Lipid peroxidation products induce carbonyl stress, mitochondrial dysfunction, and cellular senescence in human and murine cells
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View abstract on PubMed
Summary
This summary is machine-generated.Biogenic lipid enals, such as 4-HNE, trigger cellular senescence by damaging DNA and proteins. This process, termed biogenic lipid-induced senescence (BLIS), links oxidative stress to age-related diseases.
Area Of Science
- Biochemistry
- Cell Biology
- Gerontology
Background
- Lipid peroxidation generates electrophilic lipid enals.
- These molecules cause DNA and protein damage, inducing genotoxic and proteotoxic stress.
- Lipid enals accumulate in visceral fat during obesity and aging.
Purpose Of The Study
- To investigate if biogenic lipid enals act as endogenous inducers of cellular senescence.
- To explore the molecular mechanisms of lipid enal-induced senescence.
- To assess the therapeutic potential of targeting lipid enals in age-related pathologies.
Main Methods
- Treatment of IMR90 fibroblasts and murine adipose stem cells with lipid enals (4-HNE, 4-HHE, 4-ONE).
- Analysis of senescence markers (γH2AX, p53, p21<sup>Cip1</sup>), cytokine profiles, mitochondrial function, and apoptosis resistance.
- In vivo studies using L-carnosine as a 4-HNE scavenger in obese mice.
Main Results
- Lipid enals initiated cellular senescence, characterized by DNA damage, p53/p21<sup>Cip1</sup> activation, and altered cytokine secretion.
- Senescent cells exhibited mitochondrial dysfunction, altered nucleotide pools, and resistance to apoptosis.
- L-carnosine ameliorated lipid enal-induced senescence in vitro and reduced senescence biomarkers in vivo.
Conclusions
- Biogenic lipid enals are endogenous regulators of cellular senescence.
- Biogenic lipid-induced senescence (BLIS) provides a mechanistic link between oxidative stress and age-dependent diseases.
- Targeting lipid enals may offer therapeutic strategies for age-related conditions.
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