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The human microbiota begins developing at birth and undergoes continual change as we age. Infancy marks a critical period of microbial sensitivity, offering a “window of opportunity” during which beneficial microbes help mature the immune system. By age three, children typically develop a more stable and diverse microbial community. Newborns acquire microbes from their immediate environment; vaginal delivery favors maternal vaginal microbes, while cesarean births favor microbes from...
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The gut–brain axis is a bidirectional communication system that connects the gastrointestinal tract and the brain. This interaction is mediated through multiple pathways, including the vagus nerve, hormonal signals, immune responses, and chemical messengers produced by gut microbes.Microbial Contributions to Brain FunctionGut microbiota contributes significantly to brain function by producing neuroactive compounds. These include neuroactive compounds that influence neurotransmitters such...
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Lactoferrin ameliorates cognitive impairment in D-galactose-induced aging mice by regulating the PI3K/Akt/mTOR

Mengqi Wang1, Yi Wang2, Xin Wang1

  • 1College of Food Science and Engineering, Tianjin University of Science & Technology, Tianjin 300457, China.

International Journal of Biological Macromolecules
|April 13, 2025
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Lactoferrin (LF) supplementation improved cognitive function and physical health in aging mice by reducing oxidative stress and inflammation. It also enhanced gut health and restored autophagy, suggesting LF as a potential anti-aging intervention.

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Area of Science:

  • Neuroscience
  • Gerontology
  • Microbiology

Background:

  • Oxidative stress and neuroinflammation contribute to brain aging.
  • Lactoferrin (LF) shows potential in mitigating these factors.
  • Mechanisms of LF's anti-aging effects, particularly on the brain, require further elucidation.

Purpose of the Study:

  • To investigate the efficacy of different doses of Lactoferrin (LF) in an aging mouse model.
  • To explore the underlying mechanisms of LF's effects on brain aging, including autophagy and the gut-brain axis.

Main Methods:

  • D-galactose induced brain aging in C57BL/6 mice.
  • Administration of varying Lactoferrin (LF) doses (50, 500, 2000 mg/kg).
  • Assessment of cognitive function, neuronal damage, intestinal barrier integrity, antioxidant/inflammatory markers, autophagy markers (Western blotting), and gut microbiome composition.

Main Results:

  • Lactoferrin (LF) (500 & 2000 mg/kg) restored body weight, mobility, and spatial memory.
  • LF attenuated hippocampal and intestinal barrier damage, increased antioxidant enzymes (SOD, GSH, CAT), and decreased inflammatory factors (IL-1β, IL-6, TNF-α).
  • LF modulated autophagy via the PI3K/Akt/m-TOR pathway and improved gut barrier function by regulating the Firmicutes/Bacteroidetes ratio and increasing short-chain fatty acids (SCFAs).

Conclusions:

  • Lactoferrin (LF) effectively alleviates D-galactose-induced brain aging in mice.
  • LF acts through regulating autophagy and the microbiome-gut-brain axis.
  • LF demonstrates significant anti-aging potential, with the 500 mg/kg dose showing cost-effectiveness.