Centenarian Studies

Amsterdam 100 Plus Study: Research Group of Genomics of Neurodegenerative Disease and Aging

An estimated 60-80% of the chance to develop Alzheimer’s disease depends on genetic factors, and similar percentages apply to other neurodegenerative diseases. Thousands of genetic risk factors are involved: some occur only very rarely in the population, others are more common. Each individual is uniquely vulnerable for developing diseases, which depends on the unique constellation of disease associated genetic variants they inherited from their parents.

Therefore, it is important to know which genetic factors are involved: (1) they point towards the molecular processes underlying the disease, necessary to design accurate treatment strategies. (2) they can be used to predict the individual vulnerability for diseases, far before the onset of symptoms. In the future, when treatment options become available, predicting who is at risk before the onset of symptoms will allow timely and accurate treatment.

Unfortunately, only a fraction of disease associated genetic elements is currently known. To identify novel genetic elements, our group compares the genetic constellations of those affected by neurodegenerative diseases with cognitively healthy individuals. Next to identifying risk-increasing genetic variants, our group takes a unique approach: we aim to identify genetic elements that protect against neurodegenerative diseases.

We conceived the 100-plus Study: an on-going prospective cohort study of centenarians who self-reported to be cognitively healthy, their first-degree family members and their respective partners. By investigating the genetic constellations and biomaterials of those who escaped disease until extreme ages, we aim to learn how cognitive decline can be avoided.

This year our research group is very honored to host the International Centenarian Consortium 2024 in the Netherlands. You can register here:  ICC – Alzheimercentrum Amsterdam

PI: Henne Holstege
Core Team Members: Sven van der Lee, Marc Hulsman, Jana Krizova, Maruelle Luimes
Website: https://holstegelab.eu/

Georgia Centenarian Study

The Georgia Centenarian Study aims to assess adaptation and functioning of very old individuals. The study also hopes to understand what extends genetics and family longevity, experiences in the past, environmental support, individual characteristics, behavioral skills and health behaviors influence longevity, and well-being for very old individuals.

Phase I of the study involved a cross-sectional study examining the unique adaptations of community-dwelling and cognitively-intact centenarians, octogenarians, and sexagenarians in Georgia. This phase was a collaboration among The University of Georgia, Medical College of Georgia, and Iowa State University. Funded by NIMH.

Phase II of the study involved a study of longitudinal changes in adaptation capacity among the three cohorts. Funded by NIMH.

Phase III identified and isolated longevity genes, neuropathology, and functional capacity of a population-based sample of centenarians and controls in 44 counties in Northern Georgia. This phase was a collaboration among The University of Georgia, Tulane University, Boston University, University of Kentucky, Emory University, Duke University, Wayne State University, Iowa State University and University of Michigan. Funded by NIA.

PI: Leonard W. Poon
Core Team Members: Jonathan Arnold, Adam Davey, Michal Jazwinski, Mary Ann Johnson, Peter Martin

Cho, J., Martin, P., & Poon, L. W. (2015). Successful aging and subjective well-being among oldest-old adults: Findings from the Georgia Centenarian Study. The Gerontologist, 55, 132-143.

Rahman-Filipiak, A., Woodard, J. L., Miller, L, Martin, P., Davey, A., & Poon, L. (2014). Octogenarian and centenarian performance on the Fuld Object Memory Evaluation. Aging, Neuropsychology and Cognition. doi: 0.1080/13825585.2014.968085

Da Rosa, G., Martin, P., Gondo, Y., Hirose, N., Ishioka, Y., & Poon, L. W. (2014). Examination of important life experiences of the oldest-old: Cross-cultural comparisons of U. S. and Japanese centenarians. Journal of Cross-Cultural Gerontology, 29, 109-130. doi: 10.1007/s10823-014-9223-z

Cho, J., Martin, P., & Poon, L. W. (2013).  Age group differences in positive and negative affect among oldest-old adults: Findings from the Georgia Centenarian Study. International Journal of Aging and Human Development, 77, 261-288. doi: 10.2190/AG.77.4.a

Martin, P., Jazwinski, M., Davey, A., Green, R., MacDonald, M., Margrett, J., Siegler, I. C., Arnold, J., Woodard, J., Johnson, M. A., Kim, S., Dai, J., Li, L., Batzer, M. A., & Poon, L. W. (2013). APOE ε4, life experiences, and affect among centenarians. Aging and Mental Health. doi: 10.1080/13607863.2013.827624

Iowa Centenarian Study

The Iowa Centenarian Study is a baseline assessment of Iowa centenarians. The objective is to strengthen research of exceptional longevity, particularly in rural areas. The study assesses short-term changes in cognition and activity. During our visits, participants work on a cognition task, a self-rated health test, a life event schedule, a mental health test, and functional abilities test.

