Symposium
Acciaroli (Cilento-Salerno)
ITALY
May 21–25, 2025
C1 A 0 THE CIAO STUDY
A DECADE OF SCIENCE ON
HEALTHY AGING,
STEM CELLS AND THE REVEALED SECRETS OF LONGEVITY
OVERVIEW
The residents of Cilento, Vallo di Diano and the Alburni National Park in southern Italy are known for their remarkably long lives, robust health and low incidence of disease.
For more than a decade, researchers from Sanford Burnham Prebys, the University of California San Diego, Great Health Science and University La Sapienza in Rome have
A collaboration between Sanford Burnham Prebys, University La Sapienza, Sanford Stem Cell Institute at UC San Diego and Great Health Science
been working to understand the biological, psychological and social factors that promote their remarkable health and longevity.
Their published findings and ongoing research through the CIAO study (Cilento Initiative on Aging Outcomes) have relevance to the health and well-being of everyone.
Sponsoring Organizations Introduction
Presenting Scientists and Physicians Symposium Program
What Is Longevity Science? • What Science Understands about Aging and Living (Long and Well) • Blue Zones • What Is the Mediterranean Diet? • The CIAO Study and a Select Survey of Recent Research • Stem Cells: Biology and Therapeutic Potential
SPONSORING ORGANIZATIONS
Sanford Burnham Prebys is an independent biomedical research institute dedicated to understanding human biology and disease and advancing scientific discoveries to profoundly impact human health. For more than 49 years, our research has produced breakthroughs in cancer, neuroscience, immunology and children’s diseases, and is anchored by our NCI-designated Cancer Center and advanced drug discovery capabilities.
Visit sbpdiscovery.org
Formally known as the Università degli Studi di Roma “La Sapienza,” abbreviated simply as Sapienza (“wisdom”). It is a public research university located in Rome, Italy, founded in 1303. With 122,000 students, it is the largest university in Europe—and ranked among the world’s major education and research centers.
Visit uniroma1.it/en
Launched in 2022 with a $150 million gift from philanthropist T. Denny Sanford, the Institute is a leader in developing and delivering the therapeutic promise of human stem cells to treat, remedy or cure a vast array of conditions and diseases.
Visit stemcells.ucsd.edu
An international collaboration with public and private research organizations to promote and conduct studies and clinical trials aimed at developing new knowledge and managing patients with acute and chronic diseases, focusing particularly on healthy aging and longevity.
Visit greathealthscience.com
INTRODUCTION
The idea of aging—and resisting its effects—traces back to the earliest written records. Our desire to live very long and healthy lives is older than even our most optimistic aspirations.
Before the emergence of science, attempts to control aging, disease and death employed notions of magic and supernatural agencies. The idea of aging was gradually developed in Greek and Roman medicine and incorporated into religious beliefs and social practices, observed the late-English psychologist Dennis Basil Bromley (1925-2015) in his seminal 1966 book, “The Psychology of Human Ageing.”
Modern scientific approaches to aging did not clearly emerge until the 17th century “with systematic medical and statistical inquiries into the causes of death, and later, in the 19th and 20th centuries, into the biological mechanisms of aging.”
We’ve learned a lot about how and why humans age, from the inner workings of cells to the physical, psychological and social drivers of life expectancy.
We’ve begun to tap the extraordinary regenerative powers of stem cells, which possess two important properties. They are self-renewing, and they can become almost any kind of cell in the body. Both abilities are the foundation of regenerative medicine and represent great potential in treating not just age-related diseases, but perhaps aging itself. Still, great mysteries remain in the details: Why and how do a relatively small number of humans age more gracefully, with sustained and better health, than the rest of us?
The CIAO study represents one of the first and few coordinated, international efforts to parse the mysteries of healthy aging and longevity using the most advanced scientific tools and approaches.
The study was launched in Cilento because it is recognized by UNESCO and others as the originator of the Mediterranean diet, first described by Ancel Keys in the late 1950s.
Over the past two years, we have been using stateof-the-art techniques that push the boundaries of regenerative medicine.
Conducted by Project Lead Tatiana Kisseleva, MD, PhD, with David Brenner, MD, and Salvatore Di Somma, MD, PhD, and supported by the Sanford Stem Cell Institute at UC San Diego under the supervision of Catriona Jamies, MD, PhD, we are creating novel analyses of the genetic, epigenetic, transcriptomic, metabolic, proteomic and environmental factors that contribute to extraordinary longevity.
The goal is to identify the key factors associated with healthy aging and the mechanisms of their regulation.
