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Maternal nutrient restriction in baboon programs later-life cellular growth and respiration of cultured skin fibroblasts: a potential model for the study of aging-programming interactions

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Abstract

Compelling data exist for programming of chronic later-life diseases and longevity by perinatal developmental programming challenges. Understanding mechanisms by which life course health trajectory and longevity are set is fundamental to understanding aging. Appropriate approaches are needed to determine programming effects on cellular function. We have developed a baboon model in which control mothers eat ad libitum while a second group eat 70% of the global diet fed controls, leading to male and female offspring intrauterine growth restriction (IUGR). We have shown that IUGR suffer from acceleration of several age-related physiological declines. Here, we report on a skin-derived fibroblast model with potential relevance for mechanistic studies on how IUGR impacts aging. Fibroblasts were cultured from the skin biopsies taken from adult baboons from control and IUGR cohorts. IUGR-derived fibroblasts grew in culture less well than controls and those derived from male, but not female, IUGR baboons had a significant reduction in maximum respiration rate compared to control-derived fibroblasts. We also show that relative levels of several mitochondrial protein subunits, including NDUFB8 and cytochrome c oxidase subunit IV, were reduced in IUGR-derived fibroblasts even after serial passaging in culture. The lower levels of electron transport system components provide potential mechanisms for accelerated life course aging in the setting of programmed IUGR. This observation fits with the greater sensitivity of males compared with females to many, but not all, outcomes in response to programming challenges. These approaches will be powerful in the determination of programming-aging interactions.

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Abbreviations

ECAR:

Extracellular acidification rate

FCCP:

Carbonyl cyanide-p-trifluoromethoxyphenylhydrazone

GH:

Growth hormone

IGF1:

Insulin-like growth factor 1

IUGR:

Intrauterine growth restriction

OCR:

Oxygen consumption rate

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Funding

During the preparation of this manuscript, ABS received support from grants from the National Institute of Health (R01 AG050797 and R01 AG057431), the San Antonio Nathan Shock Center and Claude A. Pepper Center, and from the Geriatric Research, Education and Clinical Center of the South Texas Veterans Health Care System. This material is the result of work supported with resources and the use of facilities at South Texas Veterans Health Care System, San Antonio, TX. The contents do not represent the views of the US Department of Veterans Affairs or the US Government. Baboons in this study were generated under 1 R24 RR021367-01 (PWN).

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Authors and Affiliations

  1. Geriatric Research, Education and Clinical Center, South Texas Veterans Health Care System, San Antonio, TX, USA

    Adam B. Salmon

  2. The Sam and Ann Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA

    Adam B. Salmon & Jonathan Dorigatti

  3. Department of Molecular Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA

    Adam B. Salmon

  4. Department of Animal Science, University of Wyoming, Laramie, WY, USA

    Hillary F. Huber, Cun Li & Peter W. Nathanielsz

  5. Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, TX, USA

    Hillary F. Huber, Cun Li & Peter W. Nathanielsz

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  1. Adam B. Salmon
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  2. Jonathan Dorigatti
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  3. Hillary F. Huber
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  4. Cun Li
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  5. Peter W. Nathanielsz
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Correspondence to Adam B. Salmon.

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Salmon, A.B., Dorigatti, J., Huber, H.F. et al. Maternal nutrient restriction in baboon programs later-life cellular growth and respiration of cultured skin fibroblasts: a potential model for the study of aging-programming interactions. GeroScience 40, 269–278 (2018). https://doi.org/10.1007/s11357-018-0024-0

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