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<p>Mitochondrial homeostasis is majorly maintained through mitochondrial autophagy (mitophagy). Recent research highlights the region- and cell type-specific nature of mitophagy during brain aging; however, these dynamics have largely remained unexplored in living brains. To address this gap, we conducted two-photon mt-Keima imaging in somatosensory cortical neurons and astrocytes in behaving male mice across two age groups, including 2–3-month-old (early-aged) and 18–20-month-old (old-aged) mice. We show reduced mitophagy in both cell types during aging, and we consistently found a higher level of mitophagy in astrocytes compared to neurons at the same age, in both age groups. Pharmacological augmentation of NAD<sup>+</sup>, a pivotal metabolite that induces mitophagy but normally declines in the aging brain, increased cellular mitophagy in both neurons and astrocytes in old-aged male mice at the dose and method of administration tested. Collectively, our data support an age-dependent reduction of mitophagy in neurons and astrocytes, at least in mouse somatosensory cortex, while NAD<sup>+</sup> repletion offsets such reduction.</p>

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Two-photon in vivo imaging reveals cell type-specific mitophagy dynamic changes in mouse somatosensory cortex during aging

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月26日

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  • Beatriz Escobar-Doncel,
  • Xiaoyi Zhang,
  • Åsne Ljøstad,
  • Mario Fernández de la Puebla,
  • Shreyas Balachandra Rao,
  • Synnøve Algrøy Fjeldstad,
  • Maja Tvedt Dahle,
  • Mahmood Amiry-Moghaddam,
  • Magnar Bjørås,
  • Evandro Fei Fang,
  • Wannan Tang

摘要

Mitochondrial homeostasis is majorly maintained through mitochondrial autophagy (mitophagy). Recent research highlights the region- and cell type-specific nature of mitophagy during brain aging; however, these dynamics have largely remained unexplored in living brains. To address this gap, we conducted two-photon mt-Keima imaging in somatosensory cortical neurons and astrocytes in behaving male mice across two age groups, including 2–3-month-old (early-aged) and 18–20-month-old (old-aged) mice. We show reduced mitophagy in both cell types during aging, and we consistently found a higher level of mitophagy in astrocytes compared to neurons at the same age, in both age groups. Pharmacological augmentation of NAD+, a pivotal metabolite that induces mitophagy but normally declines in the aging brain, increased cellular mitophagy in both neurons and astrocytes in old-aged male mice at the dose and method of administration tested. Collectively, our data support an age-dependent reduction of mitophagy in neurons and astrocytes, at least in mouse somatosensory cortex, while NAD+ repletion offsets such reduction.