We are also using induced pluripotent stem cell (iPSC) technology to generate stem cells from the
blood of centenarians to model age-related stresses in human 3D organoids. This work will provide new insights into the development of regenerative medicine strategies that promote healthy aging and also for treating age-related conditions. Preliminary collaborative research work will be presented at the meeting.
This symposium is an update on how far the collaborative sciences of healthy aging, longevity and stem cells have come and where they go next.
Within this program, you will find a listing of symposium speakers, their topics, days and times, plus background information on longevity science, aging research, Blue Zones, the Mediterranean diet, the CIAO study, stem cells, published research and further reading.
Sincerely,
Symposium President
David A. Brenner, MD
President and CEO, Sanford Burnham Prebys Donald Bren Chief Executive Chair
Symposium Chair
Salvatore Di Somma, MD, PhD Professor, University La Sapienza Rome
Scientific Board
Tatiana Kisseleva, MD, PhD Professor, UC San Diego School of Medicine
Catriona Jamieson, MD, PhD Director, Sanford Stem Cell Institute, UC San Diego
Tatiana Kisseleva, MD, PhD
Catriona Jamieson, MD, PhD
David A. Brenner, MD
Salvatore Di Somma, MD, PhD
PRESENTING SCIENTISTS AND PHYSICIANS
Corina Antal, PhD
Assistant professor, UC San Diego
Paola Antonini, MD, PhD
Great Health Science
Andreas Bergmann, PhD
Founder—SphingoTec, Adrenomed AG and 4teen4 Pharmaceuticals GmbH
David A. Brenner, MD
President and CEO, Sanford Burnham Prebys
Donald Bren Chief Executive Chair
Giovanni D’Arena, MD
Biologist; founder of Laboratory D’Arena in Vallo della Lucania (Salerno-Italy)
Antal studies the interplay between epigenetics, RNA processing and cell signaling to uncover new mechanisms underlying cancer progression.
Antonini is a highly regarded expert in clinical science, translational research and the development of innovative products encompassing cancer vaccines, biological agents for hematological and oncological conditions, autoimmune disease therapies, medical devices and radiopharmaceuticals.
Bergmann is a serial entrepreneur, having founded or co-founded more than 10 biotechnology companies. He has been a leader in the discovery and routine adoption of important blood biomarkers, as well as the development of drug candidates for critical care diseases.
Brenner is a physician-scientist, having led health sciences at several major academic institutions while being a recognized leader in the field of gastroenterology research, with more than 200 peer-reviewed publications, two patents and ranking among Highly Cited Researchers by Web of Science and Clarivate Analytics.
The D’Arena laboratory represents a center of excellence for high-quality, advanced laboratory testing and biomarkers. It is certified by the National Research Council of Italy.
Luigi Di Gregorio, MD
Surgeon and general practitioner; president of Parmenide GPs Association of Cilento region
Salvatore Di Somma, MD, PhD
Professor, University La Sapienza Rome Great Health Science
Nicola Ferrara, MD
Former professor of geriatrics, University of Naples Federico II
John Hetzel, MD
Physician, Victoria, Australia
Mohit Jain, MD, PhD
Professor, Center for Microbiome Innovation, UC San Diego
Di Gregorio coordinates all the general practitioners in Cilento for networking and data collection for research purposes, focusing on epidemiological data related to longevity and life expectancy.
Di Somma is a former professor of medicine at University La Sapienza and founder of Great Health Science, an international academic research organization focusing on healthy aging and longevity. He has published more than 300 papers on clinical internal medicine, acute cardiac care, cardiology and emergency medicine, and is co-principal Investigator of the CIAO study. He is a Stellar Scholar in the Sanford Stem Cell Fitness and Space Medicine Center, part of the Sanford Stem Cell Institute at UC San Diego.
Ferrara is the former president of the Italian Association of Geriatrics and Gerontology and is an expert in the clinical settings of healthy aging.
Hetzel works with colleagues around the world to study and compare the drivers of longevity and healthy aging.
Jain directs a multi-disciplinary research team of chemists, engineers, mathematicians, epidemiologists and physicians at UC San Diego focused on the development of next-generation mass spectrometry systems and their application for human discovery.
Catriona Jamieson, MD, PhD
Director, Sanford Stem Cell Institute, UC San Diego
Director, CIRM Alpha Clinic, UC San Diego
Sanford Stem Cell Institute Chancellor’s Endowed Chair in Regenerative Medicine
Jamieson is a leading physician-scientist in cancer stem cell biology and a specialist in myeloproliferative disorders and leukemia. Her research also explores how space alters cancer progression. Her mission is to discover life-saving therapies for cancer that tackle the root cause of the disease, and to advance therapeutics that enhance stem cell regeneration.
