviewed more than 200 papers that looked at obesity's effects, from the level of the cell to tissue to the entire body. The study was co-authored by Bjorn Tam, Horizon postdoctoral fellow, and José Morais, an associate professor in the Department of Medicine at McGill University.
"We are trying to comprehensively make the argument that obesity parallels aging," explains Santosa, a Tier II Canada Research Chair in Clinical Nutrition. "Indeed, the mechanisms by which the comorbidities of obesity and aging develop are very similar."
From cells to systems
The paper looks at ways obesity ages the body from several different perspectives. Many previous studies have already linked obesity to premature death. But the researchers note that at the lowest levels inside the human body, obesity is a factor that directly accelerates the mechanisms of aging.
For instance, Santosa and her colleagues look at the processes of cell death and the maintenance of healthy cells -- apoptosis and autophagy, respectively -- that are usually associated with aging.
Studies have shown that obesity-induced apoptosis has been seen in mice hearts, livers, kidneys, neurons, inner ears and retinas. Obesity also inhibits autophagy, which can lead to cancer, cardiovascular disease, type 2 diabetes and Alzheimer's.
At the genetic level, the researchers write that obesity influences a number of alterations associated with aging. These include the shortening of protective caps found on the ends of chromosomes, called telomeres. Telomeres in patients with obesity can be more than 25 per cent shorter than those seen in control patients, for instance.
Santosa and her colleagues further point out that obesity's effects on cognitive decline, mobility, hypertension and stress are all similar to those of aging.
Pulling out from the cellular level, the researchers say obesity plays a significant role in the body's fight against age-related diseases. Obesity, they write, speeds up the aging of the immune system by targeting different immune cells, and that later weight reduction will not always reverse the process.
The effects of obesity on the immune system, in turn, affect susceptibility to diseases like influenza, which often affects patients with obesity at a higher rate than normal-weight individuals. They are also at higher risk of sarcopenia, a disease usually associated with aging that features a progressive decline in muscle mass and strength.
Finally, the paper spells out how individuals with obesity are more susceptible to diseases closely associated with later-life onset, such as type 2 diabetes, Alzheimer's and various forms of cancer.
Similarities too big to ignore
Santosa says the inspiration for this study came to her when she realized how many children with obesity were developing adult-onset conditions of diseases, such as hypertension, high cholesterol and type 2 diabetes. She also realized that the comorbidities of obesity were similar to that of aging.
"I ask people to list as many comorbidities of obesity as they can," Santosa says. "Then I ask how many of those comorbidities are associated with aging. Most people will say, all of them. There is certainly something that is happening in obesity that is accelerating our aging process.'"
She thinks this research will help people better understand how obesity works and stimulate ideas on how to treat it.
"I'm hoping that these observations will focus our approach to understanding obesity a little more, and at the same time allow us to think of obesity in different ways. We're asking different types of questions than that which have traditionally been asked."
https://www.sciencedaily.com/releases/2020/02/200225122954.htm
Obesity linked with differences in form and structure of the brain
Science Daily/April 23, 2019
Radiological Society of North America
Researchers using sophisticated MRI technology have found that higher levels of body fat are associated with differences in the brain's form and structure, including smaller volumes of gray matter, according to a study published in the journal Radiology. The findings add important information to our understanding of the connection between obesity and negative health consequences such as dementia.
"MRI has shown to be an irreplaceable tool for understanding the link between neuroanatomical differences of the brain and behavior," said study lead author Ilona A. Dekkers, M.D., from Leiden University Medical Center in Leiden, the Netherlands. "Our study shows that very large data collection of MRI data can lead to improved insight into exactly which brain structures are involved in all sorts of health outcomes, such as obesity."
Obesity represents one of the world's most challenging public health problems. The global pandemic has led to a greater incidence of cardiovascular disease and type 2 diabetes. Previous studies have also tied obesity to an increased risk of accelerated cognitive decline and dementia, suggesting that the disease causes changes to the brain.
To learn more about these changes, the researchers analyzed brain imaging results from more than 12,000 participants in the UK Biobank study, a major trial begun in 2006 to learn more about the genetic and environmental factors that influence disease. The brain scans used sophisticated MRI techniques that provided information on both the neuron-rich gray matter and the white matter, often referred to as the wiring of the brain.
The results show some clear associations in the patients between body fat percentage and brain form and structure, also known as its morphology.
"We found that having higher levels of fat distributed over the body is associated with smaller volumes of important structures of the brain, including gray matter structures that are located in the center of the brain," Dr. Dekkers said. "Interestingly, we observed that these associations are different for men and women, suggesting that gender is an important modifier of the link between fat percentage and the size of specific brain structures."
Analysis showed that, in men, higher total body fat percentage correlated with lower gray matter volume overall and in specific structures involved in the reward circuitry and the movement system. In women, total body fat only showed a significant negative association with the globus pallidus, a structure involved in voluntary movement. For both men and women, higher total body fat percentage increased the likelihood of microscopic changes to the brain's white matter.
The ramifications of these findings, not yet fully clear, could be of significant importance. Smaller gray matter volume suggests loss of neurons, and changes to the white matter could adversely affect the transmission of signals within brain networks. Since the smaller subcortical grey matter volumes are also known to play a role in the food-reward circuitry, these changes may also make it more difficult for obese people to control their weight, Dr. Dekkers said, although more research will be needed to support that connection.
The reason for obesity's adverse effects on the brain are not precisely known. Research has shown that the low-grade inflammation characteristic of obesity can have harmful effects on brain tissue. There is evidence that cellular responses produced in the brain due to inflammation may be behind these effects.
The study looked at overall body fat percentage and did not distinguish between the different types of fat in the body, which Dr. Dekkers said may be an area for additional research. Of particular interest is the visceral white fat found around the abdominal organs. This type of fat, also known as belly fat, is part of metabolic syndrome, a group of factors that increase the risk of cardiovascular disease and diabetes.
"For future research, it would be of great interest whether differences in body fat distribution are related to differences in brain morphological structure, as visceral fat is a known risk factor for metabolic disease and is linked to systemic low-grade inflammation," said the study's senior author, Hildo Lamb, M.D., Ph.D., director of the Cardio Vascular Imaging Group of Leiden University Medical Center.
https://www.sciencedaily.com/releases/2019/04/190423133736.htm