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Multi‐generational silencing dynamics control cell aging
Author(s) -
Hao Nan,
Li Yang,
Jin Meng,
O'Laughlin Ricky,
Tsimring Lev,
Pillus Lorraine,
Hasty Jeff
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.614.6
Subject(s) - gene silencing , biology , microbiology and biotechnology , heterochromatin , ageing , genetics , chromatin , dna , gene
Cell aging is a universal biological phenomenon, but mechanisms that regulate aging remain unclear. Using novel microfluidic and imaging technologies, we tracked the replicative aging of single yeast cells and found a dramatic loss of heterochromatin silencing leading to cell aging and death. The dynamics of silencing loss during aging can be dissected into an early phase with sporadic silencing loss, followed by sustained silencing loss preceding cell death. Although the length of the later phase is relatively constant, the length of the early phase is highly variable among cells and largely determines lifespan. The intermittent silencing dynamics during the early phase depends on a conserved histone deacetylase Sir2 and is important for longevity, whereas either sustained silencing or loss of silencing shortens lifespan. These findings reveal that the temporal dynamics of key molecular processes can directly influence cell aging.