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Altered Intercellular Communication

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Cells, as they age, show an increase in self-preserving signals that result in damage elsewhere. Altered intercellular communication with aging contributes to decline in tissue health.

Like the decline in stem cell renewal, the age-dependent changes in intercellular communication are integrated effects of the other hallmarks of aging. In particular, senescent cells trigger chronic inflammation that can further damage aging tissues.

The cdc42 GTPase pathway, in addition to the NF-κB pathway, has been shown to increase inflammation in senescent cells; in fact, knocking down cdc42 expression actually increases longevity in C. elegans. GTPases also integrate signals from cell-cell junctions, which may break down in aging tissues.

At an organ system level, the aging hypothalamus drives changes in neurohormone signaling, which in turn affects food intake and metabolism. Since the hypothalamus also regulates sleep cycles, these changes can inhibit DNA repair, exacerbating the aging phenotype.

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Hematopoetic Stem Cells (HSCs). Cdc42 and other pathways mediate signaling between aging HSCs and their niche (within the bone marrow). As HSCs age, they move further from the niche, lose cell polarity, and undergoe DNA damage. 
Did you know?
Inflammaging is defined as chronic, low-grade inflammation that is seen with aging. Inflammaging differs significantly from acute inflammation in that it is low-grade, controlled, asymptomatic, and persistent or chronic. Most age-related diseases share an inflammatory pathogenesis, making inflammatory pathogenesis, making Inflammaging a significant risk factor in our health as we age.

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Featured Solution: Small GTPase Activation Assays
The Small GTPase Activation Kits provide a quick and easy method for detecting active small GTPases. These assays isolate the active (GTP-bound) form of the protein with the binding domains of their downstream effectors immobilized on agarose beads. The isolated active GTPase is then detected by Western blot using a GTPase specific antibody. Complete kits include GTPase binding domain coupled to agarose beads, primary antibody, GDP, GTPγS, and buffer necessary to perform 20 or 30 pull-down assays.

GTPase Binding DomainActivation AssayCatalog No.
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Rac1/Cdc42 Activation Assay Kit
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Raf1 Ras-binding domain (Raf1-RBD) Ras Activation Assay Kit 17-218
RalGDS Rap1-binding domain (RalGDS-RBP) Rap1 Activation Assay Kit 17-321
Ral binding protein 1 (RalPB1-RBD) Ral Activation Assay Kit
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