Alexander Khalessi, MD
Surgeon and professor, UC San Diego Health and School of Medicine
Tatiana Kisseleva, MD, PhD
Professor, UC San Diego School of Medicine
Khalessi is a board-certified neurosurgeon, chair of the Department of Neurological Surgery, the Don and Karen Cohn Chancellor’s Endowed Chair in Neurosurgery and co-director of the Brain Tumor program at the Sanford Stem Cell Institute. He specializes in complex cranial surgeries, endovascular neurosurgery, stroke care and neurological oncology; as well as basic research into tumor heterogeneity, potential therapeutic targets and treatment innovations.
Kisseleva is a trained liver surgeon who studies the origins of fibrogenic myofibroblasts (liver scarring) and identifying novel targets for anti-fibrotic therapy. She is director of the Sanford Stem Cell Fitness and Space Medicine Center, part of the Sanford Stem Cell Institute. She holds a Sanford Stem Cell Institute Endowed Chair.
Giuseppe Leonardi, MD
Cardiologist, University of Catania (Sicily)
Barbara Maiese, PhD
Psychologist
Sheldon Morris, MD, MPH
Clinical professor, UC San Diego School of Medicine
Leonardi is an expert in heart failure, the management of cardiovascular diseases, and their genetic and epigenetic aspects.
Maiese is an authority in psychological assessments behavior in elderly populations. She is also an expert in evaluations of neurological assessments of cognitive status in adults.
Sheldon studies the prevention, diagnosis, pathogenesis and treatment of infectious diseases, especially HIV and other sexually transmitted infections. He is deputy director and data management lead for the Sanford Stem Cell Clinical Center’s CIRM Alpha Clinic, which provides inpatient and outpatient cell/gene/stem cell therapies and conducts regenerative medicine clinical trials. He holds a Sanford Stem Cell Institute Endowed Chair.
Alysson Muotri, PhD
Professor, UC San Diego School of Medicine
Muotri investigates the biological complexities of the human brain, specifically the factors that fuel neuronal diversity and make human brains singular and unique. His work spans studying stem cell functions in space to how infectious diseases like the Zika virus effect the brain. He also creates brain organoids derived from the stem cells of patients with neurological diseases to study the effects of rapid aging, stress and microgravity. Muotri is director of the Sanford Integrated Space Stem Cell Orbital Research Center, part of the Sanford Stem Cell Institute, where he holds an endowed chair.
Vincenzo Pizza, MD, PhD
Neurologist, Vallo della Lucania Hospital, Salerno (Italy)
Giovanni Rizzo, MD
Physician, laboratory medicine
Silvia Ruggieri, BME
Great Health Science
Pizza is the head of the neurology department at Vallo della Lucania hospital and is an expert in cognitive disorders, especially in the elderly population of Cilento.
Rizzo is an expert in blood sampling and processing procedures for molecular biology studies based at the D’Arena laboratory in Salerno.
Ruggieri is a biomedical engineer skilled in the clinical development of medical devices, artificial intelligence software research and project management. She has expertise in data analysis, statistical methods and clinical trial coordination.
Giuseppe Scarano, MD
Physician
Scarano is director of Preventive Medicine and Health Service at Vallo della Lucania district of Salerno Community Health Service. He is an expert in the Mediterranean diet and is one of the founders of the MuSea (Museum of the Sea – Pioppi) and of the Ancel Keys Museum of Mediterranean Diet–Pioppi – Cilento region–Salerno. Scarano is also a co-principal investigator of the CIAO study.
Xiao Tian, PhD
Assistant professor, Sanford Burnham Prebys
Allen Wang, PhD
Senior associate director, Center for Epigenomics, UC San Diego
Tian investigates the fundamental mechanisms of aging and their roles in driving age-related diseases, with the goal of mitigating the effects of aging using genetic and epigenetic interventions.
Wang uses large-scale epigenomic datasets and disciplines like spatial transcriptomics, developmental biology, epigenomics and human genetics to drive epigenomics discoveries via deep and productive collaborative projects with teams of multi-disciplinary investigators.
Gene Yeo, PhD, MBA
Professor, UC San Diego School of Medicine
Yeo’s research interests are in understanding and manipulating RNA processing in development and disease using induced pluripotent stem cell and murine models. His lab is an active participant in RNA genomics technology and therapeutics development. Yeo is director of the Sanford Stem Cell Innovation Center, which focuses on developing new genomic technologies, including spatial multi-omics, to identify novel therapeutic targets in aging-related and developmental diseases. He holds an endowed chair at the Sanford Stem Cell Institute.
