Dr. Andrea Maier—Mechanisms of Aging

By Longevity by Design, September 13, 2023

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This episode of Longevity by Design discusses topics related to longevity medicine, including mechanisms of aging, biological aging clocks, organ-specific aging, and factors that impact healthspan. With impressive clinical and research experience, Dr. Maier explains the importance of integrating longevity medicine into general practice as well as the current state of diagnostic tools within the field.



About Dr. Andrea Maier

Dr. Andrea Maier is a biogerontologist, internal medicine specialist, geriatrician, and international health policy specialist. She received her MD as a Specialist in Internal Medicine-Geriatrics from the University of Lübeck (Germany). Dr. Maier’s research focuses on unraveling the mechanisms of aging and age-related diseases. She is heading international longitudinal cohort studies and geroscience interventions; she has published more than 370 peer-reviewed articles in the last year.


What are longevity medicine clinics?

To begin the discussion, Dr. Maier defines longevity medicine and discusses the main diagnostic tools used in longevity clinics. 

Dr. Maier describes longevity medicine as “optimizing one’s healthspan while targeting the aging processes across the life course,” elucidating that this model prioritizes whole body health and wellness. Quantifying biological age is the main diagnostic tool in longevity medicine clinics. Dr. Maier says longevity medicine takes an omics approach, examining epigenetic and blood biomarkers to inform biological aging clocks and impute a healthspan score.

Dr. Maier clarifies that this is a very new field, and guidelines and certifications are currently being established


How does longevity medicine differ from conventional medicine?

Dr. Maier has experience as a trained internal medicine physician and in longevity medicine. She provides insight into the differences between these two healthcare models and shares insight into why both are necessary for the optimal health of patients.

  • Traditional medicine: In traditional internal medicine, healthcare providers treat disease. Traditional medicine is also specialized—there are numerous specialties in the medical field. When an individual has a condition, they are referred to a physician who is highly experienced in organ dysfunction related to specific complications.
  • Longevity medicine: In contrast, longevity medicine aims to shift the focus from disease treatment to healthy aging. Longevity medicine clinics target healthspan earlier in life using a lifestyle-based approach to prevent the disease from occurring at all. 

She clarifies that both traditional and longevity medicine have benefits and are most effective when used in conjunction. "I wouldn't say you have to choose one or the other—we can learn a lot from general medical practices." Reflecting on growing up around general practitioners, she expands, "there's plenty of excellent preventative action going on in general medicine. Think about vaccination or measuring the weights of babies—this is all prevention and risk stratification that we use to prevent an age-related disease much later in life." While longevity medicine targets health slightly differently and with newer tools than general practitioners, both healthcare methods are necessary for optimal health.


The importance of merging traditional and longevity medicine

A key message that Dr. Maier emphasizes throughout the episode is the idea that longevity medicine and conventional medicine should be used in conjunction rather than separately. She explains that although epigenetic clocks can be predictive of certain diseases and chronological age, it is still critical to measure and track the biomarkers we already know to predict disease. “I would never say that since we have biological aging clocks we no longer have to measure glucose, HbA1c or blood pressure. These are both excellent markers of diabetes and cardiovascular function.” 

“I really see the entire development of longevity medicine embedded, not separated, into internal medicine. Conventional care is already great—we have to embed longevity medicine into this care and test if the combinations work better.” 

Dr. Maier closes this discussion by explaining the type of aging clock research she hopes to see in the near future. She says that currently, biological aging clocks are studied in isolation. Once scientists start conducting research that compares them with risk factors we already know, we will gain immense information and transform our standard of care.

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How do senescent cells contribute to aging?

Senescent cells are cells within the body that no longer divide. The primary purpose of cellular senescence is still unclear—however, a conceivable hypothesis is that they prevent the reproduction of damaged cells by triggering cell cycle arrest. Furthermore, because cellular senescence accumulates with age, it is considered to be one of the hallmarks of aging. When asked if certain chronic diseases contribute to cellular senescence at a higher rate than others, Dr. Maier references her latest study. 

Dr. Maier’s recent research compares senescent cells in disease-free and disease-containing individuals of the same age. She found that those living with chronic diseases had more senescent cells in their body compared to those who were disease-free. But what’s interesting is that the number of senescent cells present was independent of the location of the organ impacted by the specific disease. “For example, if you take blood from patients with heart failure and compare them to individuals of the same age and sex without heart failure, the diseased individuals have much more senescent cells in the blood but also in the heart.” Noticing this distinction between diseased and non-diseased individuals, Dr. Maier postulates that cellular senescence accumulates with chronological and biological age. It is conceivable that age-related diseases and organ function decline both lead to higher levels of senescent cells compared to age-matched healthy individuals, resulting in a lower biological age for diseased individuals.  

Because studies to date haven’t compared the accumulation of senescent cells across diseases, it is currently unclear if and which diseases result in the most cellular senescence.


How to target cellular senescence through lifestyle interventions

To target senescent cells, Dr. Maier says the best action we can take right now is prevention. "Some studies already show that lifestyle interventions—for example, being on a treadmill for thirty minutes, three times per week—reduce the number of senescent cells in the blood. So, we know that we can manipulate the number of senescent cells, but it isn't clear yet if that, in turn, directly reduces the risk of age-related disease." 


