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04 August 2023 | Story The Conversation | Photo supplied
Claudia Ntsapi
Dr Claudia Ntsapi, Basic Medical Sciences Lecturer at the University of the Free State.

Opinion article by , Basic Medical Sciences Lecturer

As the world population has grown older, Alzheimer’s disease has become increasingly common. Alzheimer’s disease is the most prevalent form of dementia. Dementia is a term used to describe a range of symptoms linked to the decline in brain function with age. Symptoms include memory loss, communication difficulties, problem-solving struggles, and personality or behavioural changes.

Alzheimer’s disease is an increasingly urgent global issue. The World Health Organization predicts that the number of people with the condition will triple by 2050.

Despite this growing problem, Alzheimer’s disease remains a relatively understudied condition. This is particularly the case in sub-Saharan countries such as South Africa. One major challenge is that Alzheimer’s is a complex condition with no known cure. However, researchers have identified several key risk factors associated with the disease. These include age, genetics, lifestyle factors and underlying medical conditions.

In recent years, one of the most promising areas of research on age-related diseases, such as Alzheimer’s disease, has been the accumulation of harmful proteins in the brain. Specifically amyloid-ß. Amyloid-ß has remained a prominent area of research in Alzheimer’s disease as its build-up is a classic feature in the development of the condition. Understanding its involvement in the disease process is crucial for advancing our knowledge and developing effective strategies to diagnose, prevent and treat the disease.

The accumulation of amyloid-ß can lead to the formation of plaques. These plaques can interfere with communication between brain cells. This ultimately contributes to cognitive decline and other symptoms associated with Alzheimer’s disease.

Amyloid-ß is a large membrane protein that is essential in neural growth and repair. But its corrupted form in later life can destroy nerve cells. This triggers the loss of thought and memory that is associated with Alzheimer’s.

We therefore sought to find out if dietary interventions, particularly intermittent fasting, would counteract the accumulation of amyloid-ß in the brain and potentially safeguard against age-related brain cell death.

In a paper published in 2021, my colleague and I showed that in experiments conducted in mice we found that intermittent fasting counteracted amyloid-ß accumulation in the brain. These findings were further confirmed in a paper published in May of 2022.

Our findings are an important contribution to the search for the potential role of dietary interventions and are consistent with previous studies supporting the idea that intermittent fasting may help counteract amyloid-ß accumulation in the brain and protect against age-related brain cell death. To my knowledge, the most recent study using a variation of intermittent fasting, was published in September 2022. The clinical branch of this study remains ongoing.

Research into the causes of Alzheimer’s has gathered pace in recent years with new ground being broken on a regular basis as scientists search for treatments.

Our study’s findings suggest that intermittent fasting may be an effective way to increase the efficiency of autophagy – the process that breaks down and recycles damaged or unnecessary cellular components, such as organelles and toxic proteins. This process can therefore reduce the risk of amyloid-ß build-up and associated brain cell death.

These findings are particularly significant because they shed light on the relationship between autophagy and the death of brain cells with age, and the potential therapeutic benefits of interventions that target this process.

How it works

Intermittent fasting is a dietary approach that involves regulating food intake by alternating periods of fasting and eating. This dietary regimen comprises periods of restricted food consumption, followed by periods of normal eating.

There are different types of intermittent fasting. One is time-restricted eating, where food is consumed within a specific time window each day. Alternate-day fasting is where food is restricted every other day.

Intermittent fasting has been shown to have various health benefits. Some of the benefits relate to the promotion of brain health.

Our study’s findings suggest that intermittent fasting may be an effective way to increase the efficiency of autophagy, an essential process for removing toxic or misfolded proteins that can build up in cells.

Sometimes autophagy doesn’t work properly to remove harmful proteins or other cellular components from cells. This has been strongly implicated in the development and progression of various age-related diseases, and is a target of research for potential therapies.

What we did

In our study we investigated the effects of intermittent fasting on brain cells in mice, and brain cells isolated from mice with increased amyloid-ß toxicity. Mice cells are frequently used as a model for human cells in scientific research. This is because of the significant genetic similarity between mice and humans. This use of animal models allows researchers to gain valuable insights and test hypotheses. It is generally considered ethically preferable before potentially conducting human studies.

We found that 24 to 48 hours of intermittent fasting by mice provided protection against cell death in specific regions of their brain. We noted increased autophagy levels in cells of fasted mice. Even in the presence of a high amyloid-ß protein load in brain cells, intermittent fasting maintained autophagy activity. And the process remained effective over a 21-day treatment intervention period.

By increasing the efficiency of autophagy, it is possible to maintain the removal of harmful proteins in cells, even as we age.

The findings of this study suggest that interventions such as intermittent fasting could potentially protect against the development of age-related diseases. This has important implications for public health.

Intermittent fasting is a relatively simple dietary intervention: it’s easy to do. It has the potential to be widely adopted as a preventive measure against the onset of age-related diseases. These findings also provide a basis for future research into the mechanisms by which intermittent fasting protects against brain cell death, exploring the potential for additional therapeutic interventions that target autophagy, and examining the effects of different fasting regimens on brain health.The Conversation

This article is republished from The Conversation under a Creative Commons license. Read the original article.