Su-Chun Zhang, MD, PhD
Professor, Sanford Burnham Prebys
Zhang is a stem cell science pioneer whose work has profoundly changed the understanding of how brain cells work and has led to novel approaches for repairing or replacing them in diseases like Alzheimer’s and Parkinson’s. He holds the Jeanne and Gary Herberger Leadership Chair in Neuroscience.
SYMPOSIUM PROGRAM
Thursday, May 22
CIAO study
La Pineta Hotel Beach & Spa
Acciaroli, Italy
9am–5:15pm, with lunch from 1:05–2:05pm
Chairs
David A. Brenner, MD
Salvatore Di Somma, MD, PhD
Speakers and Topics
Morning session
Time periods include final five minutes for discussion.
9am Registration
9:15–9:45am
Welcome from local officials and government representatives
9:45–10:10am
Nicola Ferrara (Italy)
Italy aging—demographic and epidemiological aspects
10:10–10:35am
Luigi Di Gregorio, MD (Italy)
Epidemiology of centenarians in Cilento; the general practitioners’ perspective
10:35–11:00am
John Hetzel, MD (Australia)
Trialing longevity health checks in a rural general family medical practice
11:00–11:25am
Salvatore Di Somma, MD, PhD (Italy)
CIAO study—a decade of scientific findings
11:25–11:50am
Paola Antonini (Italy)
New and ongoing research protocols and descriptions
11:50am–12:15pm
Silvia Ruggeri (Italy)
CIAO study update
12:15–12:40pm
Giovanni D’Arena (Italy)
Routine lab testing and analyses in centenarians
12:40–1:05pm
Giovanni Rizzo (Italy)
Laboratory data collection, processing and routine results
1:05–2:05pm Lunch
La Pineta Hotel Beach & Spa
Afternoon session
2:05–2:30pm
Vincenzo Pizza (Italy)
Neurological behavior in Cilento centenarians
2:30–2:55pm
Barbara Maiese (Italy)
Psychological assessment in Cilento centenarians
2:55–3:20pm
Giuseppe Scarano (Italy)
Nutritional value of the Mediterranean diet
3:20–3:50pm
Giuseppe Leonardi (Italy)
Genetics in non-ischemic cardiomyopathies—a new point of view
Friday, May 23
Morning session
10-10:30am
Sheldon Morris (USA)
A study designed to evaluate centenarians’ health
10:30-11am
Allen Wang (USA)
Mapping human health through cohort-scale, singlecell epigenomics
11-11:30am
Mohit Jain (USA)
Metabolomic markers of aging and longevity in the Cilento population
11:30am-12pm
David Brenner (USA)
Proteomics results from the CIAO study
Afternoon session
2:30-3pm
Catriona Jamieson (USA)
Stem cell Pathways Aging and Cancer Evolution (SPACE)
3-3:30pm
Tatiana Kisseleva (USA)
The role of senescence in aging
3:30-4pm
Corina Antal (USA)
The aging pancreas: insights into RNA processing dysregulation in pancreatic cancer. Presenting via Zoom
3:50–4:20pm
Xiao Tian (USA)
Ameliorating aging through epigenetic interventions
4:20–4:50pm
Alexander Khalessi (USA)
The operating theater as living laboratory: neurological lessons on the science of aging
4:50–5:20pm
Su-Chun Zhang (USA)
Stem Cell Model of Brain Aging
Stem cells and longevity
La Pineta Hotel Beach & Spa
Acciaroli, Italy
10am–5pm, with lunch from 1–2pm
12-12:30pm
Alysson Muotri (USA)
Space-induced neural senescence and disease modeling
12:30-1:00pm
Andreas Bergmann (Germany)
Peptidyl alpha amidating monooxygenase: A key enzyme in healthy longevity?
1-2:30pm Lunch
4-4:30pm
Gene Yeo (USA)
Aging and RNA biology. Presenting via Zoom
4:30-5pm
Closing remarks
BACKGROUND
What Is Longevity Science?
The oldest human on record is a French woman named Jeanne Calment, who lived to the age of 122 years, 164 days before passing away in 1997. Calment is the only person in history who has been verified to have reached the age of 120.14
The odds of anybody currently alive matching or exceeding Clement’s long life are almost astronomical. It’s been calculated that the probability of someone living to age 125 in any given year is less than one in 10,000. Put another way: A 125-year-old human is a once-in-a-10,000-year occurrence.
On the other hand, more people are living longer. The United Nations estimates that there are roughly 722,000 centenarians (people 100 and older) currently alive in the world. Japan has the largest centenarian population at 146,000, followed by the U.S. at 108,000 and China at 60,000.
