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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

Media: Sunday Times
2006-05-20

Sunday Times, 4 June 2006

True leadership may mean admitting disunity
 

In this edited extract from the inaugural King Moshoeshoe Memorial Lecture at the University of the Free State, Professor Njabulo S Ndebele explores the leadership challenges facing South Africa

RECENT events have created a sense that we are undergoing a serious crisis of leadership in our new democracy. An increasing number of highly intelligent, sensitive and committed South Africans, across class, racial and cultural spectrums, confess to feeling uncertain and vulnerable as never before since 1994.

When indomitable optimists confess to having a sense of things unhinging, the misery of anxiety spreads. We have the sense that events are spiralling out of control and that no one among the leadership of the country seems to have a definitive handle on things.

There can be nothing more debilitating than a generalised and undefined sense of anxiety in the body politic. It breeds conspiracies and fear.

There is an impression that a very complex society has developed, in the last few years, a rather simple, centralised governance mechanism in the hope that delivery can be better and more quickly driven. The complexity of governance then gets located within a single structure of authority rather than in the devolved structures envisaged in the Constitution, which should interact with one another continuously, and in response to their specific settings, to achieve defined goals. Collapse in a single structure of authority, because there is no robust backup, can be catastrophic.

The autonomy of devolved structures presents itself as an impediment only when visionary cohesion collapses. Where such cohesion is strong, the impediment is only illusory, particularly when it encourages healthy competition, for example, among the provinces, or where a province develops a character that is not necessarily autonomous politically but rather distinctive and a special source of regional pride. Such competition brings vibrancy to the country. It does not necessarily challenge the centre.

Devolved autonomy is vital in the interests of sustainable governance. The failure of various structures to actualise their constitutionally defined roles should not be attributed to the failure of the prescribed governance mechanism. It is too early to say that what we have has not worked. The only viable corrective will be in our ability to be robust in identifying the problems and dealing with them concertedly.

We have never had social cohesion in South Africa — certainly not since the Natives’ Land Act of 1913. What we definitely have had over the decades is a mobilising vision. Could it be that the mobilising vision, mistaken for social cohesion, is cracking under the weight of the reality and extent of social reconstruction, and that the legitimate framework for debating these problems is collapsing? If that is so, are we witnessing a cumulative failure of leadership?

I am making a descriptive rather than an evaluative inquiry. I do not believe that there is any single entity to be blamed. It is simply that we may be a country in search of another line of approach. What will it be?

I would like to suggest two avenues of approach — an inclusive model and a counter-intuitive model of leadership.

In an inclusive approach, leadership is exercised not only by those who have been put in some position of power to steer an organisation or institution. Leadership is what all of us do when we express, sincerely, our deepest feelings and thoughts; when we do our work, whatever it is, with passion and integrity.

Counter-intuitive leadership lies in the ability of leaders to read a problematic situation, assess probable outcomes and then recognise that those outcomes will only compound the problem. Genuine leadership, in this sense, requires going against probability in seeking unexpected outcomes. That’s what happened when we avoided a civil war and ended up with an “unexpected” democracy.

Right now, we may very well hear desperate calls for unity, when the counter-intuitive imperative would be to acknowledge disunity. A declaration of unity where it manifestly does not appear to exist will fail to reassure.

Many within the “broad alliance” might have the view that the mobilising vision of old may have transformed into a strategy of executive steering with a disposition towards an expectation of compliance. No matter how compelling the reasons for that tendency, it may be seen as part of a cumulative process in which popular notions of democratic governance are apparently undermined and devalued; and where public uncertainty in the midst of seeming crisis induces fear which could freeze public thinking at a time when more voices ought to be heard.

Could it be that part of the problem is that we are unable to deal with the notion of opposition? We are horrified that any of us could be seen to have become “the opposition”. The word has been demonised. In reality, it is time we began to anticipate the arrival of a moment when there is no longer a single, overwhelmingly dominant political force as is currently the case. Such is the course of history. The measure of the maturity of the current political environment will be in how it can create conditions that anticipate that moment rather than seek to prevent it. We see here once more the essential creativity of the counter-intuitive imperative.

This is the formidable challenge of a popular post-apartheid political movement. Can it conceptually anticipate a future when it is no longer overwhelmingly in control, in the form in which it is currently, and resist, counter-intuitively, the temptation to prevent such an eventuality? Successfully resisting such an option would enable its current vision and its ultimate legacy to our country to manifest in different articulations, which then contend for social influence. In this way, the vision never really dies; it simply evolves into higher, more complex forms of itself. Consider the metaphor of flying ants replicating the ant community by establishing new ones.

We may certainly experience the meaning of comradeship differently, where we will now have “comrades on the other side”.

Any political movement that imagines itself as a perpetual entity should look at the compelling evidence of history. Few movements have survived those defining moments when they should have been more elastic, and that because they were not, did not live to see the next day.

I believe we may have reached a moment not fundamentally different from the sobering, yet uplifting and vision-making, nation-building realities that led to Kempton Park in the early ’90s. The difference between then and now is that the black majority is not facing white compatriots across the negotiating table. Rather, it is facing itself: perhaps really for the first time since 1994. Could we apply to ourselves the same degree of inventiveness and rigorous negotiation we displayed leading up to the adoption or our Constitution?

This is not a time for repeating old platitudes. It is the time, once more, for vision.

In the total scheme of things, the outcome could be as disastrous as it could be formative and uplifting, setting in place the conditions for a true renaissance that could be sustained for generations to come.

Ndebele is Vice-Chancellor of the University of Cape Town and author of the novel The Cry of Winnie Mandela

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