Senescence Driven by Mitochondrial Alterations [Mar. 5, 2025]

Apoptotic stress causes mtDNA release during senescence and drives the SASP
Stella Victorelli, et. al., Nature, 2023.
Apoptosis is triggered by widespread mitochondrial outer membrane permeabilization (MOMP), whereas in cellular senescence, sublethal minority MOMP occurs in a subset of mitochondria, releasing mtDNA into the cytosol and inducing SASP-driven inflammation.

Highlighted technique: When apoptotic stress increases the permeability of the mitochondrial outer membrane, cytochrome c is released into the cytoplasm, making it a key indicator of MOMP. In this study, MOMP is assessed by co-staining the mitochondrial outer membrane protein TOM20 and cytochrome c, followed by high-resolution analysis.

Mitochondrial fatty acid oxidation drives senescence
Shota Yamauchi, et. al., Science Advances, 2024.
DNA damage triggers the phosphorylation of BNIP3, a mitochondrial membrane protein, leading to an increase in cristae and enhanced FAO. This, in turn, promotes histone acetylation and induces the expression of the senescence marker p16.

Highlighted technique: This study assessed senescence using multiple markers, including p16 expression and SA-βgal activity. While other markers changed, γH2AX did not, reinforcing the widely accepted notion that no single marker defines senescence. Thus, multiple indicators are needed to assess senescence.

Senescent glia link mitochondrial dysfunction and lipid accumulation
China Byrnsn, et. al., Nature, 2024.
In the Drosophila brain, AP1+ senescent glia arise from neuronal mitochondrial dysfunction, promote lipid accumulation in non-senescent glia, and increase senescence markers. While suppressing AP1+ activity extends lifespan, it also exacerbates oxidative damage in the brain, leaving neuronal mitochondrial dysfunction unresolved, possibly due to reduced lipid accumulation.

Highlighted technique: In recent years, many studies have reported a link between senescence and Lipid droplets (LD). LDs are detected with BODIPY 493/503 as used in this paper. We also offer Lipi-Dye, a dye specifically designed for LD detection with high intracellular retention. With its range of color variations, it can be a valuable tool for researchers studying LD.