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Related Concept Videos

Aging01:26

Aging

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Aging is a complex biological phenomenon influenced by various processes that affect cellular and systemic functions. Several prominent theories attempt to explain its mechanisms, highlighting cellular limitations, oxidative damage, and hormonal changes as central factors in aging.
Cellular Clock Theory
The cellular clock theory posits that the human lifespan is closely tied to the finite capacity of cells to divide, a phenomenon governed by telomeres, which are protective caps at the ends of...
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Mitochondria are eukaryotic cellular organelles that are known to produce energy through a process called oxidative phosphorylation. Besides their primary function, mitochondria are involved in various cellular processes, including cell growth, differentiation, signaling, metabolism, and senescence. Age-related changes cause a decline in mitochondrial quality and integrity due to increased mitochondrial mutations and oxidative damage. Thus, aging can severely impact mitochondrial functions,...
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Related Experiment Video

Updated: Nov 2, 2025

Protocol for the Differentiation of Human Induced Pluripotent Stem Cells into Mixed Cultures of Neurons and Glia for Neurotoxicity Testing
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Enhanced NRF2 expression mitigates the decline in neural stem cell function during aging.

Annadurai Anandhan1,2, Konner R Kirwan3, Mandi J Corenblum1

  • 1Department of Neurology, University of Arizona, Tucson, AZ, USA.

Aging Cell
|June 15, 2021
PubMed
Summary
This summary is machine-generated.

Augmenting NRF2 (nuclear factor erythroid 2-related factor 2) expression before middle age improved neural stem progenitor cell (NSPC) function and behavior. However, increasing NRF2 after this critical period showed no benefits.

Keywords:
NRF2agingneural stem cellsredoxsubventricular zone

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Area of Science:

  • Neuroscience
  • Aging Research
  • Stem Cell Biology

Background:

  • Aging significantly impacts neural stem progenitor cell (NSPC) biology, but the exact mechanisms remain unclear.
  • Previous research identified a critical period (CP) of NSPC decline during middle age, linked to reduced NRF2 (nuclear factor erythroid 2-related factor 2) expression.

Purpose of the Study:

  • To investigate if enhancing NRF2 expression can counteract the age-related decline in NSPC activity during the CP.
  • To determine the time-dependency of NRF2 modulation for maintaining NSPC function.

Main Methods:

  • NRF2 expression in rat subventricular zone (SVZ) NSPCs was upregulated using adeno-associated viral vectors (AAV-NRF2-eGFP).
  • Control vectors (AAV-eGFP) were used for comparison.
  • Vectors were administered before (11 months) or after (20 months) the identified CP.

Main Results:

  • Upregulating NRF2 before the CP (at 11 months) significantly improved behavioral functions, including olfactory discrimination and motor tasks.
  • NRF2 upregulation enhanced NSPC proliferation, self-renewal, neurogenesis, and migration to the olfactory bulb.
  • Increasing NRF2 after the CP (at 20 months) did not yield significant improvements in cellular or behavioral outcomes.

Conclusions:

  • NRF2 pathway modulation can support age-related NSPC function.
  • Activating NRF2 is time-dependent, with interventions being effective only before the critical period of decline.