Projects in Chile
Investigators:
University of Chile
Additional support: Andrea Nicolau del Roure, Assistant, Project Coordinator, INTA
University of Michgian Mentors:
Anna Baylin, MD, DrPH, Associate Professor, Nutritional Sciences
Karen Peterson, DSc, Stanley M. Garn Collegiate Professor of Nutritional Sciences
Candidates at the Masters and PhD levels are welcome to apply for a placement at this site. Trainees must be fluent in Spanish to qualify.
Instituto de Nutricion y Tecnologia de los Alimentos (INTA) de la Universidad de Chile, Santiago, Chile
The Center for Research in Food Environments and Nutrition-Related Chronic Diseases (CIAPEC) at INTA, University of Chile is looking to contribute to the prevention of obesity and non-communicable diseases with a focus on equity and life course. During the last 10-15 years, we have been working on characterizing different aspects of the food environment (i.e. food composition and labeling, food marketing, food availability, among others), along with longitudinal assessments of feeding practices, diet and weight status among populations in different stages of the life cycle (i.e. infancy, adiposity rebound, adolescence, pregnancy and adulthood).
The setting for the studies at this site is Chile's oldest birth epidemiological birth cohort: the Santiago Longitudinal Study. The SLS consists of ≈1000 Chileans at 30-31y, 50% females, of low- to middle SES, who participated in research related to nutrition and development since birth with follow-up at 1y, 5y, 10y, 12y, 14y, 16y, 21y, 23y and 29y. They were born in 1992-1996, at term, of uncomplicated vaginal births, weighed >3 kg, and were free of acute or chronic health problems. Enrollment occurred just as the country entered a period of rapid socioeconomic and epidemiological changes. When participants were 16y, they got involved in a study of ‘Biopsychosocial determinants of adolescent obesity’. Assessment of anthropometric and cardiometabolic markers was repeated at 23y, and a third wave is ongoing.
Placement 1: Projects with Maria Paulina Burrows, PhD
Project 1: Obesity as a model of accelerated aging- The ObAGE Study
The ObAGE Study (DOI: 10.1186/s12877-022-03032-4) brings together geroscience, public health, epidemiology, clinical medicine (geriatrics and endocrinology), and social sciences, aiming to create a transdisciplinary node connecting research, knowledge, and expertise to explore how exposure to obesity in key developmental stages disrupts homeostatic resilience mechanisms that preserve physiological integrity and prevent the early expression of aging phenotypes. We expect to better understand how obesity accelerates the rate of aging at multiple levels (from cells to organ systems) and determine whether social position influences vulnerability to obesity as a risk factor for accelerated aging. Our work also seeks to stimulate public debate and awareness on these topics as well as inform public policymaking with evidence-based research.
Preliminary results of the 30y assessment wave of the SLS (n=289) show that mean BMI is 30 Kg/m2 with a dramatic increase in obesity (48%), MetS (42%), IR (59%), NAFLD (62%) and inflammation (37%). Significant alterations in participants’ glucose/lipid profiles, pulse wave velocity and carotid intima-media thickness at 30y are consistent with high cardiometabolic risk. Our data strongly suggest that SLS participants are aging faster than physiologically normal due to early exposure to obesity. This intuition must be confirmed moving down from the organ systems to the cellular and molecular levels to get robust evidence that obesity is an aging driver. The age of SLS participants (<35y) makes them particularly appealing in testing this hypothesis and may boost a paradigm shift in aging research by approaching aging and its consequences from the early stages of a person's life. Students may choose to get involved in fieldwork with SLS participants (e.g., involvement in minor medical procedures or passing health-related questionnaires) or do lab work using blood or saliva samples collected during fieldwork. Those choosing to work on research aim three may get involved in the HIIT setting up and development. Fieldwork with participants takes place in the Obesity Clinic at INTA, lab work occurs in the Lab for Nutrition and Physical Activity Research. Both are located at INTA, Universidad de Chile.
