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Unpacking the Complexities of Ageing and Longevity: A Medical Perspective

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An Interview with Dr Sara Bonnes

By Guest Interviewer: Adj Asst Prof Maleena Suppiah Cavert, Chief Wellbeing Officer, National University Health System (NUHS)

Dr Sara Bonnes is an Associate Professor of Medicine at the Mayo Clinic College of Medicine. As an internal medicine doctor, Dr Bonnes’ interest lie in clinical nutrition, resident education, and continuing medical education. In 2020, she was awarded the College of Health and Human Sciences Rising Professional Award by Kansas State University. Additionally, she was recognised as one of the highest-rated teachers in internal medicine residency at Mayo Clinic in 2019. Dr Bonnes received her medical degree from the University of Nebraska College of Medicine and has over 10 years of experience in practice.

What is the current understanding of the ageing process and what causes it at the cellular and molecular levels?

 
Ageing is a complex process. My involvement with ageing has been more from a clinical perspective. Specifically, how we can assess interventions to help patients achieve optimal health spans, being as healthy as they can for as long as possible. The question regarding the ageing process at the cellular and molecular level is really a million-dollar question. If we truly understood that then we would probably be able to have more effective strategies and therapies to help prevent some of the complications of ageing.
 
There have been various discoveries that we have identified as components of the ageing process. You must have heard about telomeres − the kind of protective cap on the end of the DNA. For a while, we thought that was the answer. We have to keep the telomeres happy and keep them growing. And now we are starting to realise that that’s not the answer to everything.
 

However, we do know that cells and their signalling pathways change as time goes on. Cells are normally able to reproduce and divide. Over time, cells tend to become senescent, and eventually, they reach a point where they are not able to reproduce effectively. They also release more pro- inflammatory chemicals. These are chemical signals that cause issues with the cells nearby. As that happens, what can we do about it? Even if we cannot stop cells from ageing, how do we at least inhibit it so that we do not have one cell impacting twenty others or even the whole body? And that’s where we are starting to look into drugs that are called senolytic therapies or senomorphic therapies, to try to stop some of that destructive process that the cells seem to undergo as they age.

What are some of the most promising interventions or treatments for slowing down the ageing process and increasing longevity?

 

Currently, the most evidence-based interventions are these five lifestyle factors: maintaining a healthy weight, exercising regularly, not using tobacco products, alcohol in moderation and having a healthy diet. We are also starting to realise that sleep and stress management are also important. But there are probably more specific data available on the first five factors. And there are still a lot of controversies around what’s ideal in any of those domains.

 

There is also a lot of ongoing work looking at supplements and drugs as well as other therapies. But we are still in the research phase, so we are not yet able to make broad recommendations about those.

The quest to be 18 again

Backed by a team of 30 doctors and spending millions, 45-year- old tech centimillionaire Bryan Johnson has been undergoing an intense data-driven experimental programme called Project Blueprint to unlock the key to ageing. His goal is to reverse the ageing process and have the organs and body of an 18-year-old. Source: Project Blueprint

What about strong social connections and relationships?

 

Yes, it is important for people to have a purpose in life and to feel that they have a sense of why they are continuing. There are a lot of different factors, and we are still trying to understand the effects of their interactions.

 

Among all these factors, exercise seems to be the most consistent and probably the most important. It helps with sleep and stress, and it’s a mood booster overall.

What role does genetics play in determining a person’s lifespan and likelihood of developing age-related diseases?

 

We certainly know that genetics play a role. How long your parents lived does impact how long you think you will live, but we do not have the perfect formula. If diseases impacted your parents and if they were lifestyle-based, today we have more advanced testing and better interventions to help us understand and reduce the impacts. So, we know that genetics play a role, but I do not think we know exactly how much that pre-determines anything.

Talking of genetics or epigenetics, some people take a sample of their saliva and send it to a lab to try to find out whether there are any pre-existing genetic conditions in their DNA they should worry about. This is sometimes known as precision medicine or personalised medicine. What is your view on this?

 

I think there are pros and cons to doing self-DNA testing. If you meet with me as a physician and we are talking about your family history, particularly of dementia or certain other terminal illnesses, we would have a long discussion before I recommended help you understand the context of testing is very important so that people don’t inadvertently do something potentially harmful in their lifestyle or personal behaviours due to misunderstanding the implications.

 

What is the current state of research on anti-ageing drugs, and are there any that have shown promise in clinical trials?

 

There are anti-ageing drugs that have shown promise, but as you get into clinical trials there are positive and negative effects on pretty much everything. Many teams are working on a variety of potential anti-ageing drugs. And medications like rapamycin may have benefits as well. But again, we are not at a stage where we can make broad recommendations about any of these drugs. For certain disease states, there are already approved medications that we use on a regular basis that have shown some benefits and longevity outcomes.

