Living to 100: Decoding the Centenarian Blueprint

Make a Wish: It’s Your 100th Birthday

Can you picture yourself blowing out 100 candles on a birthday cake, surrounded by loved ones decades younger than you? 

If your great-grandaughter asked

you to start a YouTube channel called “Biohacking With Nan,” what tips would you share to help people become centenarians?

Believe it or not, longevity researchers would subscribe to a channel like that.

Don’t believe me?

Between 2020 and September 2023, more than 500 published papers have tried to uncover the biological, genetic, social, and environmental factors correlated with healthy longevity by studying centenarians.

It makes sense. If we want to extend our lifespan, let’s study the experts—those who have seen more days and nights than anyone, and imitate them. 

Not so fast, though. 

Is studying centenarians the optimal way to uncover the secrets of a long and healthy life? 

Only 0.14% of Americans reach age 95+.

What if centenarians are genetically privileged outliers, and trying to imitate their lifestyles is a futile attempt at replication, like eating the same food as LeBron James in hopes of becoming better at dunking basketballs? 

Scientists understand this conundrum well. 

It’s the age-old battle of causation and correlation. In a dynamic world, it’s challenging to identify the exact cause of something. However, progress in longevity research is not halted by this obstacle.

Studying centenarians who experience delayed aging can provide valuable insights into the genetics and biology of longevity.

Research indicates that people who live to be 100 years old tend to have less frequent chronic illnesses. They may develop age-related diseases like high blood pressure, heart disease, cancer, diabetes, stroke, osteoporosis, and Alzheimer’s disease—but they tend to experience these conditions later in life, allowing them to enjoy better health for a more extended period of time.

Now that we comprehend the rationale behind studying centenarians, it’s time to explore one of the most fascinating longevity research questions. 

Did centenarians win the genetic lottery, or is their lifestyle why they celebrate more birthdays than everyone else?

Genetics or lifestyle?

If you tend to complain about how you inherited your father’s nose or your mother’s propensity for breaking out into a song at random moments—I suggest you reconsider.

Research shows your life expectancy may be significantly boosted thanks to your parents.

Offspring of individuals who reach 70 have much better odds of longevity than those whose parents died younger, with the advantage growing as parental lifespan increases. 

The inherited component of longevity is evident in families with exceptional longevity - siblings of centenarians are 4-5 times more likely to live long lives, with women in these families being 8 times as likely and men 17 times as likely to become centenarians themselves. If you have a centenarian at arm’s reach, ask them about their parents. A person who lives to be 100 has parents who are 7 times more likely to live past 90 than the parents of someone with an average lifespan.

You may be thinking, how do we separate genetic and environmental influences on longevity?

Great question.

Researchers rely heavily on studying twins to separate genetic and environmental components. Why? Twins with identical genetic makeups can help isolate the impact of genes and better understand how the environment affects life expectancy. 

Twin studies indicate that genetic differences account for 20% to 40% of human lifespan variation, while environmental factors account for 60% to 80%.

Studies show that the influence of genetics on lifespan increases after age 60, meaning that if you reach that age, your genetic makeup may play a more significant role in contributing to how many additional years you will live. 

However, specific gene variants with substantial beneficial effects on lifespan have been difficult to confirm as the expression and suppression of dozens and even hundreds of genes are thought to hold the key to living longer, so large-scale studies of long-lived families, longitudinal gene association studies, and new analytical methods may enable future progress in understanding the genetics of human longevity.

We all love statistics, but should you despair if your parents didn’t reach ripe ages?

Absolutely not.

Despair is bad for longevity. More on that later.

One of the most fascinating scientific achievements of the study of human health is the discovery that our organism is highly malleable and responsive to our life experiences, psychological makeup, and the environment where we grow and thrive—our body adapts and changes based on the conditions we live in.

We are unlike cars that leave the factory and are stuck with the same engine. We are more like biological software that updates itself based on what the user, you and me, sees, hears, eats, and experiences.

Why is this important for longevity research?

It’s critical because it opens the doors for interventions to extend lifespan. If our biology can change based on behavior and environmental conditions, we can identify those conditions conducive to living long lives and take action to achieve exceptional longevity.

What are the secrets of centenarians? How do they live so long?

