Journal Article DZNE-2026-00726

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HTZ-1/H2A.Z expression sustains transcriptional programs that regulate Caenorhabditis elegans lifespan.

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2026
Elsevier Science Amsterdam [u.a.]

Mechanisms of ageing and development 232, 112217 () [10.1016/j.mad.2026.112217]

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Abstract: Animal lifespan depends on coordinated gene expression networks that regulate metabolic adaptation, proteostasis, and stress resilience in response to environmental challenges. Histone variants are key regulators of chromatin dynamics, orchestrating nucleosome remodeling, DNA accessibility, and gene expression. While the role of histone H3.3 in aging and animal survival has been explored across model systems, the contribution of other replication-independent histone variants remains less well-defined. Here, we demonstrate that the evolutionarily conserved histone variant HTZ-1/H2A.Z is essential for organismal survival. In the nematode Caenorhabditis elegans, loss of HTZ-1/H2A.Z disrupts gene expression programs associated with longevity, including those activated in insulin/IGF-1 deficient daf-2 mutants and in mitochondrial Complex I deficient animals. Together, our findings show that HTZ-1/H2A.Z regulates gene expression programs that coordinate metabolic and proteostatic pathways, thereby fine-tuning stress responses and promoting lifespan in animals.

Keyword(s): Aging ; Caenorhabditis elegans ; Gene transcription ; HTZ-1/H2A.Z ; Insulin/IGF-1/DAF-2 signaling ; Longevity ; Metabolism

Classification:

Contributing Institute(s):
  1. Aging and Neurodegeneration (AG Bano)
  2. Translational Biogerontology (AG Ehninger)
  3. Population & Clinical Neuroepidemiology (AG Aziz)
  4. Clinical Single Cell Omics (CSCO) / Systems Medicine (AG Schultze)
  5. Platform for Single Cell Genomics and Epigenomics (PRECISE)
  6. Mathematics, statistics and informatics methods for support of population studies and clinical research (AG Schmid Bonn)
  7. Immunogenomics and Neurodegeneration (AG Beyer)
Research Program(s):
  1. 351 - Brain Function (POF4-351) (POF4-351)
  2. 352 - Disease Mechanisms (POF4-352) (POF4-352)
  3. 354 - Disease Prevention and Healthy Aging (POF4-354) (POF4-354)
  4. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

Appears in the scientific report 2026
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Medline ; Creative Commons Attribution CC BY 4.0 ; OpenAccess ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Essential Science Indicators ; IF >= 5 ; JCR ; NationallizenzNationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection
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Document types > Articles > Journal Article
Institute Collections > BN DZNE > BN DZNE-AG Schultze
Institute Collections > BN DZNE > BN DZNE-AG Ehninger
Institute Collections > BN DZNE > BN DZNE-AG Beyer
Institute Collections > BN DZNE > BN DZNE-PRECISE
Institute Collections > BN DZNE > BN DZNE-AG Aziz
Institute Collections > BN DZNE > BN DZNE-AG Bano
BN DZNE-AG Schmid Bonn
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 Record created 2026-07-08, last modified 2026-07-16