“In the end, it's not the years in your life that count. It's the life in your years.”
Elie Metchnikoff, Ukrainian scientist, father of cellular immunology, founder of the field
of gerontology, Nobel laureate
“The study of geriatrics begins in pediatrics.”
Ignatz Leo Nascher, Austrian-American physician, founder of the field of geriatrics
When I embarked on my infectious diseases career at an academic health center in 1977, it seemed obvious that people with compromised immunity—organ and bone marrow transplant recipients, cancer patients with very low blood neutrophil counts, and people receiving drugs that suppressed the function of their white blood cells—were the greatest risk group for contracting many, if not most, severe infectious diseases. Following my move to an inner city general hospital in 1984, I soon realized, however, that the “silver tsunami”—a metaphor for the growing number of older people in the world—was creating an even larger group of immunocompromised adults.
In this Germ Gems post, I provide a brief history of foundational leaders in the field of research on aging and highlight some of the most interesting research now being done on improving the quality as well as quantity of one’s years.
Geriatrics, gerontology, and geroscience: what’s the difference? In 1903, Ukrainian biologist Elie Metchnikoff coined the term “gerontology” to describe the systematic study of aging. While Metchnikoff is best known for and received the 1908 Nobel Prize for his landmark studies of cellular immunity, he devoted many of his later years to unraveling the influence of the gut microbiome on aging.
Also working in the early 20th century, Ignatz Leo Nascher, an Austrian-born physician practicing in New York City, coined the term “geriatrics” to describe the medical care of the elderly. He intended the term to parallel that of “pediatrics.” In so doing, he was the first to understand the similarity between very young humans, i.e., neonates, whose immune systems are immature, and very old humans with immune systems that function like that of neonates. Indeed, these two extremes of age are the greatest periods of risk of serious outcomes of most infections.
Roy Walford was another physician who played an important role in research on the immunology of aging. In his 1969 book The Immunologic Theory of Aging, Walford coined the term “immunosenescence.” According to Walford, immunosenescence involves destruction and remodeling of immune organs, dysfunction of the innate and adaptive immune systems, poor vaccination outcomes, and increased susceptibility to certain infections and malignancies.
In 2005, researchers at the Buck Institute for Aging coined the term “geroscience” to describe the science of the biological mechanisms of aging and age-related diseases. The so-called “Geroscience hypothesis” suggests that addressing aging physiology directly could help prevent or reduce the severity of chronic diseases. Geroscience is a multidisciplinary field, including molecular biology, neuroscience, genetics, and endocrinology.
In 2007, the National Institutes of Health adopted the term “geroscience” and established the first Interdisciplinary Center on Geroscience. Many investigators at American universities are now actively engaged in geroscience research.
Aging and susceptibility to infectious diseases. In my role as a medical educator, I often made the case that if you were limited to knowing only one thing about an infected patient in making a diagnosis or prognosis it would be their age. Why? Because age profoundly shapes both the susceptibility to and the severity of virtually all infectious diseases. I have described the profound impact of age on the pathogenesis of infectious diseases in many of my previous Germ Gems posts. Two notable examples are viral infections: SARS-CoV-2 (See “COVID-19: What’s Age Got To Do With It?,” February 11, 2022) and Respiratory Syncytial Virus (See “Respiratory Syncytial Virus: A Little Known Virus with a Big Impact,” October 5, 2022).
Historically, most attention to the biological consequences of aging focused on older adults, that is, people 60 years of age or older. Recent studies, however, suggest that our bodies may undergo a dramatic wave of age-related molecular changes not only in our 60s but also in our mid-40s (See “Why Aging Comes in Dramatic Waves in Our 40s and 60s,” Scientific American, August 27, 2024).
Life expectancy, longevity, and lifespan. Life expectancy is the average number of years a person is expected to live. It is influenced by many factors, including gender, race, income level, and access to health care. The life expectancy in the U.S. was 47 years in 1900 and is 79.5 years now.
For most of the 20th and 21st centuries, life expectancy was on a steady rise; then it dropped to just over 76 in 2021—the largest decrease over a two-year span since the 1920s. World War I and the influenza A pandemic were responsible for the downturn of life expectancy in the 1920s; the opioid epidemic and COVID-19 were behind the recent fall in life expectancy. Fortunately, the COVID-19 Public Health Emergency ended in 2023, and life expectancy is again increasing.
Lifespan is the maximum number of years a person can live. Jeanne Calmette, a French woman, lived to the age of 122 years thereby setting the human lifespan at 122 years. Longevity is the ability to live longer than the average lifespan for a species.
Over the years many researchers, including most recently geroscientists, have been searching for modalities to extend the healthy human lifespan. As an example, in a March 2024 report in New Scientist, “Antibody therapy makes the immune system of old mice young again,” researchers reported that antibodies that depleted aberrant blood stem cells resulted in significantly extending the lives of the treated mice. The relevance of these studies to humans is unknown, but as one of the researchers pointed out, “By rejuvenating or improving immune function in older people, that could really help with fighting off infections.”
Metformin is an agent that looks especially promising to me for improving immune function to help fight off infections. Metformin is a Food and Drug Administration-approved first-line drug for treating type 2 diabetes. It has been used for over 60 years. It is safe, effective, and inexpensive. And, “[b]eyond its antihyperglycemic effect, metformin can exert multiple antiaging effects at the cellular and organism levels, which are closely associated with improvements in aging hallmarks such as inflammation, autophagy and cellular senescence.” (See “Metformin’s Mechanisms in Attenuating Hallmarks of Aging and Age-Related Disease,” Aging and Disease, Vol. 13, 2022).
What have centenarians taught us? Centenarians—people who live to 100 years or older—are a group of long-lived humans that has captured the attention of many researchers. Several research groups, including investigators at Boston University School of Medicine and Tufts University, have reported that centenarians possess unique (“elite”) immunity that helps them achieve exceptional longevity and provides the capacity to successfully fight off and recover from infections. From these studies, it is hoped that both genetic and behavioral factors can be identified that allow everyone to live a healthy lifespan.
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