Integrated multi-omics analysis of brain aging in female nonhuman primates reveals altered signaling pathways relevant to age-related disorders

Laura A. Cox; Sobha Puppala; Jeannie Chan; Kip D. Zimmerman; Zeeshan Hamid; Isaac Ampong; Hillary F. Huber; Ge Li; Avinash Y.L. Jadhav; Benlian Wang; Cun Li; Mark G. Baxter; Carol Shively; Geoffrey D. Clarke; Thomas C. Register; Peter W. Nathanielsz; Michael Olivier

doi:10.1016/j.neurobiolaging.2023.08.009

Integrated multi-omics analysis of brain aging in female nonhuman primates reveals altered signaling pathways relevant to age-related disorders

Laura A. Cox, Sobha Puppala, Jeannie Chan, Kip D. Zimmerman, Zeeshan Hamid, Isaac Ampong, Hillary F. Huber, Ge Li, Avinash Y.L. Jadhav, Benlian Wang, Cun Li, Mark G. Baxter, Carol Shively, Geoffrey D. Clarke, Thomas C. Register, Peter W. Nathanielsz, Michael Olivier

Research output: Contribution to journal › Article › peer-review

2 Scopus citations

Abstract

The prefrontal cortex (PFC) has been implicated as a key brain region responsible for age-related cognitive decline. Little is known about aging-related molecular changes in PFC that may mediate these effects. To date, no studies have used untargeted discovery methods with integrated analyses to determine PFC molecular changes in healthy female primates. We quantified PFC changes associated with healthy aging in female baboons by integrating multiple omics data types (transcriptomics, proteomics, metabolomics) from samples across the adult age span. Our integrated omics approach using unbiased weighted gene co-expression network analysis to integrate data and treat age as a continuous variable, revealed highly interconnected known and novel pathways associated with PFC aging. We found Gamma-aminobutyric acid (GABA) tissue content associated with these signaling pathways, providing 1 potential biomarker to assess PFC changes with age. These highly coordinated pathway changes during aging may represent early steps for aging-related decline in PFC functions, such as learning and memory, and provide potential biomarkers to assess cognitive status in humans.

Original language	English
Pages (from-to)	109-119
Number of pages	11
Journal	Neurobiology of Aging
Volume	132
DOIs	https://doi.org/10.1016/j.neurobiolaging.2023.08.009
State	Published - Dec 2023
Externally published	Yes

Keywords

Brain prefrontal cortex
Integrated omics
Nonhuman primate
Normal aging

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10.1016/j.neurobiolaging.2023.08.009

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Cox, L. A., Puppala, S., Chan, J., Zimmerman, K. D., Hamid, Z., Ampong, I., Huber, H. F., Li, G., Jadhav, A. Y. L., Wang, B., Li, C., Baxter, M. G., Shively, C., Clarke, G. D., Register, T. C., Nathanielsz, P. W., & Olivier, M. (2023). Integrated multi-omics analysis of brain aging in female nonhuman primates reveals altered signaling pathways relevant to age-related disorders. Neurobiology of Aging, 132, 109-119. https://doi.org/10.1016/j.neurobiolaging.2023.08.009

@article{aceb1e6fc6cb452cb67348431f24646c,

title = "Integrated multi-omics analysis of brain aging in female nonhuman primates reveals altered signaling pathways relevant to age-related disorders",

abstract = "The prefrontal cortex (PFC) has been implicated as a key brain region responsible for age-related cognitive decline. Little is known about aging-related molecular changes in PFC that may mediate these effects. To date, no studies have used untargeted discovery methods with integrated analyses to determine PFC molecular changes in healthy female primates. We quantified PFC changes associated with healthy aging in female baboons by integrating multiple omics data types (transcriptomics, proteomics, metabolomics) from samples across the adult age span. Our integrated omics approach using unbiased weighted gene co-expression network analysis to integrate data and treat age as a continuous variable, revealed highly interconnected known and novel pathways associated with PFC aging. We found Gamma-aminobutyric acid (GABA) tissue content associated with these signaling pathways, providing 1 potential biomarker to assess PFC changes with age. These highly coordinated pathway changes during aging may represent early steps for aging-related decline in PFC functions, such as learning and memory, and provide potential biomarkers to assess cognitive status in humans.",

keywords = "Brain prefrontal cortex, Integrated omics, Nonhuman primate, Normal aging",

