Cilento’s claim to fame in biogerontology stems from its extraordinary concentration of centenarians—individuals aged 100 years and beyond—who paradoxically maintain robust health well past the global average life expectancy of approximately 73.5 years. This phenomenon has attracted intense scientific scrutiny as researchers strive to empirically dissect the intricate interplay of biological, psychological, and social determinants that contribute to delayed aging and extreme longevity. The ongoing CIAO Study, launched in 2015, serves as a multidisciplinary platform employing cutting-edge methodologies including genetics, epigenetics, multi-omics, and advanced clinical phenotyping to decode these longevity determinants systematically.

Central to the CIAO Study’s uniqueness is its focus on the natural population of Acciaroli and surrounding communities within Cilento, an area historically celebrated for its Mediterranean lifestyle—a blend of diet, physical activity, social cohesion, and other behavioral factors believed to collectively foster exceptional healthspan. However, as the investigators underscored, the surface behavioral attributes belie a deeper, cellular architecture of aging that remains to be fully elucidated. Their integrative approach is designed to unravel these molecular hallmarks and identify actionable biological pathways amenable to therapeutic targeting for the broader population.

Prominent highlights from the symposium illustrated the multifactorial nature of aging, structured within the framework of the established “hallmarks of aging,” which categorize cellular and molecular damage into primary, antagonistic, and integrative processes. Paola Antonini, MD, PhD, illuminated the pivotal role of sirtuin-6 (SIRT6), a NAD⁺-dependent deacetylase with diverse epigenetic regulatory functions. SIRT6’s enhancement of DNA repair mechanisms across long-lived species points to a conserved evolutionary strategy mitigating genomic instability, a primary hallmark driving age-associated functional decline and inflammaging—a chronic low-grade inflammatory state implicated in numerous age-related diseases.

Complementing these molecular insights, Sheldon Morris, MD, MPH, provided a clinical portrait contrasting centenarians with younger control cohorts. Intriguingly, centenarians exhibited physiologic parameters typically deemed beneficial for healthy aging: lower blood pressure, body mass index, smoking prevalence, alcohol consumption, and more favorable lipid profiles. Furthermore, sleep duration emerged as a critical behavioral correlate, with most centenarians achieving five or more hours of nightly rest. These clinical phenotypes are not mere anecdotes but are anchored in rigorously gathered data, underscoring evidence-based longevity hallmarks.

At the metabolomic frontier, Mohit Jain, MD, PhD, unveiled compelling discoveries about the metabolic shifts inherent in aging. Their extensive profiling of approximately 30,000 blood metabolites revealed distinct metabolic signatures in centenarians, with significant alterations in hundreds of metabolites that collectively constitute a “metabolic clock.” This biomolecular chronometer transcends chronological age by revealing the biological age of individuals through metabolic health, positioning centenarians as metabolically younger than their years suggest and casting new light on metabolic homeostasis as a key longevity driver.

In a sophisticated systems biology analysis, Sanju Sinha, PhD, presented data on plasma proteomics, highlighting a subset of 57 fibrosis-pathway enriched genes that diverged in centenarians relative to controls. Foremost among these was SERPINE1, a gene encoding Plasminogen Activator Inhibitor-1 (PAI-1), a critical modulator of coagulation and cellular senescence. Emerging evidence intimates that modulating SERPINE1 activity could prolong lifespan and attenuate fibrotic pathologies, making it a tantalizing therapeutic target currently undergoing clinical trials, particularly in oncology and metabolic disorders.

Adding a novel dimension to peptide hormone biology, Andreas Bergmann, PhD, discussed peptidylglycine alpha-amidating monooxygenase (PAM), an enzyme essential for activating over 60 peptide hormones and neuropeptides through C-terminal amidation. This enzymatic step is crucial for regulating vascular, neuronal, metabolic, and cognitive functions. Notably, elevated PAM activity correlates with improved blood-brain barrier integrity, cerebral perfusion, amyloid clearance, and cognitive outcomes in preclinical models. Cilento residents notably exhibit enhanced PAM levels and peptide amidation patterns, which may constitute a biochemical basis for their superior neurological health and longevity.