The role of senolytics in targeting cellular senescence

Senolytics—drugs that interfere with senescent cells and induce apoptosis—are currently being researched for safety and efficacy in humans. Dr. Maier notes that while phase one studies show manageable side effects, we are still a few years away from knowing if the senolytic effects are clinically meaningful. 

To close the conversation on senolytics, Dr. Maier explains that there are aspects of cellular senescence which we don’t yet fully understand. “We don’t yet know exactly how many senescent cells we need in our body. Some senescence is necessary to stay healthy—senescence suppresses cancer cells [halting cells that continue to divide]. We have to learn how much we will gain by giving senolytics along with when to administer them.” Further research is required to understand the mechanism of cellular senescence and the gain-risk ratio of using senolytics to alter senescence.


Organ-specific aging

Rate of aging in heart vs. lungs

Following the conversation about senescent cells, Dr. Maier sheds light on research her team has done on organ-specific aging using the United Kingdom (UK) Biobank database. Research shows that the pace of aging within the human body differs by organ, and sometimes one organ experiencing a decline in function can trigger another system to be affected. For example, her team found that a decline in lung function during the first six years of follow-up was highly associated with a decline in heart function in the following six years. Conversely, in participants whose heart function was initially declining, there was no subsequent decline in lung function. This suggests that in the case of the lungs and heart, there may not be a bidirectional associated decline in function but rather a one-way association.


Rate of aging in muscle mass

Interestingly, Dr. Maier’s team also found that the musculoskeletal system is very important and highly interconnected. “If muscle function and muscle mass is declining, that's never a good sign—in fact, muscle decline is a precursor to many other organs declining.” From a clinical perspective, Dr. Maier says it's critical to measure muscle strength and muscle mass as they are critical components to a patient's healthy aging.

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Variation in organ aging

As with many health-related conditions, human aging is highly varied between individuals. Dr. Maier hypothesizes that this variability may explain why there are groups of individuals with more cardiovascular-related diseases at the age of 60 versus others with more neurodegenerative diseases. She closes by saying this between-individual variation is one aspect of human aging that she hopes will get more attention in the coming years. 


Biological aging clocks

A current popular diagnostic tool to measure biological age in longevity medicine is biological aging clocks. Dr. Maier discusses her take on their utility. 

She explains that biological aging clocks measure biological variables in the body, including things like blood pressure, epigenetic makeup, or blood biomarkers. These measurements then get used as predictors for suboptimal outcomes — namely mortality or disease incidence. “These clocks are trained to predict a bad outcome. For me as a clinician, that becomes more relevant in practice because I want to prevent the poor outcome as well as understand who is at risk for that undesirable outcome,” says Dr. Maier.

Dr. Maier discusses what she looks for when selecting a biological aging clock. “I don't have a favorite clock. From an academic point of view, I want an accurate clock. This begs the question, what is the most accurate clock? Opinions on this are a bit diverse in the field, but I would say I only accept a diagnostic marker in clinical practice if the accuracy is at least 80% with a high sensitivity and a high specificity.”


Epigenetic aging clocks

One specific clock that has gained attention and popularity in recent years is the epigenetic aging clock. Epigenetic clocks measure DNA methylation and have been adapted as a means to predict age using epigenetic data.

While these clocks are highly predictive of chronological age, there are still a handful of unknowns related to precisely what DNA methylation means in the context of healthy aging. When asked for her opinion about epigenetic clocks, Dr. Maier explains that she uses them in her clinical practice and she finds them to be very useful. "We use the epigenetic clock in my lab and use five different algorithms at the moment. I'm not convinced that it's necessary to know the reason behind what really happens—namely, which CPG sites are methylated and why this is predictive of aging. As a clinician, I need a biomarker that is sensitive for a certain outcome, so it has to be accurate. In the case of the incidence of diabetes and mortality, these clocks are working very well." She advocates for bringing epigenetic clocks into clinical practice concluding they are a useful tool.


How to lower biological age

Based on current data on biological aging clocks, Dr. Maier recommends the following to lower biological age. "One surprising but logical characteristic is that biologically younger people tend to have more green space around them. This makes sense because these individuals have more space to exercise and walk." She also explains that social connectivity is essential—explaining that individuals who report having supportive friends are biologically younger than those who report being socially isolated. Sleep quality is also a key component of a lower biological age.


Advice to improve healthspan

Dr. Maier’s top tips for healthspan are to eat a healthy diet, exercise, and live a happy life. “I love my work, and therefore I am happy. I have a very nice environment, I have a dog and a husband, and these things make me happy.” She concludes by saying happiness and optimism are strong drivers of healthy longevity.



Longevity by Design

Longevity by Design is a podcast for individuals looking to experience longer, healthier lives. In each episode, Dr. Gil Blander and Ashley Reaver join an industry expert to explore a personalized health journey. The show helps you access science-backed information, unpack complicated concepts, learn what’s on the cutting edge of longevity research and the scientists behind them. Tune into Longevity by Design and see how to add years to your life, and life to your years.

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