Why Are More and More People Living to 100?
Having had the personal experience of seeing parents and loved ones struggle through the last few years of life, often admitting that they would much prefer to die than to go on with the consequences of physical and mental decline, I wonder about the fascination of scientists to unravel the biological keys to super longevity, and the growing popularity of books and online information dealing not only with how to live to 100 and beyond, but even reach immortality.
“…millions of years of evolution on our planet have come up with this universal cycle of birth and death…”
Ageing and dying are natural parts of life. Millions of years of evolution on our planet have come up with this universal cycle of birth and death, optimizing reproductive and survival mechanisms, including age-adjusted muscle strength, cardiovascular and pulmonary function, and reaction times at certain ages when there is a particular need for these functions, and a slow functional decline towards the end of life, when they are no longer essential for survival. In my opinion, these are basic facts that we should accept as the wisdom of evolution.
So, do we really want to alter a system that has evolved to provide immense adaptive value for us living in harmony with this planet, and risk major disruptions in the planetary ecosystem by trying to change it? And what about the psychological, sociopolitical, and economic problems that rapidly aging societies with low birthrates, like Japan, South Korea and China have been experiencing?
….[should our goal be] to enable healthy aging with minimal medical and surgical interventions within the biological bandwidth?”
Or should we primarily be interested in interventions that build on conserved mechanisms of aging, and optimize these systems through lifestyle modifications, with the primary goal being not to prolong the human lifespan beyond its evolutionary programmed upper limit, but to enable healthy aging with minimal medical and surgical interventions within the biological bandwidth?
As described by Patricia S. Daniels in the Feb 7, 2023 issue of the National Geographic magazine, two basic mechanisms have been implicated in the natural aging process. According to Daniels, “…one group of theories holds that the body ages because of wear and tear that accumulates in the tissues over the years. Waste products build up in cells, backup systems fail, repair mechanisms gradually break down, and the body simply wears out like an old car. The second group of theories says that aging is driven by our genes—by an molecular clock set to a particular timetable for each species.” As I will discuss in this post, there is evidence for both of these theories. Biologists point out that from an evolutionary point of view, the effects of natural selection greatly decline after reproductive age, as evolution favors genes that are beneficial early in life, putting the body’s resources into reproduction and leaving fewer available for long-term maintenance”.
“…current population trends around the world seem to be moving into a different direction as evolution had in mind.”
However, current population trends around the world seem to be moving into a different direction as evolution had in mind. For poorly understood reasons, falling birthrates and increasing longevity have been going hand in hand in several countries around the world, turning large portions of these countries into what have been called Blue Zones. According to the Blue Zone concept, there are geographic regions around the world with an unusually high proportion of individuals living into their hundreds, so called centenarians. However, a closer look at epidemiological trends tells us that this phenomenon is not restricted to Blue Zones any more. Based on a 2022 estimate by the United Nations, there are currently 593,000 centenarians around the world and this population is growing fast. The UN projects there will be 3.7 million centenarians alive by 2050.
Even though centenarians make up a very small percentage of the relatively young countries China and India, they make the list mainly because of their large populations. However, centenarians make up a larger share of the total populations of rapidly aging Japan and Italy. Today, there are 4.8 centenarians for every 10,000 people in Japan and 4.1 in Italy. By comparison, the US is aging at about half the rate compared to Japan and Italy, partly due to its higher fertility and immigration rates. By 2050, China is expected to have the largest centenarian population, followed by Japan, the U.S., Italy, and India.
What is the main reason underlying this rapid aging of some of the most populated countries in the world?
What is the main reason underlying this rapid aging of some of the most populated countries in the world? In terms of aging of entire populations, as demonstrated by the countries listed above, the combination of decreasing birthrates and increased longevity seem to be the main factors. But in terms of the rapidly increasing number of centenarians, the answers is not so clear. Humans have obviously not changed genetically in the past 75 years which suggests that non-genetic, environmental or lifestyle factors should primarily be responsible. One of these factors has been the massive multi-trillion interventions in modern medicine and surgery which have greatly reduced mortality from infectious and age-related diseases, without reducing the number of people afflicted by most of these chronic diseases, the so-called prevalence rates. On the contrary, the prevalence of our most common chronic diseases have been increasing over the last 75 years in the US and countries around the world which have adopted sedentary lifestyles and the unhealthy Standard American Diet. In view of this chronic disease epidemic, it is highly unlikely that the increase in number of centenarians is related to the adoption of a healthier lifestyle, in particular diet, regular physical activity and social interactions.
Aging affects almost all of the body’s systems: the senses, the digestive organs, the cardiovascular system, the immune system, the bones, the muscles, and even the gut’s microbiome. Interestingly, in a healthy individual, the central nervous system—the brain and spinal cord—is among those least affected by age. In most tissues, the normal decline in function in the absence of neurodegenerative disorders like Alzheimer’s and Parkinson’s disease is not drastic, but it greatly accelerates in situations of chronic stress, unhealthy diets, and disease, as we are witnessing in the form of the unfolding chronic non-communicable disease epidemic, including accelerated cognitive decline.
Changes to bones (osteopenia) and muscles (sarcopenia) affect an older person’s daily life perhaps more than anything else. Between the ages of 30 and 60, bone density and muscle mass decrease in both men and women. In industrialized countries, between the ages of 30 and 75, about half the body’s muscle mass disappears, while the amount of fat doubles. Rather than being a normal part of aging, a major reason for this decline in musculoskeletal function is related to the predominantly sedentary lifestyle that modern societies have adopted.