Centenarians represent a fast-growing population. By 2054, the global centenarian population is projected to be almost four million, with close to half a million in the United States alone.
Why some people live considerably longer than others is a primary question of longevity science. It’s been proposed that lifestyle factors account for 80 percent of the reason, with genetics making up the other 20 percent. That’s a matter of ongoing debate.
But hanging on to life for a century or more isn’t nearly so appealing if those later years are darkened by disease, disability and a diminished quality of life. The more pertinent goal—at least for most people—is how to live longer well.
Jeanne Calment at age 20 in 1895
What Science Understands about Aging and Living (Long and Well)
After decades of average life expectancies rising around the world due to medical and technological advancements (everything from water sanitation to antibiotics), new research suggests that humans may be reaching peak life span.
In some places, life expectancy increases have slowed, stalled or declined. A baby born in the United States in 2021, for example, had almost a one-year drop in life expectancy. A baby born one year earlier has a 1.8-year drop. That two-year decline in life expectancy is the biggest since 1921–23, almost 100 years earlier.
Today, the Centers for Disease Control says average life expectancy in the United States is 77.5 years (74.8 for males, 80.2 for females). The main driver in the recent decline was the COVID pandemic, with other factors like accidents and unintentional injuries (primarily drug overdoses) also playing roles.
behaviors that will “cure” it. We grow old because all vertebrate animal species have a natural life span defined by their gene sets and, more broadly, the inexorable biology of senescence.
Some of the most recent research suggests that for the vast majority of humans, life expectancy is pretty much what it is now: approximately 87 years (84 for men, 90 for women). It’s obviously higher in some places, lower in others.
The idea that aging can be prevented, stopped or reversed is, in fact, a timeless grift. Claims that new discoveries or technologies will allow humans to routinely live to 120 years or longer are unprovable. We would all first have to live that long.
Aging is not a disease, at least in its most universal definition. There are no potions, pills, remedies or
Debate will no doubt continue about whether there is maximum human life span, and if we’ve reached it. The science of healthy aging, however, offers much greater and livelier hope and opportunity.
Obesity, cancer and cardiovascular disease are all strongly linked to lifestyle and behavior choices. So,
too, is the rising calamity of chronic disease: More than half of U.S. adults have at least one of 10 common chronic conditions: arthritis, cancer, chronic obstructive pulmonary disease, coronary heart disease, asthma, diabetes, hepatitis, hypertension, stroke and weak or failing kidneys. One in four U.S. adults have multiple chronic conditions.
Other public health threats, like the global scourge of loneliness,5 further harm our overall health and
Blue Zones
In recent years, the concept of “blue zones” has garnered widespread popular attention. These are geographical regions where residents consistently live to be 100 years old.
Regions considered to be blue zones are Okinawa, Japan; Sardinia, Italy; the Nicoya peninsula in Costa Rica; Ikaria, a Greek island; and Loma Linda, California. (The term blue zone comes from the blue pen used by researchers to mark these areas on a map.)
Using epidemiological data, statistics, birth certificates and other research,4 blue zone advocates say they’ve identified several common characteristics of long-living inhabitants. Among them:
• They are physically active.
• They have a purpose in life.
• They avoid or manage stress.
• They eat in moderation, with a diet that is mostly plant-based.
• They consume little or no alcohol.
• They enjoy rich social lives.
well-being—and shorten our lives.
As a result, most serious longevity research and related endeavors focus on discovering or parsing biological and social factors that promote health, and thus presumably a longer, healthier life.
Given its similarities to the five designated blue zones, Cilento has been proposed as a sixth.13 But the blue zone concept remains controversial, in part because there is a dearth of uniform, well-documented, empirical evidence, such as solid data on life expectancy and health in all of these locations. Muddying the issue are commercial or non-science efforts to promote blue zone projects and products.
Projects like the CIAO study and others represent an effort to apply mainstream scientific principles and methods to the blue zone concept and find, if it exists, acceptable, measurable and reproducible markers of its effects on longevity and health.
What is the Mediterranean Diet?
The Cilento region of southern Italy is generally considered by scientists to be the cradle of the Mediterranean diet, though there are many versions. It is more of an eating pattern than a strictly regimented diet plan.12
The diet is primarily plant-based, with daily consumption of whole grains, olive oil, fruits, vegetables, beans and other legumes, nuts, herbs and spices. Animal proteins are eaten in smaller quantities, with the preference being fish and seafood.
The emphasis is on healthy fats, such as olive oil, or fats found in avocados, nuts and oily fish like salmon and sardines. Other proteins, such as poultry and dairy, are eaten in smaller quantities and less frequency; red meat is limited to a few times per month.