 

Another drug they are studying more is Metformin which we use for patients with impaired fasting glucose or diabetes. Patients who are on that medication do better in the long term, in terms of mortality and other outcomes. It’s not necessarily targeted as an anti-ageing medication, but they are looking at the possibility. I have had patients who needed Metformin for other reasons, and it had testing your DNA. We would also meet with a genetic counsellor to discuss the risks and benefits, and decide whether you really want to know, as well as how you wish to handle things if you test positive for a certain condition.

 

I think there are potential benefits to knowing that you are at risk for certain things. But getting that information without the support of a medical team can sometimes be detrimental because you don’t necessarily know what to do moving forward, or how to support things as you go.

 

On top of that, our DNA testing is still limited. We know that mutation APOE-e4 increases your risk for Alzheimer’s, but having that gene doesn’t mean that you will get Alzheimer’s. Having someone help you understand the context of testing is very important so that people don’t inadvertently do something potentially harmful in their lifestyle or personal behaviours due to misunderstanding the implications.

“THERE ARE ANTI-AGEING DRUGS THAT HAVE SHOWN PROMISE, BUT AS YOU GET INTO CLINICAL TRIALS THERE ARE POSITIVE AND NEGATIVE EFFECTS ON PRETTY MUCH EVERYTHING.

Kicking high and breaking barriers

At the age of 75, Sensei Oshiro Nobuko of the Okinawa Karate-do Shorinryu Taishinkan Association was awarded the rank of 9th-dan in January 2023, making her the highest-ranked female karateka in Okinawa. Photo: Chris Willson / Alamy

What is the current state of research on anti-ageing drugs, and are there any that have shown promise in clinical trials?

 

There are anti-ageing drugs that have shown promise, but as you get into clinical trials there are positive and negative effects on pretty much everything. Many teams are working on a variety of potential anti-ageing drugs. And medications like rapamycin may have benefits as well. But again, we are not at a stage where we can make broad recommendations about any of these drugs. For certain disease states, there are already approved medications that we use on a regular basis that have shown some benefits and longevity outcomes.

 

Another drug they are studying more is Metformin which we use for patients with impaired fasting glucose or diabetes. Patients who are on that medication do better in the long term, in terms of mortality and other outcomes. It’s not necessarily targeted as an anti-ageing medication, but they are looking at the possibility. I have had patients who needed Metformin for other reasons, and it had some very positive outcomes. On the other hand, I have also had patients who have had significant side effects from Metformin. So, we can cause inadvertent harm at times by misapplying things or trying things when we don’t yet have the full evidence. Metformin may very well be helpful as far as ageing goes, but I would like to see more information before I say that’s the answer. For certain medical conditions, there are medications that we know do improve outcomes. We just don’t know that the same outcome can be expected for the broad population.

Beyond the physical

In addition to physical ageing, there is also a growing awareness of the importance of mental and emotional health in later life. Concerns such as loneliness, social isolation and mental health disorders among older adults are receiving greater attention as they have been linked to an increased risk of mortality. Photo: Philippe Leone / Unsplash

How does ageing affect the various systems of the body, such as the cardiovascular, neurological and musculoskeletal systems?

 

Let’s start with the musculoskeletal system – I think that is probably one system where we can really find a lot of changes as we age. We tend to start losing muscle mass within the third decade of our life. We know that muscle strength and muscle mass decrease as we age. Without specific interventions to try to help maintain muscle integrity and strength, we would have an increased risk for frailty, falls and imbalance.

 

The neurovascular ageing process is different for everyone, and our individual health situation plays an important role. Our vision, hearing and mental processes change with age. Those are all very important to us because they affect our sense of space, our ability to communicate and our interpretation of the world around us. And that, in turn, impacts the psychological systems because if I can’t hear and have proper social connections, I will feel more isolated.

 

Changes to cardiovascular systems are certainly associated with age. Many adults tend to develop plaques or other issues, and the resulting narrowing of blood vessels may impede blood flow. We also have an increased risk of developing high blood pressure or other illnesses. The heart muscle is like other muscles — if we do not use it as effectively and regularly as before, it will not function as well as before. We will eventually lose the strength or stamina we used to have.

 

So, there are certainly a lot of different impacts on our systems — some are purely due to ageing, and some are ageing in association with other diseases. But we do know that as you age, you have an increased risk for heart disease such as heart attacks, or developing plaques within arteries, as well as increased blood pressure. You may even have difficulties at times with your heart rhythm not being the same.