The heart, blood vessels, and lungs are durable structures, built for a long lifetime. The fact that so many older people develop heart and lung problems has less to do with the aging process than with lifestyle factors, such as smoking, obesity, consuming an unhealthy diet, and lacking exercise. Many large-scale epidemiological studies are supporting this major role of lifestyle.
Several studies have explored the potential role of the gut microbiome in healthy aging. In contrast to our tissues and organs, the microbes living inside of us have their own genome, 100-fold larger than our own. As I have extensively discussed in my book, The Gut Immune Connection, current microbiome research strongly suggests potential connections to many health conditions including obesity, metabolic disorders, inflammation, cancer, and depression.
“Throughout the human life span, the gut microbiome follows some predictable temporal patterns…”
Throughout the human life span, the gut microbiome follows some predictable temporal patterns, with rapid change from infancy to age three, remarkable stability up until middle age, and then accelerated change starting in late adulthood. Previous studies have found gut microbiome pattern differences between older adults who are lean and physically active compared to their less fit and healthy contemporaries. Other research has connected early development of frailty to less gut microbial diversity.
“…older adults who had a more unique, personalized pattern of changes to their GI microbe profile with age also tended to be healthier and live longer…”
In a recent study, published in the prestigious journal Nature Metabolism, a group of prominent investigators from several US universities with lead author Tomasz Wilmanski analyzed gut microbiome genetic sequences and a wealth of other health and survival outcomes data from more than 9,000 people between the ages of 18 and 101. The investigators found that older adults who had a more unique, personalized pattern of changes to their GI microbe profile with age also tended to be healthier and live longer than peers with less microbiome divergence. According to this study, the identified microbiome pattern of healthy aging is characterized by a depletion of core taxa found across most humans, primarily the genera Bacteroides. Retaining a high Bacteroides dominance into older age, or having a low gut microbiome uniqueness measure, predicted decreased survival in a four-year follow-up.
“The loss of core groups of microbes, and the increase in α-diversity reported in long-lived individuals suggest that gut microbiomes may become increasingly unique, to each individual as they age.”
Several studies conducted on centenarian populations provided potential insight into gut microbial trajectories associated with aging. One of these demonstrated that gut microbiomes of centenarians (≤104 years of age) and supercentenarians (104+ years) show a depletion in core abundant taxa (Bacteroides, Roseburia and Faecalibacterium, among others), complemented by an increase in the prevalence of rare taxa. Similar findings have since been reported in other centenarian populations across the world, in particular in regions identified as Blue Zones, such as in Sardinian, Chinese and Korean centenarians, relative to healthy, younger controls. Some studies have also reported higher levels of gut α-diversity in centenarians compared to younger individuals, indicating that gut microbiomes continue to develop within their hosts, even in the latest decades of human life. The loss of core taxa, the exact identities of which may vary across different human populations (Bacteroides vs. Prevotella), and the increase in α-diversity reported in long-lived individuals suggest that gut microbiomes may become increasingly divergent, or unique, to each individual as they age.
“…those with less diverse gut environments used more medications and were nearly twice as likely to die during the study period.”
In the Wilmansky study, people whose gut microbiomes had grown more unique with age were able to walk faster and had better overall mobility than peers who showed less GI microbe changes with age. Plus, those with less diverse gut environments used more medications and were nearly twice as likely to die during the study period. Unsurprisingly, the research team suggested that modern diets like the Standard American Diet, rich in salty, sugary, or fatty processed foods may be responsible for the microbiome changes in less healthy individuals, may be the main factor underlying the observed age-related changes.
“…the progressive, exponential increase in centenarians in certain countries in the world, cannot simply be explained by dramatic lifestyle changes.”
In summary, a wealth of epidemiological and observational studies support the concept that our bodies and brains have evolved to last up to 100 years at high functional capacity. Obviously, not everybody reaches that goal, depending on variabilities in genes, environmental factors, lifestyle, and access to modern healthcare. Longevity occupies a certain bandwidth, within which people can die at a relatively young age, or live to 100. Where we find ourselves in this wide bandwidth depends a lot on our lifestyle choices, a conclusion supported by a wealth of scientific evidence.
The big unanswered question is why we are witnessing a progressive, exponential increase in centenarians in certain countries around the world. In developing countries this increase may in good parts be due to the benefits of modern medicine and public health measures, in the form of antibiotics, vaccinations and increased hygiene. However, the increased longevity is harder to explain in the developed world, which has been experiencing an epidemic of chronic diseases during the last 75 years, driven in large parts by negative lifestyle and environmental factors.
How can this epidemic with increased morbidity be associated with a rising number of centenarians? The answers to this question will have major implications for our future. On the other hand, in the developed world, leading a healthy lifestyle is certainly the most effective way to move to the upper limit of this bandwidth without requiring an ever-increasing number of supplements or futuristic genetic engineering.
Dr. Emeran Mayer is a Distinguished Research Professor in the Departments of Medicine, Physiology and Psychiatry at the David Geffen School of Medicine at UCLA, the Executive Director of the G. Oppenheimer Center for Neurobiology of Stress and Resilience and the Founding Director of the Goodman-Luskin Microbiome Center at UCLA.