PI: Peter Martin
Core Team Members: Jennifer Margrett, Steven Garasky, Warren Franke
Website: https://research.hs.iastate.edu/exceptional-longevity-lab/research/

Margrett, J. A., Hsieh, W-H., Heinz, M., & Martin, P. (2012). Cognitive status and change among Iowa Centenarians. International Journal of Aging and Human Development, 75, 317 – 335. doi: 10.2190/AG.75.4.b

Martin, P., Deshpande, N., Margrett, J., Franke, W., & Garasky, S. (2012). Introduction to the exceptional longevity study of centenarians in rural environments. International Journal of Aging & Human Development, 75(4) 297-316. doi: http://dx.doi.org/10.2190/AG.75.4.a

Franke, W. D., Margrett, J. A., Heinz, M. S., & Martin, P. (2012). Physical and mental health correlates of functional limitations among centenarians. International Journal of Aging & Human Development, 75, 351-363. doi: http://dx.doi.org/10.2190/AG.75.4.d

Garasky, S., Martin, P., Margrett, J. A., & Cho, J. (2012). Perceptions of economic status among centenarians: Associations with activities of daily living, Cognition, depression and institutionalization. International Journal of Aging & Human Development, 75(4) 365-382. doi: http://dx.doi.org/10.2190/AG.75.4.e

Martin, P., da Rosa, G., Margrett, J. A., Garasky, S., & Franke, W. (2012). Stability and change in affect among centenarians. International Journal of Aging & Human Development, 75, 337-349. doi: http://dx.doi.org/10.2190/AG.75.4.c

PT100 | The Oporto Centenarian Study

As the first Portuguese population-based study on centenarians, the PT100 Oporto Centenarian Study aimed to describe the characteristics of those individuals who have reached 100 years old and enrich the available knowledge on the exceptional longevity phenomenon in Portugal. By comprehensively portraying their living situation, care needs, physical health, psychological strengths and cognitive functioning, the study and its several satellite projects aim to increase the available information on the challenges of living beyond 100 years. 

PI: Oscar Ribeiro
Core team members: Lia Araújo, Laetitia Teixeira, Rosa Marina Afonso, Constança Paúl
Website: www.pt100.pt

Sydney Centenarian Study: ICC-Dementia

ICC-Dementia is a dementia work group of the International Consortium of Centenarian (ICC) studies brought together to examine the prevalence of and risk factors for dementia that are robust across centenarian cohorts from around the world. ICC-Dementia was formed in 2012 and comprises eighteen centenarian and near-centenarian studies from Asia, Europe, the Americas, and Oceania. ICC-Dementia seeks to harmonise data from these studies to describe the cognitive and functional profiles of the exceptionally old individuals. The bringing together of such diverse ethnoracial and sociocultural studies allows us to explore systematically the factors for dementia and longevity, as well as provides real-life models of healthy brain ageing.

Key Personnel

Group Leaders:

  • Scientia Professor Perminder Sachdev
  • Scientia Professor Henry Brodaty

CHeBA Team:

  • Dr John Crawford, Senior Research Officer
  • Dr Nicole Kochan, Senior Research Fellow
  • Dr Karen Mather, Senior Research Fellow
  • Dr Yvonne Leung, Research Fellow (Adjunct)
  • Ms Fleur Harrison, PhD Student

Webpage: ICC-Dementia | Centre for Healthy Brain Ageing (CHeBA) (unsw.edu.au)

New England Centenarian Study

The New England Centenarian study (NECS) began in 1995 and is based at Boston University School of Medicine. As one of the first studies to describe families that demonstrate clustering for exceptional longevity, the NECS is a founding partner of the National Institute on Aging-funded Long Life Family Study (LLFS), now in its 20th year. The LLFS is a multi-center effort to enroll families clustered for exceptional survival in order to identify environmental and genetic factors that promote long healthy lives in these family members.

The NECS and especially the biostatics and genomics efforts led by Paola Sebastiani PhD pioneered the discovery that specific combinations of protective genes play an important role in the ability to live to 100 and an even more important role to live to more rare ages such as 105 (“semi-supercentenarian”) or 110 (“supercentenarian”). These gene combinations that can be different for different families, ancestry backgrounds etc., likely slow aging and decrease risk for aging related diseases. Two other NIA-funded studies run by the NECS, the Integrative Longevity Omics Study (ILO) and the Longevity Consortium’s Centenarian Project (LCCP) recruit and enroll centenarians, their siblings, offspring and offspring spouses to collect detailed family pedigree, medical history, carefully collected cognitive function data and blood and stool samples. The blood samples are used to generate a huge amount of data about the proteins, metabolites, and genes that we then study for their association with exceptional longevity and traits like delaying or escaping Alzheimer’s disease. With the stool sample, we are able to determine what types of bacteria live in the study participant’s gut (this is called the microbiome) and the healthy (or unhealthy) substances those bacteria produce and cross into the blood stream. These substances play roles in health and disease and likely aging. We hope to use these data to discover biomarkers of healthy aging and longevity and to also decipher the biological mechanisms of resilience and resistance to aging related diseases and stressors that accelerate aging.