Trainees may choose to work on one of the following research aims:
- To investigate whether obesity in key developmental stages triggers an early expression of aging at multiple levels (from cells to systems) in adults <35y;
- To determine whether exposure to early psychosocial adversity (e.g., child abuse and neglect, witnessing family violence, having a parent with untreated mental illness, financial distress, etc.) confers greater vulnerability to obesity-induced accelerated aging;
- To investigate the autophagy response in peripheral blood mononuclear cells (PBMCs) following an acute bout of high-intensity interval training (HIIT) with treadmill running in obese vs. non-obese participants.
The specific research question of the project will be agreed between the fellow and the researchers.
Trainees will play a crucial role in the project by:
- Conducting literature reviews
- Statistical analyses with data already collected
- Interpretation of the results according to the rationale, what is known in the field and public policy implications
- Communication of results (to participants, health authorities, or the scientific community); writing of an abstract to be presented in a scientific meeting or a manuscript.
Methods trainees should be familiar with:
- Data management
- Basic descriptive statics
- Multivariable analyses (preferable)
- Longitudinal analyses (preferable)
- Molecular biology skills in the following areas will be positively considered for those choosing lab work: ELISA, cell/tissue culture, preparing regents, gel electrophoresis, centrifugation, protein immunoblot, high throughput screening.
- While knowledge of machine learning and programming skills are not mandatory, they will be positively considered.
** Given the complexity of the data and analyses, a postgrad is needed for this project. Candidates should be interested in topics that fit into ObAGE’s research agenda, such as biopsychosocial determinants of obesity/cardiometabolic risk, epigenetic age, chronic inflammation, and autophagy response to exercise, among others. They must have been trained in disciplines like social epidemiology, clinical epidemiology, biomedical science, cellular and molecular biology, and biochemistry, among others.
Suggested literature for the project:
Aims 1 and 3:
- Correa-Burrows P, Burrows R, Albala C, Court FA, Salech F, Sanhueza G, Gonzalez-Billault C. Multiple events case-control study in a prospective cohort to identify systemic, cellular, and molecular biomarkers of obesity-induced accelerated aging in 30-years-olds: the ObAGE study protocol. BMC Geriatr. 2022 May 2;22(1):387. doi: 10.1186/s12877-022-03032-4.
- Salvestrini V, Sell C, Lorenzini A. Obesity May Accelerate the Aging Process. Front Endocrinol. 2019;10:266. doi: 10.3389/fendo.2019.00266.
- Tam B, Morais J, Santosa S. Obesity and ageing: Two sides of the same coin. Obe Rev. 2020;21:e12991. doi: 10.1111/obr.12991.
- Horvath S, Erhart W, Brosch M, et al. Obesity accelerates epigenetic aging of human liver. Proc Natl Acad Sci. 2014;111:15538–15543. doi: 10.1073/pnas.1412759111.
- Oblak L, van der Zaag J, Higgins-Chen AT, Levine ME, Boks MP. A systematic review
of biological, social and environmental factors associated with epigenetic clock acceleration.
Ageing Res Rev. 2021 Aug;69:101348. doi: 10.1016/j.arr.2021.101348.
Aim 2:
- Crimmins E. Social hallmarks of aging: Suggestions for geroscience research. Ageing Res Rev. 2020;63:101136. doi: 10.1016/j.arr.2020.101136.
- Klopack ET, Crimmins EM, Cole SW, Seeman TE, Carroll JE. Accelerated epigenetic aging mediates link between adverse childhood experiences and depressive symptoms in older adults: Results from the Health and Retirement Study. SSM Popul Health. 2022 Mar 16;17:101071. doi: 10.1016/j.ssmph.2022.101071
- Tang R, Howe LD, Suderman M, Relton CL, Crawford AA, Houtepen LC. Adverse childhood experiences, DNA methylation age acceleration, and cortisol in UK children: a prospective population-based cohort study. Clin Epigenetics. 2020 Apr 7;12(1):55. doi: 10.1186/s13148-020-00844-2.
