Symposium
Acciaroli (Cilento-Salerno)
ITALY
May 21–25, 2025
Acciaroli (Cilento-Salerno)
ITALY
May 21–25, 2025
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.
On behalf of organizers and participants, a special note of gratitude and appreciation to T. Denny Sanford for his enduring support and generosity in the study of human longevity, which have helped make the CIAO study and this symposium possible.
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/pagina-strutturale/home
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
In late May 2025, researchers from around the world gathered in Acciaroli on the coast of the Cilento-Salerno region of central Italy.
The town is tiny but of particular global interest: Its citizens and those of the many villages in the region are particularly long-lived — 100 years and older, but still remarkably healthy.
For a decade, scientists participating in the Cilento Initiative on Aging Outcomes or CIAO study have studied, interviewed, measured and monitored the centenarians of Cilento, seeking to better understand the secrets to their longevity and healthy lives.
The gathering in May was a unified effort to review more than 10 years’ worth of studies, data and findings, to understand what has been learned and plan for next steps. This document contains content from the original program, plus the news releases issued before and after to media around the world.
– Tatiana Kisseleva, MD, PhD
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
One-hundred-and-one-year-old resident Nicolina (center) of Cilento, Italy with CIAO study researchers. Credit: Sanford Burnham Prebys
It’s notable when a scientific study reaches the decade mark, but when the topic is the healthy aging of people who have lived 10 times as long, it just means there’s still a lot more to learn.
This month, researchers participating in the Cilento Initiative on Aging Outcomes or CIAO study will gather in Acciaroli (Pollica-Cilento) Salerno, Italy to review a decade of work and plan their next steps.
Launched in 2016, the CIAO study seeks to identify key factors (biological, psychological and social) that promote healthy aging and extreme longevity.
The Natural Park of Cilento region in southern Italy is home to roughly 300 residents who are more than100 years old and in robust health. The broader region is notable for the long lives of its residents. It was the original source of research for Ancel Keys, the American physiologist who studied the influence of diet on health and first promoted the benefits of the Mediterranean diet.
Scientists hope to reveal the longevity secrets of the Cilento region using an array of tools to measure metabolomics, biomes, cognitive dysfunction and protein biomarkers for risk of heart disease, Alzheimer’s, kidney disease and cancer, along with psychological, social and lifestyle surveys.
“There is no single secret to living a long, healthy life,” said Salvatore DI Somma, MD, the study’s lead Italian investigator, founder of Great Health Science and symposium co-chair. “It is many secrets, most of which we are only beginning to understand and more importantly, learn how they might be applied to the well-being of everybody. The remarkable centenarians in our study are leading the way.”
The CIAO study is a multi-institution collaboration that includes Sanford Burnham Prebys, an independent, nonprofit biomedical research institute in San Diego, the Sanford Stem Cell Institute at University of California San Diego, University La Sapienza in Rome and Great Health Science, a network of public and private research organizations based in Rome, Italy.
The May 22-23 symposium, officially called the “CIAO Study: A decade of science on healthy aging, stem cells and the revealed secrets of longevity,” will feature a series of scientists and physicians describing their work and findings, from general demographic and epidemiological aspects to deeper dives into brain cell aging, the regenerative powers of stem cells and RNA biology.
“Understanding how we age and how we might age better is a timeless pursuit,” said David Brenner, MD, president and CEO of Sanford Burnham Prebys and co-chair of the symposium. “Ten years in, with the benefit of new and emerging technologies and global collaborations, we’ve come a long way. It’s important to look at where we are now and
what our key questions and steps will be in the next 10 years.”
One current CIAO project leverages genetic, epigenetic, transcriptomic, metabolic, proteomic and environmental analyses to identify key contributors to extreme longevity. Supported by the Sanford Stem Cell Institute at UC San Diego, researchers are using induced pluripotent stem cell (iPSC) derived from the centenarians to model age-related and metabolic stresses in human 3D organoids.
“This study will provide new insights into the development of regenerative medicine strategies for promoting healthy aging and treating age-related conditions,” said Tatiana Kisseleva, MD, PhD, professor of surgery at UC San Diego School of Medicine and director of the Sanford Stem Cell Fitness and Space Medicine Center. Preliminary findings are expected to be presented at the symposium.
The CIAO study has already generated multiple published papers and intriguing findings. Among them:
• In a 2016 presentation, researchers reported that the oldest residents participating in the CIAO study exhibited robust microcirculation of blood comparable in efficiency to people 30 years younger. They also noted that low blood levels of the peptide hormone adrenomedullin were an indicator for good microcirculation.