Ageing brains and inflammation

A recent study by Harvard researchers, published in the journal Cell, provides new insights into the link between inflammation and cognitive decline in ageing brains. The findings suggest that this decline may be caused by a cellular chain reaction triggered by inflammation. Photo: Bulat Silvia / iStock

Definitely. And I think sarcopenia, or the loss of skeletal muscle mass strength due to ageing, is also associated with menopause in women, am I right? 

 

You are right. There are investigations into how some of these hormonal changes may impact things. We do have female patients who go through premature menopause or need to undergo surgical menopause to treat some other medical conditions. We are beginning to realise that there may be cognitive impacts and functional impacts associated with some of those hormonal changes. So, there is no clear-cut treatment for a single problem. Everything is interconnected.

On top of the impacts on our systems, what is the relationship between ageing and specific chronic diseases such as Alzheimer’s cardiovascular disease, and cancer?

 

As we age, we do have an increased risk for all of these diseases, particularly cancer, as well as Alzheimer’s disease and cardiovascular disease. What is interesting is that we are starting to see more cancer and heart disease in young adults. So, I think we need to separate the pathway we had attributed to ageing from other pathways that are truly impacting us, whether it is molecular signalling, diet and lifestyle factors that we talked about earlier. For example, obesity has certainly gone up, and physical fitness seems to have gone down. So, is it truly ageing or is it some of these other lifestyle factors that we have associated with ageing that may be contributing to the increase in some of these diseases?

 

Although not all replication abnormalities in cells result in cancer, cancer is certainly caused by DNA variants or cells replicating in an abnormal way.

 

But even in the absence of that, old cells can cause inflammation. Inflammation is a term I struggle with because most people understand inflammation as something red and swollen that you get after you fall and scrape your knee. But we are starting to realise that there is a lot more to inflammation than just what we can see, or that we have been able to measure in the traditional sense. There are a lot of chemical signalling pathways that can also trigger inflammation. They can impact our blood pressure, our ability to regulate weight, and our ability to sleep well and be rested. And they may have long-term consequences because they can potentially lead to heart disease, cancer or other diseases.

Beauty has no age

At a fashion show named "Another Look at Old Age" in Paris, France on October 27, 2022, models presented creations by fashion school students from L'Institut Supérieur des Arts Appliqués. The show aimed to promote a more inclusive stance on age and challenge the notion that beauty has an expiration date. Photo: Sarah Meyssonnier / REUTERS

“I THINK HOW WE PERCEIVE THE AGEING PROCESS AND THE RELATIONSHIPS ASSOCIATED WITH IT PROBABLY DOES HAVE A SIGNIFICANT IMPACT ON HOW AGEING AFFECTS US. THOSE WHO ARE OPEN, ACCEPTING AND HAVE STRONGER SOCIAL CONNECTIONS SEEM TO DO BETTER.

What role do environmental factors such as air pollution and exposure to toxins play in ageing and longevity?  

 

I think we are still learning to understand that better. We realised that exposure to certain chemicals or products can certainly lead to inflammation or changes in DNA that seem to accelerate the ageing process or increase our risk of getting some of the diseases we expected to be age-related in the past. What I don’t think we understand is, of all these things that we are exposed to, what may have those health impacts? So far, there is not a comprehensive list of things to avoid and things that are okay. I think we are still learning as we go.

 

On top of that, we have made so many advances in technology in recent years and we are still trying to understand their implications and how certain things may affect our health.

How do societal attitudes and beliefs about ageing impact the physical and mental health of older individuals, and what can be done to change these attitudes?

 

Yeah, I smile because I just read an article that talked about acceptance. People who accept the ageing process and don’t have negative perceptions seem to be happier and live longer and better. I don’t have the exact answer but I think it is probably related to stress and social connections, as well as some of the self-talk we have with ourselves. For example, we can say “Today, I get to go see my grandma and learn from her and share a meal with her,” or we can think of it as an obligation to go see this person and care for this person. Those are two different perspectives that help illustrate how our thinking contributes to our stress, our sense of purpose and well-being, and how we interact with the world around us.

 

I think how we perceive the ageing process and the relationships associated with it probably does have a significant impact on how ageing affects us. Those who are open, accepting and have stronger social connections seem to do better. And I think that also aligns with all the other factors we discussed, like having a purpose and a positive sense of well-being, managing stress, and managing our mood. These are all important as we navigate the ageing process. A Harvard study on ageing found that social connections are important in predicting longevity and that the sense of isolation can have a significant negative impact. We are social beings. Not having social relations really impairs our ability to continue as individuals.