Summarizing all the lifestyle characteristics that could impact longevity would require more pages than the entire Game of Thrones series. However, for the sake of illustration, let’s examine a recent study that aimed to contrast the lifestyle differences between non-centenarians and centenarians.

Here are some findings from the study conducted in Zhejiang province, China, along with potential interpretations and my hot takes.

Oral Health

• 20.8% of centenarians use dentures, while 30.7% of non-centenarians do.

Potential interpretation: Good oral health might contribute to longevity.  

Hot take: Perhaps individuals who maintain good oral hygiene tend to prioritize their overall health and well-being?

Dietary Habits

•  8.5% of centenarians include coarse cereals in their diet, contrasting with 0.2% of non-centenarians.

•  26.4% of centenarians consume fruits daily, whereas only 10.9% of non-centenarians do.

Potential interpretation: A diet rich in whole grains and fruits may play a role in living longer.

Hot take: Do phytonutrients in the foods centenarians consume, like fruits, provide protection, or do the foods they avoid, like macadamia milkshakes, contribute to longer lifespans?

Media Consumption

• 12.6% of centenarians frequently watch TV or listen to the radio, as opposed to 20.9% of non-centenarians.

Potential interpretation: Reduced media usage could lead to a longer lifespan.

Hot take: Is media consumption important for longevity, or are the activities centenarians prefer instead of watching The Sopranos, like gardening or Tai Chi, contributing to their long lives?

Loneliness

• 44.3% of centenarians report never feeling lonely, whereas 5.5% of non-centenarians share this experience.

Potential interpretation: Strong social connections may contribute to a longer, more fulfilling life.

Hot take: What if centenarians are more socially active because they’re less sick and have more energy to talk to their neighbors about the weather?

The purpose of sharing the research above is not to treat it as THE study that explains everything about centenarians.

The goal was to show you, while having some fun, the difficulties longevity researchers face when comprehending why some individuals age the way they do and how to extrapolate their findings to the general population to suggest interventions.

Is there a way to solve the issue of being unable to recommend longevity interventions based on isolated studies?

Yes, there might be.

Zones with abnormally high life expectancy could provide more dependable insights into the secrets of long, healthy lives.

Blue Zones

Researchers identified Blue Zones around the world where people enjoy exceptionally long lifespans. 

Five regions recognized as blue zones are:

• Okinawa Prefecture in Japan

• Nuoro Province on the Italian island of Sardinia

• The Nicoya Peninsula in Costa Rica

• The Greek island of Icaria

• Loma Linda, California, in the United States

The usefulness of studying these populations is evident. What sets them apart and enables them to live such long lives?

There are many hypotheses about the uniqueness of these populations.

One of them revolves around physical activity. People living in blue zones apparently walk a lot. 

Wait, now we’re back to where we started.

Is their physical activity high because they are genetically gifted, or does it contribute to their long lives?

Further research, such as double-blind placebo randomized controlled trials, will clarify these mysterious “chicken and egg” scenarios. 

Still, I encourage you to keep an open yet inquisitive mind, as the longevity field will continue advancing exponentially, so it is wise to be cautious before reaching all-encompassing conclusions based on one study or, in this case, the lifestyle habits of Blue Zone populations.

So, what have we learned from the Blue Zones? Do traditional diets and cultural patterns confer protection or reflect another factor?

Studies suggest that walking and physical activity contribute significantly to the longevity of individuals in Blue Zones regions with high concentrations of centenarians.

In the Nicoya Peninsula of Costa Rica, the hilly terrain leads residents to walk long distances daily, contributing to their long and healthy lives. The rugged terrain on the Greek island of Ikaria also demands extensive walking and physical labor like farming and herding.

Do these findings mean that if you start an emu farm atop a mountain, you will live to 100? Probably not, but moving more and becoming involved in moderate physical activities is a low-risk intervention we can all adopt if we aim to live longer.

Blue zone diets have gathered a lot of attention, too. They vary from place to place, but to make things easy for you, people in these places eat mostly plants and not so much meat or sugary snacks.

Blue zone diets offer valuable models to guide researchers and health-conscious individuals. 

The Mediterranean Diet, for example, is a heavily studied diet that includes vegetables, fruits, whole grains, legumes, nuts, olive oil, fish, moderate alcohol intake, and low red meat consumption.