More reading material can be requested to Dr. Correa ([email protected]).
Project 2: Obesity as a model of accelerated aging- The ObAGE-HLLC Study
The ObAGE Study (DOI: 10.1186/s12877-022-03032-4) brings together geroscience, public health, epidemiology, clinical medicine, and social sciences to explore how exposure to obesity in key developmental stages disrupt homeostatic resilience mechanisms that preserve physiological integrity and prevent the early expression of aging phenotypes. The ObAGE study became a member of the Hispanic Latino Lipid Consortium in April 2023. This consortium is a partnership between longitudinal studies conducted in the US (Cameron County Hispanic Cohort and Hispanic Community Health Study) and Chile (Santiago Longitudinal Study) aiming to investigate whether cardiometabolic risk and aging phenotypes are expressed differently in diverse Hispanic populations, due to molecular differences in specific cells and tissues. Our research aims to gain a deeper understanding of how obesity accelerates the aging process across various levels, ranging from cells to organ systems, particularly in groups that are underrepresented in aging research. Additionally, we hope to raise public awareness and encourage discussions regarding these topics, while advocating for the use of evidence-based research to inform policymaking.
Preliminary results of the 30y assessment wave of the SLS (n=206) show that mean BMI is 30 Kg/m2 with a dramatic increase in obesity (48%), MetS (42%), IR (59%), NAFLD (62%) and inflammation (37%). Significant alterations in participants’ glucose/lipid profiles, pulse wave velocity and carotid intima-media thickness at 30y are consistent with high cardiometabolic risk. DNAm age data shows that individuals with a long history of obesity have an epigenetic age that is 15-20% higher than their chronological age. On the other hand, those who have always maintained a healthy BMI show no difference between their biological and chronological age. These findings suggest that different biological clocks tick at different rates and that long-term obesity can significantly affect the pace of biological aging. The next step is to confirm whether other hallmarks of aging, as proposed by Lopez-Otin et al., are expressed in ObAGE participants exploring key features in specific cells and tissues. The age of SLS participants (<35y) makes them particularly appealing in testing this hypothesis and may boost a paradigm shift in aging research by approaching aging and its consequences from the early stages of a person's life. Students may get involved in fieldwork with SLS participants or do lab work as described above. Fieldwork with participants takes place in the Obesity Clinic at INTA, lab work occurs in the Lab for Nutrition and Physical Activity Research. Both are located at INTA, Universidad de Chile.
The goal of this project is to investigate the role of multi-tissue gene expression (WB and SAT) and changes in WB expression over time to identify key modifiable molecular signatures associated with cardiometabolic diseases in a diverse sample of Hispanic Latinos. Of particular interest is to determine whether age-related alterations in WAT and resident immune cells are observed in younger age individuals (<35y) long exposed to obesity, suggesting an early expression of aging phenotypes.
Trainees may choose to work on the following research aims:
- Field work, including assisting with biopsy procedures to obtain adipose tissue.
- Laboratory work, including isolation of peripheral blood mononuclear cells (PBMCs) and the proper management, aliquoting, and storage of adipose tissue.
- Analysis of epidemiological data, including biopsychosocial determinants of health and disease, along with systemic, cellular, and molecular biomarkers of chronic diseases.
The specific research question of the project will be agreed between the fellow and the researchers.
Trainees will play a crucial role in the project by:
- Conducting literature reviews
- Statistical analyses with data already collected
- Interpretation of the results according to the rationale, what is known in the field and public policy implications
- Communication of results (to participants, health authorities, or the scientific community); writing of an abstract to be presented in a scientific meeting or a manuscript
Methods trainees should be familiar with:
- Data management
- Basic descriptive statics
- Multivariable analyses (preferable)
- Longitudinal analyses (preferable)
- Molecular biology skills in the following areas will be positively considered for those choosing lab work: ELISA, cell/tissue culture, preparing regents, gel electrophoresis, centrifugation, protein immunoblot, and high throughput screening.