• In 2018, using a mix of scales to measure mental and physical well-being, resilience, optimism, anxiety, depression and perceived stress, researchers assessed 29 nonagenarians and 51 family members between the ages of 51 and 75.
• They found the study participants aged 90 and older had worse physical health but better mental well-being than their younger coun-
terparts. Exceptional longevity was characterized by a balance between acceptance of and grit to overcome adversities, along with a positive attitude and close ties to family, religion and the land, providing purpose in life.
• In 2020, a cross-sectional sampling of nonagenarians and centenarians, along with younger co-inhabitants from Cilento, evaluated key lifestyle, medical, echocardiographic and electrocardiographic features to identify the cardiovascular profile and lifetstyle factors associated with longevity.
• In contrast to their younger co-inhabitants, the older group did not smoke, had lower fasting glucose levels and lower LDL cholesterol despite being half as likely to be taking statins. They were physically active and enjoyed comparatively low levels of cardiovascular disease — even persons with structural heart abnormalities experienced fewer symptoms.
• Also in 2020, researchers sought to define the neurocognitive profiles of 29 residents of the Cilento region at least 90 years old and 49 younger residents ages 50 to 75 years. They found that the older cohort appeared to enjoy cognitive status comparable to their younger cohabitants without significant differences in oxidative stress markers or the APOE genotype — a genetic variation that determines a person’s risk for developing certain diseases, particularly Alzheimer’s. The authors concluded that the results might be related to the older group’s optimal adherence to the Mediterranean diet, though other lifestyle factors and positive personality traits might be contributing to their healthy aging.
tween loneliness and wisdom compared different age cohorts in San Diego and Cilento, using two validated loneliness scales. They found no significant differences in levels of loneliness among the groups, but a strong inverse correlation between loneliness and wisdom in all groups. Loneliness worsened general health, sleep quality and feelings of happiness, while wisdom improved these measures.
• La Repubblica newspaper (Italy)
• The Daily Telegraph (England)
• Brief (US)
• EurekAlert (US)
• ScienMag (US)
• Newswise (US)
• Science Daily (US)
• World News Today (US)
• WDC TV News (US)
• Press-News.org (US)
• Bioengineer.org (US)
• News Medical-Life Sciences (US)
• Today News (US)
• Researchers investigating the relationship be-
3, 2025
On May 22-23, a select group of scientists from around the world gathered in the small town of Acciaroli in the Cilento-Salerno region of Italy to review a decade’s worth of research in the ongoing Cilento Initiative on Aging Outcomes (CIAO), a longitudinal study of local residents 100 years and older.
(The CIAO study is a multi-institution collaboration that includes Sanford Burnham Prebys, an independent, nonprofit biomedical research institute in San Diego, the Sanford Stem Cell Institute at University of California San Diego, University La Sapienza in Rome and Great Health Science, a network of public and private research organizations based in Rome, Italy.)
“The centenarians of the CIAO study are remarkably robust and healthy, and can be found here in numbers per capital greater than most places on Earth,”
said Salvatore DI Somma, MD, the study’s lead Italian investigator, founder of Great Health Science and co-chair of the recently concluded symposium. “Some aspects responsible for their long and healthy aging seem apparent, but beneath them lie the deeper elements of genetics, epigenomics, metabolomics and other new bio-analytical tools and assessments. Our goal when we began the CIAO study back in 2015 — and our continuing mission — is to more precisely define the underlying drivers of a long, healthy life and to use those discoveries to help the rest of us also live longer, healthier lives, in part by slowing or preventing diseases related to aging.”
Two major components of why the centenarians of Cilento live longer and better was reaffirmed in multiple studies: Diet and lifestyle.
Ninety percent of the centenarians in the CIAO study adhere to the Mediterranean diet, which is rich in fresh fruits, vegetables, whole grains, legumes, nuts and olive oil, with minimal red meat consumption.
“The Mediterranean diet is not a meal plan. It’s not a fad,” said di Somma. “It’s a way of life.”
The diet appears to pay health dividends, both shortand long-term. In one study, researchers reported that after just six days after shifting from a northern European diet to a Mediterranean diet. metabolites (substances produced during metabolism) linked to a decreased risk of future type 2 diabetes and coronary artery disease increased significantly while biomarkers associated with red meat consumption (a risk factor for multiple diseases) declined.
A related analysis of olive oil produced in the Cilento region and widely consumed by its residents found it to be low in fatty acids and compounds associated with increased risk of heart disease or accelerated
brain decline.
Additionally, most centenarians were physically active on a regular basis and socially engaged with friends and family.
