The effect of the senescence-associated secretory phenotype (SASP) on glucose homeostasis in metabolic cells

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Abstract

Aim: Dysregulated glucose homeostasis is a hallmark of Type 2diabetes. A distinctive feature of ageing is the accumulation ofsenescent cells, defined as cells that have undergone irreversible lossof proliferative capacity. Characteristic of senescent cells is thesenescence-associated secretory phenotype (SASP) involving theproduction of factors which reinforce senescence arrest in neigh-bouring tissue environments. We hypothesise that SASP inducesmetabolic dysfunction in non-senescent cells, impairing glucosemetabolism and propagating insulin resistance. We sought todetermine the effect of SASP on glucose homeostasis in hepatic,adipose and skeletal muscle cell lines.
Methods: Human dermal fibroblasts were subjected to a geno-toxic dose of doxorubicin to induce senescence, confirmed using ab-galactosidase assay. Conditioned media containing SASP werecollected post 24h and 48h of inducing senescence and used at20% and 40% concentrations to treat AML-12 hepatocytes, 3T3-L1 adipocytes and C2C12 myocytes for 24h and 48h. Cells andmedia were collected and glucose and lipid concentrations weremeasured before and after the respective incubation periods.
Results: Cell media obtained from C2C12 myocytes exposed to40% SASP for 24h and 48h and AML-12 hepatocytes after 48hexhibited significantly higher concentrations of glucose in com-parison to control media (p < 0.0001, p < 0.05) suggesting areduced glucose uptake. Glucose utilisation remained unchanged in3T3-L1 cells.
Conclusion: Our data suggest an important role for SASP inaltering glucose homeostasis and identify SASP as a potentialmediator between ageing and the increase in age-related insulinresistance.

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Original languageEnglish
Article numberP208
Pages (from-to)93-94
Number of pages2
JournalDiabetic Medicine
Volume32
Issue numberSuppl.1
DOIs
Publication statusPublished - 11 Mar 2015
EventDiabetes UK Professional Conference 2015 - ExCel London, London, United Kingdom
Duration: 11 Mar 201513 Mar 2015

Bibliographic note

Special Issue: Abstracts of the Diabetes UK Professional Conference 2015, ExCeL London, 11–13 March 2015.

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