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.

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. New Publications: Ito TK, Yokoyama M, Yoshida Y, Nojima A, Kassai H, Oishi K, Okada S, Kinoshita D, Kobayashi Y, Fruttiger M, Aiba A, Minamino T. A crucial role for CDC42 in senescence-associated inflammation and atherosclerosis. PLoS One. 2014; 9(7):e102186. Paul C, Robaire B. Impaired function of the blood-testis barrier during aging is preceded by a decline in cell adhesion proteins and GTPases. PLoS One. 2013; 8(12):e84354. Hunt NJ, Rodriguez ML, Waters KA, Machaalani R. Changes in orexin (hypocretin) neuronal expression with normal aging in the human hypothalamus. Neurobiol Aging. 2015; 36(1):292-300.

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 Domain	Activation Assay	Catalog No.
Pak1 p21-binding domain (PAK1-PBD)	Rac1 Activation Assay Kit Rac1/Cdc42 Activation Assay Kit Rac2 Activation Assay Kit Cdc42 Activation Assay Kit	17-283 17-441 17-369 17-286
Rhotekin Rho-binding domain (Rhotekin-RBD)	Rho Activation Assay Kit	17-294
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 RalB Activation Assay	17-300 17-439

Hallmarks of Aging
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