Exciting research shows just how powerful eating a Mediterranean-style diet can be. A 2019 meta-analysis looked at 29 different studies involving over 1.6 million participants. It found that for every 2-point increase in how closely people followed a Mediterranean diet, their risk of dying from any cause decreased by 10%. 

Impressive, right?

Let’s individually analyze some of the components of the Mediterranean Diet so we can better understand why it can be so powerful.

• Fish consumption is typical in long-lived populations like Japan

• Our energy-boosting friends, coffee and tea, have pretty solid science backing them up as pro-longevity drinks

• Olive oil may extend healthspan and prevent neurodegenerative diseases

• Plant-based diets are generally associated with better health and lower mortality.

Longevity depends on avoiding as much as doing. Blue Zone diets differ, but they all emphasize avoiding processed foods linked to various aging diseases and all-cause mortality.

Additional evidence is necessary before recommending the broader adoption of a specific Blue Zone diet for the general population. It is wise to exercise caution in assuming that these diets are universally beneficial for longevity.

Nonetheless, eating more fruits and vegetables (with olive oil) and less ultra-processed foods and sugary drinks, for instance, while including fish, coffee, and tea in your regular diet, is something you can implement today as researchers keep unveiling longevity-enhancing diets.

We have discussed the impact of family history and lifestyle on life expectancy. However, what if a blood test could predict your lifespan?

Biomarkers Clues

Now that we’ve explored the complex interplay between genetics and lifestyle factors in the centenarians’ longevity, it’s time for a more detailed deep dive into physiological biomarkers unveiled by centenarians’ research.

It won’t hurt, I promise.

Several genes have been consistently identified through genome-wide association studies (GWAS) as impacting human longevity. Variants of the APOE gene are associated with differences in lifespan, with one variant linked to increased longevity. Additionally, genes related to cholesterol metabolism, like CETP and LPA, seem to play a role, as higher levels of HDL cholesterol connected to these genes correlate to longer lifespans. 

The insulin/IGF-1 signaling pathway also emerges in longevity studies. The transcription factor FOXO3A, identified by GWAS, is involved in this pathway’s regulation. Variants of FOXO3A correlate to differences in human longevity, indicating this pathway’s importance. 

Aging brings significant changes to the immune system, collectively termed immunosenescence. This dynamic phenomenon affects both natural and acquired immunity, which is crucial in most chronic diseases in older individuals. This process may result in “inflammaging” – a low-grade, chronic inflammation, and a decline in the ability to respond against infections and vaccinations effectively.

An inquisitive 3-year-old could ask,” Why is the sky blue, and more importantly, how is the physiology of centenarians different?

Recent studies reveal that centenarians possess a remarkably diverse gut microbiome compared to younger adults and older individuals, including previously unknown viral genera. This distinctive virome correlates with enhanced antiviral activity and metabolic pathways, suggesting the microbiome may promote longevity, and its uniqueness, as shown by other studies, is correlated with healthy aging and longer lifespans.

Additionally, studies show centenarians exhibit youthful epigenetic patterns resembling those of younger individuals. Specific DNA methylation sites are either preserved in a young state or exhibit advanced regulation around inflammation and disease-related genes, indicating optimized epigenetic control in critical pathways known to impact aging.

How about centenarians’ cognitive function? 

Research is ongoing, but a study found that education significantly influences cognitive health among centenarians. Higher education correlates with better cognitive performance in centenarians. Additionally, maintaining social engagement emerged as a significant predictor of superior cognitive functioning in centenarians. 

A common misconception about longevity is that extending life expectancy prolongs the period when we are more vulnerable. But is this true? Are centenarians more susceptible to disease?

Centenarians and Disease

Low Prevalence of Diabetes

Among centenarians, the prevalence of diabetes is relatively low. At 7.3%, it is less than half of that among the very elderly population aged 85-99 years (18.6%).

Low Prevalence of  High Blood Pressure

Centenarians also exhibit lower rates of hypertension. 38.3% of centenarians are being treated medically or diagnosed, compared to 62.9% of the very old population.

Uncommon Major Cardiovascular Abnormalities

Regarding electrocardiographic characteristics, significant abnormalities like myocardial infarction, atrial fibrillation, and left ventricular hypertrophy are uncommon among centenarians, suggesting that centenarians tend to have healthier hearts with fewer important cardiac issues.

