T cells with dysfunctional mitochondria induce multimorbidity and premature senescence.
Science
; 368(6497): 1371-1376, 2020 06 19.
Article
em En
| MEDLINE
| ID: mdl-32439659
ABSTRACT
The effect of immunometabolism on age-associated diseases remains uncertain. In this work, we show that T cells with dysfunctional mitochondria owing to mitochondrial transcription factor A (TFAM) deficiency act as accelerators of senescence. In mice, these cells instigate multiple aging-related features, including metabolic, cognitive, physical, and cardiovascular alterations, which together result in premature death. T cell metabolic failure induces the accumulation of circulating cytokines, which resembles the chronic inflammation that is characteristic of aging ("inflammaging"). This cytokine storm itself acts as a systemic inducer of senescence. Blocking tumor necrosis factor-α signaling or preventing senescence with nicotinamide adenine dinucleotide precursors partially rescues premature aging in mice with Tfam-deficient T cells. Thus, T cells can regulate organismal fitness and life span, which highlights the importance of tight immunometabolic control in both aging and the onset of age-associated diseases.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
/
Linfócitos T
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Senilidade Prematura
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Proteínas Mitocondriais
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Proteínas de Ligação a DNA
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Multimorbidade
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Mitocôndrias
Limite:
Animals
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article