“Despite their advanced chronological age, many Cilento centenarians maintain cognitive integrity, emotional stability and adaptive neurological function,” said Paola Antonini, MD, PhD, chief medical and scientific officer at Great Health Science.
“They exhibit notable resilience against age-related neurodegenerative conditions, including Alzheimer’s, Parkinson’s and cerebrovascular disorders. Psychologically, they are emotionally resilient and stable. They use optimism as a coping strategy. They have low levels of neuroticism, but a strong sense of purpose and sustained social/family engagement.”
Recent CIAO research findings are further parsing the underlying biological mechanisms. The goal is to apply the most advanced techniques in biomedical research to study the centenarians, which include single nuclear multi-omics, metabolomics, proteomics, biomarkers, and cytokine measurements.
The epigenome is the multitude of chemical compounds that tell the genome (complete set of DNA in genes) what to do. As we age, progressive epigenetic alterations disrupt gene expression programs, compromise cell identity and impair genomic stability — all contributing to chronic inflammation, reduced regenerative potential and cell senescence, a state in which a cell permanently enters a zombie-like state: It no longer divides, but remains
metabolically active and can release inflammatory factors that contribute to age-related diseases.
“Epigenomically, no two individuals are alike, no epigenome is the same,” said Allen Wang, PhD, senior associate director at UC San Diego’s Center for Epigenomics. “That, along with the actual complexity of disease, complicates the search for therapeutic biomarkers.”
Nonetheless, Wang said rapidly developing tools like single nucleus multi-omic profiling of blood samples, which allows researchers to simultaneously analyze several aspects of individual cell nuclei (RNA, DNA, etc.) is providing clues.
For example, in single-cell epigenomic analyses of 36 Cilento centenarians, researchers found that their T-cells, part of the body’s response to infection and disease, exhibited notably coordinated immune activation and cytokine regulation. Cytokines are small proteins that act as critical chemical messengers, primarily within the immune system.
The centenarians also showed elevated antiviral and inflammatory programs, and greater communication among immune response cells.
Researchers surveyed metabolites associated with centenarians and cardiometabolic disease, a cluster of conditions that increase the risk for developing cardiovascular disease or metabolic disorders like type 2 diabetes.
and treatments, and help identify drug targets for personalized medicine.
CIAO study scientists assessed 128 centenarians and 50 controls. They found that 2,812 of the 32,514 metabolites measured differed significantly in centenarians, either in higher or lower levels. Of those 2,812 metabolites, 1,540 were significantly associated with cardiometabolic disease and 268 were deemed potentially protective against cardiometabolic disease.
Using proprietary artificial intelligence and multi-omics tools developed by Sapient, a San Diego-based biotechnology company founded by UC San Diego professor of medicine and pharmacology Mohit Jain, MD, PhD, the researchers then determined the biological age of study participants based on 24 key blood metabolite measurements.
Based on those blood samples, the majority of centenarians were biologically younger than their chronological age by an average of 8.3 years. Controls, who are also from Cilento, also appeared biologically younger, but the difference was not as pronounced.
Contrarily, the researchers found that inflammatory markers in centenarians were elevated. Chronic or excessive inflammation can be a risk factor for heart disease, autoimmune disorders and cancer.
Metabolites have various functions, including fuel, structure, signaling and acting as catalysts for chemical reactions. They can also serve as biomarkers for different diseases, improving both diagnoses
“Our initial hypothesis was that centenarians have increased inflammatory mediators, which are expected to increase with aging,” said David Brenner, MD, president and CEO of Sanford Burnham Prebys and a CIAO study principal investigator. “However, the centenarians also have increased anti-inflammatory mediators which may protect the centenarians from inflammation and tissue injury.”
Past studies with Cilento centenarians have shown they enjoy robust microcirculation of blood comparable in efficiency to people 30 years younger. The findings also indicate low blood levels of adrenomedullin (bio-ADM), a peptide hormone that regulates blood pressure, maintains vascular integrity and may have potential protective actions in various diseases.
Low levels of bio-ADM is considered an indicator of good vascular microcirculation, and good microcirculation is an indicator for increased longevity. Andreas Bergmann, PhD, chief scientific advisor for SphingoTec, a Germany-based company that develops biomarkers, and colleagues have gone further to identify an enzyme called dipeptidyl alpha amidating monooxygenase or PAM, which potentially can be used to restore bio-ADM to healthy levels and serve as a biomarker for impaired peptide activation.
In mouse studies, therapeutic application of PAM substantially restored vascular leakage at the bloodbrain barrier and improved cerebral brain flow in an animal stroke model.