Water is the primary daily beverage, with moderate intake of wine with meals (one to two glasses for men, one glass for women).
Daily physical activity is stressed.
The CIAO Study and a Select Survey of Recent Research
In the 1950s, American physiologist Ancel Keys (who also had a doctorate in biology from the Scripps Institution of Oceanography) took note that the residents of a small Italian coastal town called Acciaroli seemed to enjoy remarkably long and healthy lives. The reason, Keys hypothesized, was at least partly due to their distinctly local diet.
Keys, who earlier in his career had famously (or notoriously) invented the K ration that fed U.S. soldiers during World War II, argued that there was a link between dietary cholesterol and heart disease.
In 1958, he launched his landmark Seven Country Study to study the influence of diet on health. In the decades since, the ongoing research has produced many follow-up and related studies.
Acciaroli is located on the Cilento coast of western
Italy in the Campania region. The noted longevity of its residents is broadly shared in the region, making it the focus of much scientific study on human aging and health.
In 2016, a group of scientists from UC San Diego School of Medicine and the University of Rome La Sapienza launched the CIAO (Cilento on Aging Outcomes) study. The purpose was to better understand how people can live longer and in better health by focusing over time on 300 residents, all over 100 years old, living in Acciaroli.
That same year, scientists reported initial findings from a pilot study that found that the organs and muscles of some centenarians were as efficient as those three decades younger. Specifically, they possessed low blood levels of the peptide hormone adrenomedullin, suggesting a well-functioning endothelial and microcirculatory system that provides plenty of oxygen and nutrients to organs and muscles.
Ancel Keys
A deeper look at 29 nonagenarians and centenarians found that while they experienced worse physical health than younger persons, their mental well-being was considerably better. Specifically, they were characterized by “a balance between acceptance of and grit to overcome adversities, along
lence of clinical cardiovascular disease. And even among those with structural heart abnormalities, symptoms were low.16
While all of the participants studied adhered to the Mediterranean diet, researchers proposed that NCs may practice optimal adherence and benefit from other lifestyle factors, such as regular, rigorous exercise and positive personality traits.
with a positive attitude and close ties to family, religion, and land, providing purpose in life.”8
Those early findings were followed in 2020 by a fuller descriptive, cross-sectional analysis of 29 super-elderly residents participating in the study (persons 90 years and older), comparing them to 49 younger co-inhabitants, ages 50–75.1
Notably, none of the nonagenarians and centenarians (NCs) exhibited severe cognitive impairment, and there was an extremely low incidence of dementia. The majority of the NCs lived autonomous daily lives and enjoyed good physical health.
A different pilot study found that NCs in Cilento enjoyed healthy metabolic profiles and a low preva-
Researchers have also compared middle-aged populations in Cilento with Malmö, a city in Sweden, for prevalence of cardiovascular disease (CVD) and cancer. Both prevalence rates were similar even though Cilento residents have more risk factors. When those are accounted for, the CVD prevalence rate is half that of Malmö. As for cancer, the prevalence rate was about one-third compared to Malmö.15
In 2020, after studying middle-aged and older adults in San Diego and Cilento, researchers found that the complex personality trait of wisdom may be a protective factor against loneliness.2
In 2021, researchers looked at whether the Mediterranean diet in Cilento was linked to both longevity and potential prevention of prostate cancer. The findings were inconclusive, but the authors said they merited further investigation.9
Stem Cells: Biology and Therapeutic Potential
Stem cells are a special type of cell with two important properties: They are able to make more cells like themselves (self-renew), and they can become other types of cells that do other things (differentiation). Depending on where the stem cells are located, they can become any of the cell types that function in blood or cells in the brain, heart muscle, liver, spleen or bone.
Stem cells are found in almost all tissues of the body, and are critical to the maintenance and repair of tissues. Embryonic stem cells are the most versatile since they can develop into all the cells of the developing fetus. The majority of stem cells in the body have fewer abilities to give rise to repair the
tissues and organs in which they reside.
Science has learned how to create induced pluripotent stem cells (iPSCs) in culture. In other words, to create stem cells outside the body and then induce them to become the cell type needed. As a result, iPSCs have become the foundation of regenerative medicine, as well as the idea that stem cell therapies can be used to regenerate and repair tissues that have been damaged or affected by disease, from cancers to dementia.6
That ability alone, already being shown in numerous current and experimental therapies, can dramatically impact human longevity by addressing age-related diseases. There is hope, however, that as stem cell therapies advance, they may become part of strategies to counter aging itself.7
PUBLISHED RESEARCH
1Pizza V, Antonini P, Marino R, D’Arena G, Lucibello SG, Rizzo M, Brenner DA, Jeste DV, Somma SD. Cognitive Health of Nonagenarians in Southern Italy: A Descriptive Analysis from a Cross-Sectional, Home-Based Pilot Study of Exceptional Longevity (Cilento Initiative on Aging Outcomes Or CIAO). Medicina (Kaunas). 2020 May 5;56(5):218. https://doi:10.3390/medicina56050218.
