Reposted by Katie Pickup
In their Review, Anastasia Zhurikhina, Maia Kirkegaard, Alberto Guarnieri and Hanna Martens discuss the mechanisms and mechanics of #aging.
journals.biologists.com/jcs/article/...
![Schematic showing age-associated disruption of the ECM–cytoskeleton–nucleus mechanotransduction axis. Top, in young cells (i.e. cells from young donors or animals, or early-passage cultures with normal proliferative capacity and morphology), ECM engagement promotes activation and clustering of αβ integrins and assembly of focal adhesions (FAs) containing talin, vinculin, paxillin, FAK and Src. These structures couple the ECM to aligned actin stress fibers and the perinuclear actin cap, enabling force transmission to the nucleus through the LINC complex [SUN1 and/or SUN2 (SUN1/2) with nesprin] and an intact nuclear lamina. PIEZO1-mediated Ca2+ influx promotes FAK–Src and PI3K–AKT signaling and further supports mechanosensitive transcriptional programs mediated by the transcription factors (TFs) YAP/TAZ–TEAD, MRTF–SRF, β-catenin and KLF2 and KLF4 (KLF2/4), impacting genes involved in nuclear envelope (NE) integrity, cytoskeletal integrity, osteogenesis and vasculoprotection, respectively. Bottom, in aged and senescent cells (i.e. cells from aged donors or animals, or replicatively or stress-induced senescent cultures, as defined in the cited studies by stable proliferative arrest together with one or more established senescence markers), integrin composition and focal adhesion assembly are altered, actin organization is disrupted and microtubules (MTs) become excessively stabilized. Reduced SUN2 expression and loss of lamin B1 weaken nucleo-cytoskeletal coupling, de-repress heterochromatin and reduce PIEZO1 expression. Together, these changes blunt mechanosensitive transcriptional responses and impair force transmission from the ECM to the genome. Created in BioRender by Guarnieri, A., 2026. https://BioRender.com/9lv8rls. This figure was sublicensed under CC-BY 4.0 terms.](https://cdn.bsky.app/img/feed_thumbnail/plain/did:plc:mmkxrjpuoekx6rvbec4bh6nf/bafkreif5ong5qvlytrlvxg3xezswn5ajkpgtbewpe4mmxjifcqv3657p2m)
Katie Pickup
@katiepickup.bsky.social
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🧬 Reviews Editor @biologists.bsky.social 👩🏻🔬 PhD epigenetics & differentiation @uoe-igc.bsky.social Views my own | she/her