author = "Cox, {Laura A.} and Sobha Puppala and Jeannie Chan and Zimmerman, {Kip D.} and Zeeshan Hamid and Isaac Ampong and Huber, {Hillary F.} and Ge Li and Jadhav, {Avinash Y.L.} and Benlian Wang and Cun Li and Baxter, {Mark G.} and Carol Shively and Clarke, {Geoffrey D.} and Register, {Thomas C.} and Nathanielsz, {Peter W.} and Michael Olivier",

note = "Publisher Copyright: {\textcopyright} 2023 Elsevier Inc.",

year = "2023",

month = dec,

doi = "10.1016/j.neurobiolaging.2023.08.009",

language = "English",

volume = "132",

pages = "109--119",

journal = "Neurobiology of Aging",

issn = "0197-4580",

publisher = "Elsevier Inc.",

}

Cox, LA, Puppala, S, Chan, J, Zimmerman, KD, Hamid, Z, Ampong, I, Huber, HF, Li, G, Jadhav, AYL, Wang, B, Li, C, Baxter, MG, Shively, C, Clarke, GD, Register, TC, Nathanielsz, PW & Olivier, M 2023, 'Integrated multi-omics analysis of brain aging in female nonhuman primates reveals altered signaling pathways relevant to age-related disorders', Neurobiology of Aging, vol. 132, pp. 109-119. https://doi.org/10.1016/j.neurobiolaging.2023.08.009

TY - JOUR

T1 - Integrated multi-omics analysis of brain aging in female nonhuman primates reveals altered signaling pathways relevant to age-related disorders

AU - Cox, Laura A.

AU - Puppala, Sobha

AU - Chan, Jeannie

AU - Zimmerman, Kip D.

AU - Hamid, Zeeshan

AU - Ampong, Isaac

AU - Huber, Hillary F.

AU - Li, Ge

AU - Jadhav, Avinash Y.L.

AU - Wang, Benlian

AU - Li, Cun

AU - Baxter, Mark G.

AU - Shively, Carol

AU - Clarke, Geoffrey D.

AU - Register, Thomas C.

AU - Nathanielsz, Peter W.

AU - Olivier, Michael

PY - 2023/12

Y1 - 2023/12

N2 - The prefrontal cortex (PFC) has been implicated as a key brain region responsible for age-related cognitive decline. Little is known about aging-related molecular changes in PFC that may mediate these effects. To date, no studies have used untargeted discovery methods with integrated analyses to determine PFC molecular changes in healthy female primates. We quantified PFC changes associated with healthy aging in female baboons by integrating multiple omics data types (transcriptomics, proteomics, metabolomics) from samples across the adult age span. Our integrated omics approach using unbiased weighted gene co-expression network analysis to integrate data and treat age as a continuous variable, revealed highly interconnected known and novel pathways associated with PFC aging. We found Gamma-aminobutyric acid (GABA) tissue content associated with these signaling pathways, providing 1 potential biomarker to assess PFC changes with age. These highly coordinated pathway changes during aging may represent early steps for aging-related decline in PFC functions, such as learning and memory, and provide potential biomarkers to assess cognitive status in humans.

AB - The prefrontal cortex (PFC) has been implicated as a key brain region responsible for age-related cognitive decline. Little is known about aging-related molecular changes in PFC that may mediate these effects. To date, no studies have used untargeted discovery methods with integrated analyses to determine PFC molecular changes in healthy female primates. We quantified PFC changes associated with healthy aging in female baboons by integrating multiple omics data types (transcriptomics, proteomics, metabolomics) from samples across the adult age span. Our integrated omics approach using unbiased weighted gene co-expression network analysis to integrate data and treat age as a continuous variable, revealed highly interconnected known and novel pathways associated with PFC aging. We found Gamma-aminobutyric acid (GABA) tissue content associated with these signaling pathways, providing 1 potential biomarker to assess PFC changes with age. These highly coordinated pathway changes during aging may represent early steps for aging-related decline in PFC functions, such as learning and memory, and provide potential biomarkers to assess cognitive status in humans.

KW - Brain prefrontal cortex

KW - Integrated omics

KW - Nonhuman primate

KW - Normal aging

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U2 - 10.1016/j.neurobiolaging.2023.08.009

DO - 10.1016/j.neurobiolaging.2023.08.009

M3 - Article

C2 - 37797463

AN - SCOPUS:85172882268

SN - 0197-4580

VL - 132

SP - 109

EP - 119

JO - Neurobiology of Aging

JF - Neurobiology of Aging

ER -

Integrated multi-omics analysis of brain aging in female nonhuman primates reveals altered signaling pathways relevant to age-related disorders

Abstract

Keywords

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