In related research, researchers found that study participants in northern Europe and in the Cilento region who focused on a Mediterranean Diet for six days experienced increased bio-ADM activation and PAM levels mirroring improvement of endothelial function and microcirculation.
“PAM improves age- and Alzheimer’s disease-related cerebral malfunctions,” said Bergmann. “It improves cognition and reduces amyloid load and neuroinflammation, both factors in neurodegeneration. The Cilento lifestyle and diet help too.”
In a small pilot study, Robert Hetzel, MD, a family physician in Gisborne, Victoria, Australia, recruited 23 patients (six females, 17 males) between the ages of 55-79 to follow a “health checklist” for three years. There were five parts:
• Consume a Mediterranean diet, with two low-calorie, alcohol-free days each week
• Exercise 60 minutes daily (aerobics, muscle-building and balance)
• Sleep 7-8 hours each night
• Engage the brain through puzzles, creative arts, music
• Develop social connections
When the study concluded earlier this year, Hetzel reported that 10 patients had significantly changed health behaviors, eight had significantly increased their exercise time and five had fully adopted a Mediterranean diet. Anecdotally, many of the patients reported weight loss, better health and an improved outlook on life.
Hetzel cautioned that the pilot study’s findings were not conclusive, but were encouraging.
“A sample size of 20 patients is too small and a follow-up after just two years too short, but the study results suggest creating a health list for patients to follow can be effective,” said Hetzel, who has proposed a larger study with annual follow-ups over five years and more specific testing for elements like blood lipid levels and metabolites and more specific questions about health behaviors.
“We are generating an unprecedented amount of data,” said Brenner. “The next steps are to develop a platform to integrate these enormous data sets, and interrogate the data with AI to gain new insights into the drivers of healthy aging.”
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.
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.
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 physician-scientist 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.
Cardiologist, University of Catania
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.
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.
Neurologist, Vallo della Lucania Hospital, Salerno
Giovanni Rizzo, MD
Physician, laboratory medicine
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.
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 Living Museum of the Mediterranean Diet in Pioppi – Cilento region–Salerno. Scarano is also a co-principal investigator of the CIAO study.
Assistant professor, Sanford Burnham Prebys
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.
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.
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
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, MD (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, MD, PhD (Italy)
New and ongoing research protocols and descriptions
11:50am–12:15pm
Silvia Ruggeri, BME (Italy) CIAO study update
12:15–12:40pm
Giovanni D’Arena, MD (Italy)
Routine lab testing and analyses in centenarians
12:40–1:05pm
Giovanni Rizzo, MD (Italy)
Laboratory data collection, processing and routine results
1:05–2:05pm Lunch
2:05–2:30pm
Vincenzo Pizza, MD, PhD (Italy)
Neurological behavior in Cilento centenarians
2:30–2:55pm
Barbara Maiese, PhD (Italy)
Psychological assessment in Cilento centenarians
2:55–3:20pm
Giuseppe Scarano, MD (Italy)
Nutritional value of the Mediterranean diet
3:20–3:50pm
Giuseppe Leonardi, MD (Italy)
Genetics in non-ischemic cardiomyopathies—a new point of view
Friday, May 23
Morning session
10-10:30am
Sheldon Morris, MD, MPH (USA)
A study designed to evaluate centenarians’ health
10:30-11am
Allen Wang, PhD (USA)
Mapping human health through cohort-scale, singlecell epigenomics
11-11:30am
Mohit Jain, MD, PhD (USA)
Metabolomic markers of aging and longevity in the Cilento population
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, PhD (USA)
Ameliorating aging through epigenetic interventions
4:20–4:50pm
Alexander Khalessi, MD (USA)
The operating theater as living laboratory: neurological lessons on the science of aging
4:50–5:20pm
Su-Chun Zhang, MD, PhD (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
11:30am-12pm
David Brenner, MD (USA)
Proteomics results from the CIAO study
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
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.
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
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.
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.
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.
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
of clinical cardiovascular disease. And even among those with structural heart abnormalities, symptoms were low.16
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 prevalence
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.
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 onethird 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 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
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.
“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.
Sanford Burnham Prebys sbpdiscovery.org
Scott LaFee VP, Communications slafee@sbpdiscovery.org
Monika Wert-Parkinson Senior Officer, Stewardship and Donor Relations mwert@sbpdiscovery.org
Great Health Science greathealthscience.com
Valeria Albini External Communications valeria.albini@greatnetwork.org
Sanford Stem Cell Institute (UC San Diego) stemcells.ucsd.edu
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THE CIAO STUDY