Cardioprotective Molecules

Plasma levels of endogenous cardioprotective molecules and inflammatory mediators are associated with ages up to 115 years. Specifically, NT-proBNP showed age-related distributions, making it a sensitive biomarker for cardiovascular disease even in extreme old age.

Biomarkers and Mortality

High levels of NT-proBNP, interleukin-6, and cystatin C, along with low levels of cholinesterase and albumin, are correlated with an increased risk of all-cause mortality in the oldest people. NT-proBNP, in particular, is strongly linked to survival beyond 105 years of age. 

So, what can we learn from studying centenarians’ biomarkers?

Researchers of supercentenarians (over 110 years old) propose a compelling hypothesis: intrinsic aging in the cardiovascular and renal systems may limit human longevity by disrupting the hemodynamic balance. 

Supercentenarians may have mechanisms that slow cardiovascular aging, indicating more than just robust cardiovascular systems; their bodies may actively slow aging processes, opening up exciting longevity research avenues.

Further research, however, especially into cardiac structure and function, is crucial to validate these ideas.

Limitations and open questions

Centenarians defy the idea that a longer life equals poor health. Instead, they live longer while staying healthier, challenging the notion of compromising health for longevity.

However, are research findings unique to these longevity outliers, or are more broadly applicable? Can we develop interventions based on longevity biomarkers?

You probably know there are no easy answers to these questions, and I’m risking repeating myself and boring both you and me, so I won’t insist on the need for caution.

Recent research on biomarkers of longevity provides reliable guidance for improving interventions that promote longevity.

The lack of standardized criteria and consensus on what constitutes a reliable aging biomarker is a challenge. Identifying reliable biomarkers and validating them for clinical use remains complex, as lifestyle factors may significantly influence biomarker utility in interventions. Therefore, it is crucial to comprehend the connections between genetics and the environment.

Future research must address these challenges and refine the utilization of biomarkers in clinical trials and practice.

We’re embedded in understanding probably the most profound question humans can ask themselves: Can we postpone death?

Here is a non-exhaustive list of questions that studying centenarians opens up. I will not try to answer them, but I invite you to ponder them on one of those nights when sleep eludes you.

How Can We Reconcile the Idiosyncratic Behaviors of Centenarians?

We are familiar with the standard reporting of a centenarian’s birthday. The birthday person is not very excited about the media attention; they wear a questionable party hat and attribute their long life to drinking Red Bull every night while listening to crime podcasts. 

All jokes aside, research has found that some centenarians engage in typically considered unhealthy behaviors, such as drinking alcohol, smoking, and indulging in certain foods, like sugary treats. How can this be? Does this challenge the idea that extreme longevity is linked to healthy lifestyles? Do they have protective genetic characteristics?  

How Relevant Is Our Family History? 

Research suggests an inherited component to extreme longevity, but how important is it? Can we break our genetic “barriers” by taking action and, in a way, “cheat” death?

Can We Mimic Centenarian Phenotypes?

A remarkable characteristic of centenarians is how they delay disease. Centenarians experience diseases of aging much later in life than the general population. Cancer, cardiovascular disease, osteoporosis, stroke, dementia, and hypertension manifest even decades later in centenarians than in ordinary people. 

Can individuals mimic the physical traits and resistance to disease seen in centenarians, even if they do not possess the same genetic makeup? Can one extend one’s life expectancy through thoughtful and deliberate behaviors?

The Road Ahead

The existence of people who live to be 100 years old raises complex scientific and philosophical inquiries that cannot be easily resolved.

Are there boundaries to human lifespan, or can we shatter them, much like Usain Bolt smashed Olympic records?

These are not mere theoretical questions. In a way, they are radically practical.

The global population aged 60 years or over has increased significantly, numbering 962 million in 2017, more than double the figure from 1980 (382 million). It is projected to reach almost 2.1 billion by 2050. Likewise, individuals aged 80 years or over are expected to increase more than threefold from 137 million in 2017 to 425 million by 2050. 

Aren’t you curious about how healthy you will be then and what decisions you are making today to get there in the first place?

Longevity research is the science of hope, as understanding centenarians’ genetics, biomarkers, and physiology could provide a roadmap to tackle society’s most pressing health needs.

The road ahead has missing pieces—that’s okay—this is the biggest enterprise humanity has embarked upon.

In a field riddled with questions, it feels right to end with another: 

Will you be here in a hundred years?