From a genomic standpoint, Ludmil Alexandrov, PhD, revealed that centenarians in Cilento accumulate fewer single nucleotide variants and insertion-deletion mutations, implicating enhanced genomic stability. Lower telomere attrition rates suggest decelerated cellular aging and hematopoietic maintenance, reinforcing the notion that genome integrity preservation correlates strongly with extended healthspan and lifespan. Telomere dynamics thus serve as critical biomarkers reflective of systemic biological aging processes.

Expanding on the cellular milieu, Peter D. Adams, PhD, shed light on senescence—the permanent cessation of cell division accompanied by a pro-inflammatory secretory phenotype. While cellular senescence confers tumor suppression, its accumulation underlies age-associated tissue dysfunction and chronic inflammation. Experimental interventions targeting MDM2, a molecular regulator of cell cycle and DNA repair, rejuvenated aged murine livers, suppressed frailty, and extended lifespan, signaling promising avenues for translating these molecular discoveries into clinical anti-aging strategies.

Collectively, the CIAO Study epitomizes a paradigm shift in aging research by integrating comprehensive phenotypic characterization with molecular dissection. Its emphasis on a well-defined geographic and genetic cohort enhances the validity and reproducibility of findings, moving beyond anecdotal narratives towards actionable scientific knowledge. The synergistic convergence of omics technologies and clinical insights positions CIAO at the forefront of geroscience, with promising ramifications for public health interventions aimed at extending not just lifespan but healthspan.

Looking ahead, the CIAO initiative envisions expanding its longitudinal scope and interventional studies, propelled by early promising results. The translational potential inherent in modulating identified hallmarks—ranging from epigenetic modifiers and metabolic networks to proteostasis regulators and senolytics—holds considerable promise for redefining the aging experience. With rigorous, standardized methodologies underpinning their approach, CIAO’s roadmap offers a robust template for unraveling the labyrinthine biology of longevity and catalyzing the development of precision interventions to promote healthy aging globally.

Subject of Research: Biological, psychological, and social determinants of healthy aging and extreme longevity in Cilento centenarians.

News Publication Date: 2026-05-22

Web References:

• Sanford Burnham Prebys Medical Discovery Institute, sbpdiscovery.org
• Sanford Stem Cell Institute, stemcells.ucsd.edu
• Great Health Science, greathealthscience.com

Image Credits: Sanford Burnham Prebys

Keywords: Human longevity, healthy aging, centenarians, Cilento region, epigenetics, metabolomics, proteomics, SIRT6, DNA methylation, metabolic clock, peptide hormone amidation, PAM enzyme, telomere attrition, cellular senescence, aging biomarkers

PLOS Aging and Health emerges as a dynamic platform eager to publish boundary-breaking research spanning multiple disciplines that explore the complex processes of aging. The journal’s comprehensive scope is deliberately broad: it integrates biological, developmental, clinical, neurological, and functional perspectives to foster a holistic understanding of aging. Emphasizing multidisciplinary collaboration, it aims to delve into diverse factors influencing aging such as disease progression, cognitive decline, mental health alterations, geriatric care innovations, lifestyle interventions, technological advancements, healthcare delivery systems, social determinants, and policy frameworks. This ambitious scope targets not only the biological mechanisms but also the societal and systemic transformations necessary to promote healthy aging and enhance quality of life at both individual and population levels across diverse demographic groups.

Leading the editorial team of PLOS Aging and Health, Jennifer A. Schrack highlights the journal’s commitment to transcending traditional disciplinary boundaries, which often silo aging research into narrowly defined fields like biology, clinical practice, or policy analysis. Schrack emphasizes that the journal seeks to unify global researchers from diverse backgrounds, clinicians, social scientists, and policymakers to cultivate innovative insights and accelerate scientific breakthroughs. This multidisciplinary ethos is expected to increase the visibility and applicability of research findings by promoting integrative methodologies and cross-sector collaboration, which could ultimately accelerate translational outcomes that benefit broader populations.

Sara Hägg, co-editor-in-chief of PLOS Aging and Health, elaborates on the human-centered approach the journal will embody. She underscores the importance of elucidating both biological mechanisms and clinical relevance, fostering research that bridges fundamental biological insights with practical healthcare applications. Hägg points out that aging research remains an evolving domain attracting increasing scholarly interest, making the journal a timely and critical venue for disseminating studies grounded in open science principles. By embedding rigorous ethical standards and transparency throughout the publication process, the journal aspires to drive reproducibility and foster trust in findings critical to advancing gerontological science.