2Jeste, D. V., Di Somma, S., Lee, E. E., Nguyen, T. T., Scalcione, M., Biaggi, A., … Brenner, D. (2020). Study of loneliness and wisdom in 482 middle-aged and oldest-old adults: a comparison between people in Cilento, Italy and San Diego, USA. Aging & Mental Health, 25(11), 2149–2159. https://doi.org/10.1080/13607863.202 0.1821170
3Aliberti, S.M.; Donato, A.; Funk, R.H.W.; Capunzo, M. A Narrative Review Exploring the Similarities between Cilento and the Already Defined “Blue Zones” in Terms of Environment, Nutrition, and Lifestyle: Can Cilento Be Considered an Undefined “Blue Zone”? Nutrients 2024, 16, 729. https://doi.org/10.3390/nu16050729
4Buettner D, Skemp S. Blue Zones: Lessons From the World’s Longest Lived. Am J Lifestyle Med. 2016 Jul 7;10(5):318-321. doi: 10.1177/1559827616637066. PMID: 30202288; PMCID: PMC6125071.
5H.O., Cudjoe, T.K., Bu, F. et al. The state of loneliness and social isolation research: current knowledge and future directions. BMC Public Health 23, 1049 (2023). https://doi.org/10.1186/s12889-023-15967-3
6Zakrzewski W, Dobrzynski M, Szymonowicz M, Rybak Z. Stem cells: past, present, and future. Stem Cell Res Ther. 2019 Feb 26;10(1):68. https://doi: 10.1186/s13287-019-1165-5.
7Brunet, A., Goodell, M.A. & Rando, T.A. Ageing and rejuvenation of tissue stem cells and their niches. Nat Rev Mol Cell Biol 24, 45–62 (2023). https://doi.org/10.1038/s41580-022-00510-w
8Anna Scelzo, Salvatore Di Somma, Paola Antonini, Lori P. Montross, Nicholas Schork, David Brenner, Dilip V. Jeste. Mixed-methods quantitative–qualitative study of 29 nonagenarians and centenarians in rural Southern Italy: focus on positive psychological traits. International Psychogeriatrics. Volume 30, Issue 1. 2018. Pages 31-38. ISSN 1041-6102. https://doi.org/10.1017/S1041610217002721.
9Ferro M, Lucarelli G, Buonerba C, Terracciano D, Boccia G, Cerullo G, Cosimato V. Narrative review of Mediterranean diet in Cilento: longevity and potential prevention for prostate cancer. Ther Adv Urol. 2021 Jul 22;13:17562872211026404. https://doi:10.1177/17562872211026404.
10Aliberti SM, De Caro F, Funk RHW, Schiavo L, Gonnella J, Boccia G, Capunzo M. Extreme Longevity: Analysis of the Direct or Indirect Influence of Environmental Factors on Old, Nonagenarians, and Centenarians in Cilento, Italy. Int J Environ Res Public Health. 2022 Jan 30;19(3):1589. https://doi: 10.3390/ ijerph19031589. PMID: 35162611; PMCID: PMC8834812.
11Aliberti SM, Funk RHW, Ciaglia E, Gonnella J, Giudice A, Vecchione C, Puca AA, Capunzo M. Old, Nonagenarians, and Centenarians in Cilento, Italy and the Association of Lifespan with the Level of Some Physicochemical Elements in Tap Drinking Water. Nutrients. 2023 Jan 1;15(1):218. https://doi:10.3390/nu15010218.
12Bifulco, M., Pisanti, S. The mystery of longevity in Cilento: a mix of a good dose of genetic predisposition and a balanced diet based on the Mediterranean model. Eur J Clin Nutr 71, 1020–1021 (2017). https://doi. org/10.1038/ejcn.2017.91.
13Aliberti SM, Donato A, Funk RHW, Capunzo M. A Narrative Review Exploring the Similarities between Cilento and the Already Defined “Blue Zones” in Terms of Environment, Nutrition, and Lifestyle: Can Cilento Be Considered an Undefined “Blue Zone”? Nutrients. 2024 Mar 2;16(5):729. doi: 10.3390/nu16050729. PMID: 38474857; PMCID: PMC10934765.
