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
Insight into cells' 'self-eating' process could pave the way for new dementia treatments
August 21, 2019
Science Daily/University of Plymouth
Cells regularly go through a process called autophagy -- literally translated as 'self-eating' -- which helps to destroy bacteria and viruses after infection.
When it works, this process counteracts neurodegenerative conditions such as dementia and Huntington's Disease, by getting rid of unwanted proteins and their resultant harm to cells.
But when autophagy fails or defects occur, it can give rise to such conditions.
Now new research by the University of Plymouth has shed light on the mechanisms behind autophagy and how it progresses -- particularly relating to a process called liquid-liquid phase separation (LLPS).
The paper was published today (Wednesday 21 August) in Nature Communications, and could provide the first steps towards new treatments for neurodegenerative diseases.
What does the science tell us?
The clearance of cell wastes by autophagy is controlled by two things involving a protein called p62 -- firstly, a chemical process that sees p62 bind a number of identical molecules together (called oligomerisation), and secondly, p62's separation of molecules within cell fluid. The demixing process is called liquid-liquid phase separation (LLPS).
It is crucial to clarify how p62 LLPS is regulated in cells, and scientists have discovered that the process is facilitated by another protein called DAXX.
The study is the first to shed light on this particular protein interaction and its subsequent roles in autophagy and cell protection.
Providing new insights into autophagy, the research helps clarify a key process that might be faltering in those who develop dementia conditions.
What the scientists say
The study was led by Dr Shouqing Luo and his research group from the University of Plymouth's Institute of Translational and Stratified Medicine (ITSMed), in collaboration with Fudan University, Shanghai and Thomas Jefferson University, Philadelphia.
Dr Luo, whose work primarily focuses on finding new autophagy pathways, as well as novel treatments for dementia diseases -- using Huntington's Disease (HD) as a model -- said: "By understanding more about autophagy and the details of the processes involved, we can identify what might be going wrong, and therefore where to target when it comes to tackling neurodegenerative diseases. This research is a major step in helping us to do that.
"The next step for us is to look at applying the science within human cells, so we can further clarify how the protein interaction and the new DAXX function are relevant to neurodegenerative conditions including HD, and whether we can target it to help prevent disease progression.
"HD is an inherited disease that causes the progressive breakdown of nerve cells in the brain. It has a broad impact on a person's functional abilities and currently there is no cure, so it's vital that we continue our work to find out how and why the disease develops."
https://www.sciencedaily.com/releases/2019/08/190821082220.htm