In parallel, PLOS Ecosystems addresses the very urgent and multifaceted challenges confronting global ecosystems. This journal focuses on the conservation, management, restoration, and sustainable use of terrestrial, freshwater, and marine environments. Distinctively multidisciplinary and community-driven, it invites contributions from both natural and social sciences and encourages interdisciplinary and transdisciplinary research collaborations involving policymakers, resource managers, and practitioners. The journal’s expansive scope covers ecological sustainability across various spatial and temporal scales, examining the complex interdependencies between biodiversity, ecosystem function, and human well-being, thereby positioning itself at the interface of science and society.

Henrique Miguel Pereira, Editor-in-Chief of PLOS Ecosystems, articulates the critical timeliness of launching this journal amid pervasive ecosystem transformations and alarming biodiversity losses worldwide. Pereira accentuates that preserving ecosystems is essential not only for maintaining millions of years of evolutionary heritage but also for addressing interconnected global challenges such as climate change, sustainable agriculture, forestry, fisheries, and urban resilience. By bridging fundamental ecological research with practical environmental management and policy, PLOS Ecosystems aims to foster innovative, science-grounded solutions pivotal for maintaining planetary health and human prosperity.

These journals’ emphasis on open science is central to PLOS’s overarching mission. Open access publishing ensures that vital scientific findings are freely accessible to researchers, practitioners, and the wider public globally, accelerating knowledge exchange and reducing inequality in access to scientific information. By leveraging the Flat Fee publishing model, PLOS innovatively supports institutional subscription schemes that promote broad and equitable participation in the scientific discourse, removing individual monetary barriers that traditionally limit publication opportunities for many researchers.

Lauren Coligan, Publisher at PLOS, underscores the transformative potential of these journals to influence scholarly communication practices within their respective research communities. By extending their portfolio with PLOS Aging and Health and PLOS Ecosystems, PLOS is strategically positioning itself to shape open science norms in fields that are both societally vital and rapidly developing. Rapid access to high-quality, interdisciplinary research published under transparent, ethical frameworks can directly inform policy-making, clinical interventions, ecological restoration efforts, and public health strategies.

The introduction of PLOS Aging and Health and PLOS Ecosystems represents a forward leap in aligning scientific inquiry with urgent real-world challenges. Both journals underscore the necessity of transcending traditional disciplinary silos to foster collaborative, integrative knowledge production. They emphasize the importance of embedding research within open access and open data frameworks to ensure that findings can be systematically validated, reproduced, and extended by others. This approach not only bolsters scientific credibility but also maximizes societal benefit by ensuring wider and faster dissemination of transformative discoveries.

The commitment to addressing aging from a diverse, multidimensional perspective within PLOS Aging and Health reflects growing recognition that aging is not merely a biological inevitability but a complex interplay of physiological, cognitive, social, and environmental factors. Recognizing the policy implications and healthcare system adaptations needed to support healthy aging, this journal promises to provide scientific evidence essential for shaping innovations in prevention, care delivery, and social support systems responsive to shifting demographic realities worldwide.

Similarly, PLOS Ecosystems positions itself as an essential nexus for fostering dialogue among ecologists, social scientists, policymakers, and practitioners navigating the unprecedented environmental crises of our age. By integrating knowledge across disciplines and stakeholder groups, the journal promotes research that not only understands ecosystems in depth but also translates scientific insights into actionable strategies to conserve biodiversity, restore habitat functionality, and mitigate anthropogenic pressures.

Together, these new PLOS journals stand as paragons of the evolving landscape of scholarly publishing, where open access, rigorous peer review, and cross-disciplinary collaboration converge to catalyze innovation and societal impact. They represent a visionary step towards ensuring that scientific progress in aging research and ecosystem science is accessible, actionable, and aligned with the pressing needs of a rapidly changing world.

Subject of Research: Not applicable

Web References:

• PLOS Aging and Health
• PLOS Ecosystems
• PLOS Flat Fee Model
• Public Library of Science (PLOS)

Keywords: Scientific publishing, Medical journals, Scientific journals, Science communication, Academic journals, Open access, Publishing industry, Digital publishing