Sedentary lifestyle in young people

A 2019 study by the World Health Organization (WHO) found that more than 80% of adolescents worldwide do not get enough exercise, putting their current and future health at risk. To promote optimal health, the WHO recommends that adolescents engage in at least 60 minutes of moderate to vigorous exercise every day. Photo: Yalana / iStock

WE CAN’T SOLVE THE PROBLEMS OF BEING 65 WHEN WE ARE 65. WE HAVE TO START LOOKING AT IT WHEN WE ARE 45 OR 35 OR 25 TO FIGURE OUT HOW WE CAN LIVE WELL WHEN WE ARE 65, 75 AND 85.”

I think the Harvard study that you referred to is the three-generation longitudinal study done by Professor Robert Waldinger. It found that the No.1 determining factor for health and longevity was relationships. One of my aunts who is 72 just passed on due to an autoimmune disease. But I think the fact that her husband had passed just a year and a half before she did sort of made her not want to fight that hard to live anymore.

 

That is an interesting point as well. When one spouse passes, it’s not uncommon that the other spouse passes within a short period of time. We talk about that kind of relationship impact, but I think there is data to support it as well. This is also expected because this is part of the social connections the Harvard study found important.

The secret to longevity

Jeanne Louise Calment, born on February 21, 1875 in Arles, France, holds the record for being the oldest person ever (female) and the oldest person to ever live, having lived to the age of 122 years and 164 days. She attributed her longevity to a diet that included olive oil, port, and chocolate, and quit smoking at the remarkable age of 120. Sedentary lifestyle in young people A 2019 study by the World Health Organization (WHO) found that more than 80% of adolescents worldwide do not get enough exercise, putting their current and future health at risk. To promote optimal health, the WHO recommends that adolescents engage in at least 60 minutes of moderate to vigorous exercise every day. Photo: Pool New / REUTERS

Is there anything else you would like to share about ageing or longevity, or something that impacts you personally as a physician?

 

In the US, historically, we have labelled 65 and over as the ‘ageing population’. But practically speaking, the decisions we make in our 20s impact our life in our 60s. And so, what I hope to help patients see is that the sooner we intervene and make positive changes in our lifestyle, the better our life will be now and 10, 20 or 30 years from now. I think the one thing we tend to forget is that we can’t solve the problems of being 65 when we are 65. We have to start looking at it when we are 45 or 35 or 25 to figure out how we can live well when we are 65, 75 and 85.

 

I don’t know how to make the 20-year-old listen, but I think we do have a lot to learn. If we start exercising and watching what we eat when we are young, then we won’t have to make huge changes later in life. We should make little changes along the way because we all change as we age. Setting up good habits is not just for adults, but intervention is also for children. We have to make being healthy truly a family activity and celebrate healthy options, and treat special meals as special meals rather than a daily occurrence. And make going for a walk together instead of watching TV an enjoyable experience. Not that we can’t have any ‘fun’, but I think reframing how we think about these things is important.

 

As an Internist, I fully understand that lifestyle changes are difficult and that dealing with chronic health conditions, whether they are associated with ageing or otherwise, is hard. There are a lot of different global health recommendations out there, but what works for you may not work for me, and some of it is trial and error. We sometimes overlook lifestyle changes in the bigger treatment issue, but the effort we put into managing them can certainly have a significant impact on how we view life, how we function and how we are able to carry forward. A lot of my patients feel like they are to be blamed for what happens. “What did I do wrong to have this cancer?”, “I did everything right and why do I still get this?” Well, it’s a lottery and sometimes it’s just bad luck. Beating yourself up with your bad luck is not going to help. The better thing to do is to figure out how to balance what you are dealing with and address the connection between mental and physical health. That can have significant impacts on how things look going forward. 

 

This interview took place at the Mayo Clinic during a visit with The HEAD Foundation in early 2023.

ADJ. ASST. PROF. MALEENA SUPPIAH CAVERT

Dr Suppiah’s career as a food scientist, educator, and healthcare professional spans six countries and over three decades. She keeps healthy through educated nutritional choices, dancing, yoga, swimming, tennis, meditation, and cooking for family and friends.

AUGUST 2023 | ISSUE 11

THE ART, SCIENCE AND GOOD NEWS OF AGEING

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Leaders and changemakers of today face unique and complex challenges. The HEAD Foundation Digest features insights and opinions from those in the know addressing a wide range of pertinent issues that factor in a society’s development. 

Informed opinions can inspire healthy discussions and open up our imagination to new possibilities. Interested in contributing? Write to us at info@headfoundation

Stay updated on our latest announcements on events and publications

About

Leaders and changemakers of today face unique and complex challenges. The HEAD Foundation Digest features insights and opinions from those in the know addressing a wide range of pertinent issues that factor in a society’s development. 

Informed opinions can inspire healthy discussions and open up our imagination to new possibilities. Interested in contributing? Write to us at info@headfoundation

Stay updated on our latest announcements on events and publications

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