News Archive

Inaugural lecture: Prof Robert Bragg, Dept. of Microbial, Biochemical and Food Biotechnology
2006-05-17



Attending the inaugural lecture were in front from the left Prof Robert Bragg (lecturer at the Department of Microbial, Biochemical and Food Biotechnology) and Frederick Fourie (Rector and Vice-Chancellor).  At the back from the left were Prof James du Preez (Departmental Chairperson:  Department of Microbial, Biochemical and Food Biotechnology) and Prof Herman van Schalkwyk (Dean: Faculty of Natural and Agricultural Sciences). Photo: Stephen Collett
 

A summary of an inaugural lecture delivered by Prof Robert Bragg at the University of the Free State:

CONTROL OF INFECTIOUS AVIAN DISEASES – LESSONS FOR MAN?

Prof Robert R Bragg
Department of Microbial, Biochemical and Food Biotechnology
University of the Free State

“Many of the lessons learnt in disease control in poultry will have application on human medicine,” said Prof Robert Bragg, lecturer at the University of the Free State’s (UFS) Department of Microbial, Biochemical and Food Biotechnology during his inaugural lecture.

Prof Bragg said the development of vaccines remains the main stay of disease control in humans as well as in avian species.  Disease control can not rely on vaccination alone and other disease-control options must be examined.  

“With the increasing problems of antibiotic resistance, the use of disinfection and bio security are becoming more important,” he said.

“Avian influenza (AI) is an example of a disease which can spread from birds to humans.  Hopefully this virus will not develop human to human transmission,” said Prof Bragg.

According to Prof Bragg, South Africa is not on the migration route of water birds, which are the main transmitters of AI.  “This makes South Africa one of the countries less likely to get the disease,” he said.

If the AI virus does develop human to human transmission, it could make the 1918 flu pandemic pale into insignificance.  During the 1918 flu pandemic, the virus had a mortality rate of only 3%, yet more than 50 million people died.

Although the AI virus has not developed human-to-human transmission, all human cases have been related to direct contact with infected birds. The mortality rate in humans who have contracted this virus is 67%.

“Apart from the obvious fears for the human population, this virus is a very serious poultry pathogen and can cause 100% mortality in poultry populations.  Poultry meat and egg production is the staple protein source in most countries around the world. The virus is currently devastating the poultry industry world-wide,” said Prof Bragg.

Prof Bragg’s research activities on avian diseases started off with the investigation of diseases in poultry.  “The average life cycle of a broiler chicken is 42 days.  After this short time, they are slaughtered.  As a result of the short generation time in poultry, one can observe changes in microbial populations as a result of the use of vaccines, antibiotics and disinfectants,” said Prof Bragg.   

“Much of my research effort has been directed towards the control of infectious coryza in layers, which is caused by the bacterium Avibacterium paragallinarum.  This disease is a type of sinusitis in the layer chickens and can cause a drop in egg product of up to 40%,” said Prof Bragg.

The vaccines used around the world in an attempt to control this disease are all inactivated vaccines. One of the most important points is the selection of the correct strains of the bacterium to use in the vaccine.

Prof Bragg established that in South Africa, there are four different serovars of the bacterium and one of these, the serovar C-3 strain, was believed to be unique to Southern Africa. He also recently discovered this serovar for the first time in Israel, thus indicating that this serovar might have a wider distribution than originally believed.

Vaccines used in this country did not contain this serovar.  Prof Bragg established that the long term use of vaccines not containing the local South African strain resulted in a shift in the population distribution of the pathogen.

Prof Bragg’s research activities also include disease control in parrots and pigeons.   “One of the main research projects in my group is on the disease in parrots caused by the circovirus Beak and Feather Disease virus. This virus causes serious problems in the parrot breeding industry in this country. This virus is also threatening the highly endangered and endemic Cape Parrot,” said Prof Bragg.

Prof Bragg’s research group is currently working on the development of a DNA vaccine which will assist in the control of the disease, not only in the parrot breeding industry, but also to help the highly endangered Cape Parrot in its battle for survival.

“Not all of our research efforts are directed towards infectious coryza or the Beak and Feather Disease virus.  One of my Masters students is currently investigating the cell receptors involved in the binding of Newcastle Disease virus to cancerous cells and normal cells of humans. This work will also eventually lead to a possible treatment of cancer in humans and will assist with the development of a recombinant vaccine for Newcastle disease virus,” said Prof Bragg.

We are also currently investigating an “unknown” virus which causes disease problems in poultry in the Western Cape,” said Prof Bragg.
 
“Although disinfection has been extensively used in the poultry industry, it has only been done at the pre-placement stage. In other words, disinfectants are used before the birds are placed into the house. Once the birds are placed, all use of disinfectants stops,” said Prof Bragg.

“Disinfection and bio security can be seen as the ‘Cinderella’ of disease control in poultry.  This is also true for human medicine. One just has to look at the high numbers of people who die from hospital-acquired infections to realise that disinfection is not a concept which is really clear in human health care,” said Prof Bragg.

Much research has been done in the control of diseases through vaccination and through the use of antibiotics. “These pillars of disease control are, however, starting to crumble and more effort is needed on disinfection and bio security,” said Prof Bragg.

Prof Bragg has been working in close co-operation with a chemical manufacturing company in Stellenbosch to develop a unique disinfectant which his highly effective yet not toxic to the birds.

As a result of this unique product, he has developed the continual disinfection program for use in poultry. In this program the disinfectant is used throughout the production cycle of the birds. It is also used to ensure that there is excellent pre-placement disinfection.

“The program is extensively used for the control of infectious diseases in the parrot-breeding industry in South Africa and the product has been registered in 15 countries around the world with registration in the USA in the final process,” said Prof Bragg.

“Although the problem of plasmid mediated resistance to disinfectants is starting to rear its ugly head, this has allowed for the opening of a new research field which my group will hopefully exploit in the near future,” he said.

 

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