Projects in Chile

Students at Chile site INVESTIGATORS:

Maria Paulina Correa Burrows, PhD

Raquel Burrows, MD

Rodrigo Troncoso, PhD

Institute of Nutrition & Food Technology (INTA)

University of Chile

Additional support:

Andrea Nicolau del Roure, Assistant, Project Coordinator

Candidates at the Masters and PhD levels are welcome to get involved with one of the following research projects.

Project 1: Obesity as a model of accelerated aging: The ObAGE Study

Purpose:

The overall research goal of ObAGE is to understand how exposure to obesity in critical developmental stages accelerates aging and undermines long-term health in a Chilean historical birth cohort of high social vulnerability. Students 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.

Rationale:

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.

Study design and methods:

The setting for the study 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. Preliminary results of the 30y assessment wave (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..

Anticipated Activities:

Literature review
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.

Techniques/methods students 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 readings:

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 (paulina.correa@inta.uchile.cl).

Project 2: Obesity as a model of accelerated aging- The ObAGE-HLLC Study

Purpose:

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. Participants may choose to work on the following:

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.

Rationale:

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.

Study Design and Methods:

The setting for the study 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. Preliminary results of the 30y assessment wave (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.

Anticipated Activities:

To be further defined when the actual research question is agreed upon:

Literature review
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

Techniques/methods students 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.

Projects in Chile

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