- While knowledge of machine learning and programming skills are not mandatory, they will be positively considered.
** Given the complexity of the data and analyses, a postgrad is needed for this project. Candidates should be interested in topics that fit into ObAGE’s research agenda, such as biopsychosocial determinants of obesity/cardiometabolic risk, epigenetic age, chronic inflammation, and autophagy response to exercise, among others. They must have been trained in disciplines like social epidemiology, clinical epidemiology, biomedical science, cellular and molecular biology, and biochemistry, among others.
Suggested literature for the project:
- López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. Hallmarks of aging: An expanding universe. Cell. 2023 Jan 19;186(2):243-278. doi: 10.1016/j.cell.2022.11.001.
- Correa-Burrows P, Burrows R, Albala C, Court FA, Salech F, Sanhueza G, Gonzalez-Billault C. Multiple events case-control study in a prospective cohort to identify systemic, cellular, and molecular biomarkers of obesity-induced accelerated aging in 30-years-olds: the ObAGE study protocol. BMC Geriatr. 2022 May 2;22(1):387. doi: 10.1186/s12877-022-03032-4.
- Salvestrini V, Sell C, Lorenzini A. Obesity May Accelerate the Aging Process. Front Endocrinol. 2019;10:266. doi: 10.3389/fendo.2019.00266.
- Tam B, Morais J, Santosa S. Obesity and ageing: Two sides of the same coin. Obe Rev. 2020;21:e12991. doi: 10.1111/obr.12991.
- Horvath S, Erhart W, Brosch M, et al. Obesity accelerates epigenetic aging of human liver. Proc Natl Acad Sci. 2014;111:15538–15543. doi: 10.1073/pnas.1412759111.
- Oblak L, van der Zaag J, Higgins-Chen AT, Levine ME, Boks MP. A systematic review of biological, social and environmental factors associated with epigenetic clock acceleration. Ageing Res Rev. 2021 Aug;69:101348. doi: 10.1016/j.arr.2021.101348.
- Crimmins E. Social hallmarks of aging: Suggestions for geroscience research. Ageing Res Rev. 2020;63:101136. doi: 10.1016/j.arr.2020.101136.
- Klopack ET, Crimmins EM, Cole SW, Seeman TE, Carroll JE. Accelerated epigenetic aging mediates link between adverse childhood experiences and depressive symptoms in older adults: Results from the Health and Retirement Study. SSM Popul Health. 2022 Mar 16;17:101071. doi: 10.1016/j.ssmph.2022.101071
- Tang R, Howe LD, Suderman M, Relton CL, Crawford AA, Houtepen LC. Adverse childhood experiences, DNA methylation age acceleration, and cortisol in UK children: a prospective population-based cohort study. Clin Epigenetics. 2020 Apr 7;12(1):55. doi: 10.1186/s13148-020-00844-2.
More reading material can be requested to Dr. Correa ([email protected]).
Additional information about this site:
Santiago is the capital and largest city of Chile and one of the largest cities in the Americas. It is located in the country's central valley and is the center of the Santiago Metropolitan Region, which has a population of seven million, representing 40% of Chile's total population. Most of the city is situated between 500–650 m (1,640–2,133 ft)above sea level.
The Institute of Nutrition and Food Technology (INTA) is part of the University of Chile campus. University of Chile is a public research university, and the oldest university in the country.
Andrea Nicolau del Roure, Assistant, Project Coordinator at INTA, has worked with MHRT trainees for many years supporting their onboarding, orientation, and experience in Chile. Trainees will stay at a home stay or at a retal apartment within commuting distance of INTA. Trainees should be fluent in Spanish to navigate the commute, campus and work at INTA.