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Childhood stress may biologically age pregnant moms

Pregnant women growing up in poor circumstances, prematurely age on a cellular level raising risks to their and their baby's health.


Ohio State University researchers examined blood from pregnant women to evaluate the length of their telomeres - dense protein structures at the end of each chromosome that wear away over time. Shorter telomeres indicate an older cellular age and are used in science to measure biologic as opposed to chronologic age.
Researchers found that women who reported low socioeconomic status as kids and who struggled with family support as adults were biologically older, as indicated by their shorter telomeres.

Previous research had already established women with low socioeconomic status and psychosocial risk factors, have worse birth outcomes. Cellular aging found in this current study is possibly one explanation for such results. "Access to support, care and resources is so important to expectant moms," says Lisa Christian, senior author and researcher at Ohio State Wexner Medical Center's Institute for Behavioral Medicine Research.

The 81 pregnant women in the study were 25 years old on average and racially diverse. Each was evaluated during all three trimesters and then about two months following delivery. Trauma and low socioeconomic status during childhood, along with current social support, were captured in questionnaires each woman filled out.
Family social support - but not support from partners or friends - emerged as a strong predictor of telomere length, as did low socioeconomic status during childhood.

Advanced maternal age is defined by doctors as 35 or older and is well-understood to put women at higher risk for babies born with medical and developmental challenges. It is possible advanced cellular age may do the same, according to Amanda Mitchell, lead author, now Assistant Professor in the Department of Counseling and Human Development at the University of Louisville, Kentucky, USA.

Mitchell: "We wonder how biological age factors in? We know younger mothers can have poor birth outcomes, that chronological age is not a perfect predictor of birth outcomes."

Telomeres can also lengthen — reducing biological ageing. Elizabeth Blackburn, Carol W. Greider and Jack W. Szostak who together co-discovered that the enzyme telomerase replenishes telomeres, were awarded the 2009 Nobel Prize in Physiology or Medicine.
For now, telomere assessment is strictly used only in research and not in clinical practice. But in the future, research into cell aging may prompt useful interventions into women's health planning.

Abstract Highlights
• SLC38A9 is a lysosomal arginine sensor for the mTORC1 pathway
• SLC38A9 transports several essential amino acids in an arginine-regulated fashion
• Leucine produced via lysosomal proteolysis requires SLC38A9 to activate mTORC1
• SLC38A9 is required for macropinocytosed protein to support pancreatic tumor growth

Summary
The mTORC1 kinase is a master growth regulator that senses many environmental cues, including amino acids. Activation of mTORC1 by arginine requires SLC38A9, a poorly understood lysosomal membrane protein with homology to amino acid transporters. Here, we validate that SLC38A9 is an arginine sensor for the mTORC1 pathway, and we uncover an unexpectedly central role for SLC38A9 in amino acid homeostasis. SLC38A9 mediates the transport, in an arginine-regulated fashion, of many essential amino acids out of lysosomes, including leucine, which mTORC1 senses through the cytosolic Sestrin proteins. SLC38A9 is necessary for leucine generated via lysosomal proteolysis to exit lysosomes and activate mTORC1. Pancreatic cancer cells, which use macropinocytosed protein as a nutrient source, require SLC38A9 to form tumors. Thus, through SLC38A9, arginine serves as a lysosomal messenger that couples mTORC1 activation to the release from lysosomes of the essential amino acids needed to drive cell growth.

Authors: Gregory A. Wyant, Monther Abu-Remaileh, Rachel L. Wolfson, Walter W. Chen, Elizaveta Freinkman, Laura V. Danai, Matthew G. Vander Heiden, David M. Sabatini

Keywords: amino acid sensing, nutrient sensing, mTOR, lysosome, micropinocytosis, autophagy

The National Institutes of Health and National Center for Advancing Translational Sciences supported the study.

Jennifer Kowalsky of Ohio State's the Institute for Behavioral Medicine Research also worked on the study, as did researchers from the University of California San Francisco.

This work was supported by the National Institutes of Health (NIH, R01 CA103866, R01 CA129105, R37 AI47389, T32 GM007753, F30 CA189333, and F32CA210421), the Department of Defense (W81XWH-15-1-0230, W81XWH-15-1-0337), the European Molecular Biology Organization (EMBO), the Lustgarten Foundation, Stand Up To Cancer (SU2C), the National Cancer Institute (NCI, R01 CA168653, P30CA1405141), and Howard Hughes Medical Institute. David Sabatini's primary affiliation is with Whitehead Institute for Biomedical Research, where his laboratory is located and all his research is conducted. He is also a Howard Hughes Medical Institute investigator and a professor of biology at Massachusetts Institute of Technology.

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Oct 24, 2017   Fetal Timeline   Maternal Timeline   News   News Archive




'Migrant Mother,' by Dorothea Lange and one of her most recognized images. Florence Owens Thompson, her three children and husband, were suffering from lack of work and food as pickers during the 'Great Depression.' Lange's photographs informed federal authorities about the plight of these families, and aid was sent to the camp to prevent starvation. Image Credit: Dorothea Lange, 1936


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