Aging is a heterogeneous process across individual cells

Datum

03.11.2017

Zeit

16:00 - 17:00

Sprecher

Nikolay Ninov, Sharan Janjuha

Zugehörigkeit

Predoc

Sprache

en

Hauptthema

Biologie

Andere Themen

Biologie, Medizin

Host

Nikolay Ninov

Beschreibung

Individual organisms age at different rates, however, it remains unclear how aging alters the properties of individual cells, including their capacity for renewal. Using single-cell approaches, here we show that zebrafish pancreatic beta-cells exhibit a heterogeneous upregulation of transcripts involved in endoplasmic reticulum stress, inhibition of growth factor signaling and inflammation, including NF-kB signaling with age. We link the heterogeneity in NF-kB signaling activation in beta-cells to differences in their proliferation and gene-expression. In younger islets, beta-cells with higher NF-kB-activity proliferate less compared to their neighbors with lower activity, and upregulate prematurely socs2, a gene naturally expressed in aged beta-cells. In turn, socs2 can inhibit beta-cell proliferation in a cell-autonomous manner. NF-kB activation correlates with the recruitment of tnfα-expressing immune cells, pointing towards a role for the islet microenvironment in this activity. We propose that the renewal potential of beta-cells declines in a heterogeneous manner with age and identify NF-kB signaling as a marker of this heterogeneity. The identification of reliable markers of beta-cell aging will be key to enable early interventions for diabetes prevention, as well as for promoting beta-cell repair and renewal.

Links

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Letztmalig verändert: 03.11.2017, 08:47:09