Protective Influences of Postnatal Development on Adult Health Trajectories/Outcomes in Humans

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Audience

Researchers from a variety of scientific fields including pediatrics, developmental biology, epidemiologic studies on children and adults, biomedical aging research, and program staff from NIA, NICHD and other NIH ICs.

Dates

June 20, 2024 | 12:00 p.m. – 5:30p.m. ET

June 21, 2024 | 9:00 a.m. – 3:45 p.m. ET

Purpose and Background

The period spanning childhood and adolescence is unique in the human life history not only for major gains in growth and development that are attained but also for a significant decline in mortality which begins in early postnatal life hitting a nadir at around 10 years of age. After that, the mortality rate starts increasing again and continues in a monotonic fashion for the rest of the life span. This workshop considered approaches to expand the limited current knowledge about differences among human juvenile stages and adulthood in factors affecting disease susceptibility, their mechanistic underpinnings, and their effects on health and disease outcomes of later life stages. Greater knowledge about factors responsible for juvenile phenotypes or maturational changes could have implications for translational research on potential health effects in adult life of modulating such factors during youth or during adulthood.

The goals of this workshop were to:

• Review the current state of knowledge of phenomena in humans and potential underlying mechanisms (whether it is derived from human-based platforms or model organisms),
• Discuss features/resources of extant cohorts that could be leveraged for future studies,
• Identify opportunities for collaborations and resource needs. 

Agenda

All times are in Eastern Daylight Time.

Day 1 | Thursday, June 20

12:00 p.m.: Session 1 | Framework
Moderator: Evan Hadley, M.D.

• Conceptual Framework: Relationships Between Development and Aging, Evan Hadley M.D., NIA
• Demographic and developmental factors in human healthspan evolution, Caleb Finch Ph.D., USC
• Relationship between development, aging and mortality, Vadim Gladyshev, Ph.D., Harvard University
• Germline mutation rates in young adults, predict longevity and reproductive lifespan, and may be established around the time of puberty, Richard Cawthon, M.D. Ph.D., University of Utah
• Protective Factors and DOHaD:  Synergies and Distinctions, Matt Gillman, M.D., S.M., NIH OD
• Discussion

2:30 p.m.: Break

2:45 p.m.: Session 2 | Differences in responses to biological stressors across juvenile developmental stages and adulthood and underlying mechanisms/factors 
Moderator: Chhanda Dutta, Ph.D.

Infections and Bone/Cartilage Injuries

• Peak resilience to infectious disease is observed in school-age children, Judith Glynn, M.Sc., Ph.D., London School of Hygiene & Tropical Medicine
• Age-dependent metabolic mechanisms contribute to susceptibility to sepsis, Basilia Zingarelli, M.D., Ph.D., University of Cincinnati
• Dynamic regulation of apoptotic cell death across tissues and age impact responses to SARS-CoV-2 infection and other sources of damage or stress, Kristopher Sarosiek, Ph.D., Harvard University
• Gene expression changes in immune cells during the peripubertal period, Francesca Luca, Ph.D., Wayne State University
• Circulating osteogenic cells and cellular senescence: contrasting roles in skeletal growth, injury and aging, Sundeep Khosla, M.D., Mayo Clinic
• Characterization of fracture repair in juvenile, middle-aged and old mice with regards to 1) molecular, cellular, and histological progression of skeletal repair and 2) changes in vascularization and inflammatory responses observed with aging, Ralph Marcucio, Ph.D., UCSF
• Harnessing the regenerative potential of juvenile cartilage, Nidhi Bhutani, M.D., Stanford University
• Discussion

5:20 p.m.: Adjourn
 

Day 2 | Friday, June 21

9:00 a.m.: Session 3 | Differences in risk for chronic diseases across juvenile developmental stages and adulthood and underlying mechanisms/factors 
Moderator: Chunyan He, Ph.D., NIA

CVD, Metabolic Syndrome and Cancer

• Early life vascular risk factors and adult cardiovascular outcomes, Lydia Bazzano, M.D., Ph.D., Tulane University
• Differential impact of puberty and sex hormones on serum metabolomic profile of young people with relevance for cardiovascular risk, Coziana Ciurtin, M.D., University College London
• The roles of gonadal hormones and sex chromosome complement in cardiometabolic health, Karen Reue, Ph.D., UCLA
• Genetics of puberty timing and relations to later life health outcomes (CVD, T2DM), Joanne Murabito, M.D., Boston University
• Markers of child growth predict adult risk factors for metabolic diseases, Shumei Sun, Ph.D., Virginia Commonwealth University

10:40 a.m.: Break

• Older age at sexual maturation is causally linked to a reduced risk of later prostate cancer, especially aggressive disease, Sarah Lewis, Ph.D., University of Bristol
• Later ages at menarche are associated with lower risks for seven different cancers, Barbara Fuhrman, Ph.D., USUHS
• Discussion
• Sessions 2 & 3 | Panel Discussion 

12:45 p.m.: Session 4 | Future Research Directions and Resource Needs (Working Lunch)
Moderator: Francesca Macchiarini, Ph.D.

• An overview of the ECHO Cohort and data available to the public, Clay Mash, Ph.D., NIH OD
• Examples of studies leveraging extant longitudinal cohorts and data/biological repositories; analytical approaches, Shumei Sun, Ph.D., Virginia Commonwealth University
• Opportunities for mechanistic studies in clinical translational models using human in vitro platforms, Basilia Zingarelli, M.D., Ph.D., University of Cincinnati
• Opportunities for examining wound healing, Marty Visscher, Ph.D., University of Cincinnati
• Plenary discussion on the use and integration of cohort studies, stored biospecimens from extant cohorts, biological sample collection methods, human in vitro systems, animal models, and analysis platforms.

3:30 p.m.: Concluding Remarks
Chhanda Dutta, Ph.D. and Francesca Macchiarini, Ph.D., NIA

3:45 p.m.: Adjourn

Please contact Francesca Macchiarini at [email protected] for questions you have about the workshop.