Relationships Between Telomere Length, Plasma Glucagon-like Peptide 1, and Insulin in Early-Life Stress-Exposed Nonhuman Primates

Kathryn K Ridout; Shariful A Syed; Hung-Teh Kao; Barbara Porton; Anna V Rozenboym; Jean Tang; Sasha Fulton; Tarique Perera; Andrea P Jackowski; John G Kral; Audrey R Tyrka; Jeremy Coplan

doi:10.1016/j.bpsgos.2021.07.006

Relationships Between Telomere Length, Plasma Glucagon-like Peptide 1, and Insulin in Early-Life Stress-Exposed Nonhuman Primates

Biol Psychiatry Glob Open Sci. 2021 Aug 3;2(1):54-60. doi: 10.1016/j.bpsgos.2021.07.006. eCollection 2022 Jan.

Authors

Kathryn K Ridout^{1

2}, Shariful A Syed³, Hung-Teh Kao⁴, Barbara Porton⁴, Anna V Rozenboym⁵, Jean Tang⁶, Sasha Fulton⁷, Tarique Perera⁸, Andrea P Jackowski⁹, John G Kral¹⁰, Audrey R Tyrka^{4

11}, Jeremy Coplan¹²

Affiliations

¹ Department of Psychiatry, The Permanente Medical Group, Santa Rosa, California.
² Division of Research, Kaiser Permanente Northern California, Oakland, California.
³ Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut.
⁴ Laboratory for Clinical and Translational Neuroscience, Brown University, Providence, Rhode Island.
⁵ Department of Biological Sciences, Kingsborough Community College, City University of New York, Brooklyn, New York.
⁶ Department of Psychiatry, College of Physicians and Surgeons, Columbia University Medical Center and New York State Psychiatric Institute, New York, New York.
⁷ Department of Psychiatry, Mount Sinai Medical Center, New York, New York.
⁸ Contemporary Care, Danbury, Connecticut.
⁹ Departamento de Psiquiatria, Universidade Federal de São Paulo, São Paulo, Brazil.
¹⁰ Department of Internal Medicine & Surgery, SUNY Downstate, Brooklyn, New York.
¹¹ Department of Psychiatry and Human Behavior, Brown University, Providence, Rhode Island.
¹² Department of Psychiatry & Behavioral Sciences, State University of New York Downstate Medical Center, Brooklyn, New York.

Abstract

Background: Early-life stress is associated with alterations in telomere length, a marker of accumulated stress and aging, and a risk factor for psychiatric disorders. Nonhuman primate maternal variable foraging demand (VFD) is a validated early-life stress model, resulting in anxiety- and depressive-like symptoms in offspring. Previous studies reported increased plasma glucagon-like peptide 1 (pGLP-1) along with insulin resistance in this model. We investigated whether VFD rearing related to adult telomere length and to these neuroendocrine markers.

Methods: Adult leukocyte telomere length was measured in VFD-reared (12 males, 13 females) and non-VFD-reared (9 males, 26 females) bonnet macaques. Associations between adult telomere length and adolescent fasting pGLP-1 or insulin resistance in VFD-reared versus non-VFD-reared groups were examined using regression modeling, controlling for sex, weight, and age.

Results: VFD subjects had relatively longer telomeres than non-VFD subjects (p = .017), and females relatively longer than males (p = .0004). Telomere length was positively associated with pGLP-1 (p = .0009) and with reduced insulin sensitivity (p < .0001) in both sexes, but not as a function of rearing group.

Conclusions: Unexpectedly, VFD was associated with longer adult telomere length. Insulin resistance may lead to higher pGLP-1 levels in adolescence, which could protect telomere length in VFD offspring as adults. Associations between adult telomere length and adolescent insulin resistance and high pGLP-1 may reflect an adaptive, compensatory response after early-life stress exposure.

Keywords: Adaptive calibration; Adversity; Early-life stress; Insulin; Maltreatment; Telomere; pGLP-1.