Sex-specific decline in prefrontal cortex mitochondrial bioenergetics in aging baboons correlates with walking speed.

Autor:	Adekunbi DA; Department of Molecular Medicine and Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, Texas, USA., Huber HF; Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, Texas, USA., Benavides GA; Department of Pathology, University of Alabama at Birmingham (UAB), and UAB Nathan Shock Center, Birmingham, AL, USA., Tian R; Department of Pathology, University of Alabama at Birmingham (UAB), and UAB Nathan Shock Center, Birmingham, AL, USA., Li C; Texas Pregnancy and Life-course Health Research Center, Department of Animal Science, University of Wyoming, Laramie, Wyoming, USA., Nathanielsz PW; Texas Pregnancy and Life-course Health Research Center, Department of Animal Science, University of Wyoming, Laramie, Wyoming, USA., Zhang J; Department of Pathology, University of Alabama at Birmingham (UAB), and UAB Nathan Shock Center, Birmingham, AL, USA., Darley-Usmar V; Department of Pathology, University of Alabama at Birmingham (UAB), and UAB Nathan Shock Center, Birmingham, AL, USA., Cox LA; Center for Precision Medicine, Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA., Salmon AB; Department of Molecular Medicine and Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, Texas, USA.; San Antonio Nathan Shock Center, University of Texas Health Science Center at San Antonio, Texas, USA.; Geriatric Research Education and Clinical Center, Audie L. Murphy Hospital, Southwest Veterans Health Care System, San Antonio, Texas, USA.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2024 Sep 24. Date of Electronic Publication: 2024 Sep 24.
DOI:	10.1101/2024.09.19.613684
Abstrakt:	Mitochondria play a crucial role in brain aging due to their involvement in bioenergetics, neuroinflammation and brain steroid synthesis. Mitochondrial dysfunction is linked to age-related neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease. We investigated changes in the activities of the electron transport chain (ETC) complexes in normally aging baboon brains and determined how these changes relate to donor sex, morning cortisol levels, and walking speed. Using a novel approach, we assessed mitochondrial bioenergetics from frozen prefrontal cortex (PFC) tissues from a large cohort (60 individuals) of well-characterized aging baboons (6.6-22.8 years, approximately equivalent to 26.4-91.2 human years). Aging was associated with a decline in mitochondrial ETC complexes in the PFC, which was more pronounced when activities were normalized for citrate synthase activity, suggesting that the decline in respiration is predominantly driven by changes in the specific activity of individual complexes rather than changes in mitochondrial number. Moreover, when donor sex was used as a covariate, we found that mitochondrial respiration was preserved with age in females, whereas males showed significant loss of ETC activity with age. Males had higher activities of each individual ETC complex and greater lactate dehydrogenase activity relative to females. Circulating cortisol levels correlated only with complex II-linked respiration in males. We also observed a robust positive predictive relationship between walking speed and respiration linked to complexes I, III, and IV in males but not in females. This data reveals a previously unknown link between aging and bioenergetics across multiple tissues linking frailty and bioenergetic function. This study highlights a potential molecular mechanism for sexual dimorphism in brain resilience and suggests that in males changes in PFC bioenergetics contribute to reduced motor function with age. Competing Interests: Competing Interest The authors declare no competing interest.
Databáze:	MEDLINE
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