14Robin-Champigneul F. Jeanne Calment’s Unique 122-Year Life Span: Facts and Factors; Longevity History in Her Genealogical Tree. Rejuvenation Res. 2020 Feb;23(1):19-47. doi: 10.1089/rej.2019.2298. PMID: 31928146.
15Melander O, Antonini P, Ottosson F, Brunkwall L, Gallo W, Nilsson PM, Orho-Melander M, Pacente G, D’Arena G, Di Somma S. Comparison of cardiovascular disease and cancer prevalence between Mediterranean and north European middle-aged populations (The Cilento on Ageing Outcomes Study and The Malmö Offspring Study). Intern Emerg Med. 2021 Sep;16(6):1567-1572. doi: 10.1007/s11739-020-02625-4. Epub 2021 Jan 30. PMID: 33515187; PMCID: PMC8354896.
16Smith E, Ottosson F, Ericson U, Hellstrand S, Rizzo M, Sukruang K, Pizza V, Orho-Melander M, Nilsson PM, Kennbäck C, Fernandez C, Antonini P, Di Somma S, Melander O. Impact of a short-term Mediterranean diet intervention on plasma metabolites: a pilot study. Metabolomics. 2024 Jul 27;20(4):82. doi:10.1007/s11306-024-02154-7. PMID: 39066903; PMCID: PMC11283393.
17Daniels LB, Antonini P, Marino R, Rizzo M, Navarin S, Lucibello SG, Maisel AS, Pizza V, Brenner DA, Jeste DV, Di Somma S. Cardiovascular health of nonagenarians in southern Italy: a cross-sectional, home-based pilot study of longevity. J Cardiovasc Med (Hagerstown). 2020 Feb;21(2):89-98. doi: 10.2459/ JCM.0000000000000910. PMID: 31789688.
ADDITIONAL READING
“Biomarker lifts a secret of old age.” European Biotechnology Life Science and Industry magazine. May 9, 2016.
“Good microcirculation indicates increased lifespan.” Sphingotec. September 5, 2016.
“Rosemary and Time: Does This Italian Hamlet Have a Recipe for Long Life?” Bryant Rousseau. The New York Times. October 19, 2016.
“Mediterranean Diet: The Right Way to Longevity?” Walter Milano, Vincenzo Pizza, Anna Capasso. Annals of Nutrition & Food Science. February 20, 2018.
“How Long Can We Live? The Limit Hasn’t Been Reached, Study Finds”
The mortality rate flattens among the oldest of the old, a study of elderly Italians concludes, suggesting that the oldest humans have not yet reached the limits of life span. Carl Zimmer. The New York Times. June 28, 2018.
“A Visit to the Land of Happy Old People: Reflections on the Mediterranean diet as an antidote to encroaching middle age.” Nina Burleigh. Medium. June 4, 2019.
“People in the world’s ‘blue zones’ live longer—their diet could hold the key to why.” Justin Roberts, Joseph Lillis, Mart Cortnage. The Conversation. January 24, 2024.
“Life 101: Lessons from Nicolina.” Sanford Burnham Prebys. June 18, 2024.
“Opinion: There’s a secret to living long and healthy. Just follow this. Stay away from the American diet.” David Brenner, MD. San Diego Union-Tribune. June 30, 2024.
“Have We Reached Peak Human Life Span? After decades of rising life expectancy, the increases appear to be slowing. A new study calls into question how long even the healthiest of populations can live.” Dana G. Smith. The New York Times. October 7, 2024.
“Research in Context: Can we slow aging?” NIH Research Matters. October 15, 2024.
“Do People in ‘Blue Zones’ Actually Live Longer? The premise is catchy, but some think it’s based on faulty data.” Dana G. Smith. The New York Times. October 24, 2024.
“Shades of Blue: Blue zones, supposed havens of longevity, have become a global brand. But skeptics think they rest on shaky science.” Igancio Amigo. Science. November 21, 2024.
“What’s the secret to living to 100? Centenarian stem cells could offer clues. A bank of cells from people more than 100 years old gives scientists a new resource for studying longevity.” Smriti Mallapaty. Nature. November 29, 2024.
“What Matters More for Longevity: Genes or Lifestyle? It depends on what your goal is.” Dana G. Smith. The New York Times. January 8, 2025.
“The secret to life as a super-ager.” Matt Villano. BrainWise.
INSTITUTIONAL CONTACTS FOR MEDIA
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Great Health Science greathealthscience.com
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External Communications valeria.albini@greatnetwork.org
Sanford Stem Cell Institute (UC San Diego) stemcells.ucsd.edu
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