Another very interesting approach we are taking is to collect blood samples from specific participants and provide those to Dr. George Murphy at Boston University’s Center for Regenerative Medicine where the samples are used to generate induced pluripotent stem cell (iPSC) lines which are both stored and also differentiated into specific cell types, for example, cortical neurons. These neurons, in culture, are then subjected to stressors that mimic accelerated aging and in vitro transcriptomic, metabolomic and other omics data are generated again, to understand underlying biological mechanisms of resilience and resistance.

Under the leadership of Stacy Andersen PhD, co-Director of the NECS and director of our cognitive and physical function studies, the NECS has also shown that centenarians, despite having an abundance of the most important risk factor for dementia, age, they paradoxically delay or escape Alzheimer’s disease and other dementias. Very much in agreement with Amsterdam 100 Plus Study findings, centenarians are resilient and, in some cases, even resistant to these diseases. Dr. Andersen’s work paved the way for our fourth NIA-funded study, Resilience and Resistance to Alzheimer’s Disease in Centenarians and Offspring (RADCO). In that study we measure biomarkers for AD and neurodegeneration from participants’ blood samples, perform a brain MRI and perform comprehensive neuropathological studies of post-mortem brain donations and assess those results in the context of comprehensive neurocognitive assessments that are performed annually with the centenarians and every two years with the offspring. Our goal is to discover predictors or markers and underlying biological mechanisms of exceptional cognitive function at these very old ages (called cognitive superaging) and of resilience or resistance against AD and other dementias.

Data Sharing: All phenotypic and omics data that we generate is/will be available for sharing via the NIA-funded Exceptional Longevity Translational Resources (ELITE) web portal.

Director: Thomas Perls MD, Co-Director: Stacy Andersen PhD
Core Team Members (at Boston University unless otherwise noted): Paola Sebastiani PhD (Tufts Medical Center), Stefano Monti PhD, George Murphy PhD, Sofiya Milman MD (Einstein College of Medicine), Daniel Segre PhD, Albert Tai PhD (Tufts University), Susan Bookheimer PhD (UCLA), Vonetta Dotson PhD (Vera Gorbunova PhD (University of Rochester), Adam Brickman PhD (Columbia University), Doo Yeon Kim (Harvard Medical School), Winston Hide PhD (Harvard Medical School), David Salat PhD (Harvard Medical School), Bradley Dickerson PhD (Harvard Medical School), Rudy Tanzi PhD (Harvard Medical School), Shino Magaki PhD (UCLA)
Website: https://www.bumc.bu.edu/centenarian/

Oklahoma 100 Year Life Project (Oklahoma Centenarian Study)

The purpose of the Oklahoma 100 Year Life Project (Oklahoma Centenarian Study) is to provide a publicly shared collection of video/audio documented and qualitatively transcribed oral storytelling histories of centenarians residing in the state of Oklahoma. Of particular interest is to use this collection to advance applied understanding of social and cultural influences and narrative identity processes essential to centenarian life course development. In addition, this study employs the use of qualitative and mixed-methodologies, as well as AI-base predictive modeling methods to identify autobiographical, narrative-based, and historical markers of development essential to survivorship and continued longevity beyond 100 years of age.

Key Personnel

PI/Co-PI:  Alex J. Bishop & Tonya Finchum

Collaborators:  Julie Pearson-Little Thunder, Maria Beach, Melinda Heinz, Patrick Deglaris, Mohammad Fili

Beach, M., Bishop, A.J., Finchum, T., & Thunder, J.P.L. (2021). Oral history performance as interdisciplinary collaboration. Journal of Dramatic Theory and Criticism 36(1), 171-181. https://doi.org/10.1353/dtc.2021.0030.

Bishop, A. J., Pearson Little-Thunder, J. Finchum, T., & Beach, M. (2019). The Oklahoma 100 Year Life Project as an instructional tool to transform student engagement and pedagogy in gerontological education. The International Journal of Reminiscence and Life Review, 6 (1) 4-9. https://journals.radford.edu/index.php/IJRLR

Jones N. F., Bishop, A. J., & Finchum, T. (2022). Considering the relevance of childhood religious experiences through centenarian oral histories. International Journal of Aging and Human Development, 94(1),93-111. doi: 10.1177/00914150211050883

Heinz M, Bishop AJ, Finchum T. (2021). The lived experiences of African American centenarians: Narrative exploration from a life course theory perspective. Gerontologist, 61(8), 1266-1276. doi: 10.1093/geront/gnab052