TY - JOUR
T1 - Hydrogen sulfide ameliorates aging-associated changes in the kidney
AU - Lee, Hak Joo
AU - Feliers, Denis
AU - Barnes, Jeffrey L.
AU - Oh, Sae
AU - Choudhury, Goutam Ghosh
AU - Diaz, Vivian
AU - Galvan, Veronica
AU - Strong, Randy
AU - Nelson, James
AU - Salmon, Adam
AU - Kevil, Christopher G.
AU - Kasinath, Balakuntalam S.
N1 - Funding Information:
Author contributions BSK, VG, JN, AS, and RS designed the study and analyzed the data. HJL, DF, SO, JB, and CK performed the experiments. All authors participated in data analysis and interpretation. BSK wrote the manuscript; all authors approved it.Funding informationA Pilot Study Grant to BSK from the Nathan Shock Center of Excellence in Basic Biology of Aging (NIH 1P30-AG013319) supported this work. This work was also supported by grants from the Veterans Affairs Biomedical Laboratory Research and Development Service (I01BX001340 to BSK, 5I01BX000926 to GGC, I01BX002211 to VG, II01BX001641 to RS) and the NIH (DK50190 to GGC, HL113303 to CGK, AG050797 to ABS). DF is supported by the American Heart Association (15GRNT25700363). GGC is a recipient of a Veterans Affairs Senior Research Career Scientist Award (IK6BX003611).
Funding Information:
The Institutional Animal Care and Utilization Committee of the University of Texas Health at San Antonio approved the animal studies. CGK has intellectual property for hydrogen sulfide measurement and biomarker and also has equity interest in Innolyzer LLC and Theravasc Inc. J.L.B. is a consultant and co-founder of Probetex, Inc. with ownership interests. All other authors declare that they have no conflict of interest.
Publisher Copyright:
© 2018, This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.
PY - 2018/4/1
Y1 - 2018/4/1
N2 - Aging is associated with replacement of normal kidney parenchyma by fibrosis. Because hydrogen sulfide (H2S) ameliorates kidney fibrosis in disease models, we examined its status in the aging kidney. In the first study, we examined kidney cortical H2S metabolism and signaling pathways related to synthesis of proteins including matrix proteins in young and old male C57BL/6 mice. In old mice, increase in renal cortical content of matrix protein involved in fibrosis was associated with decreased H2S generation and AMPK activity, and activation of insulin receptor (IR)/IRS-2-Akt-mTORC1-mRNA translation signaling axis that can lead to increase in protein synthesis. In the second study, we randomized 18–19 month-old male C57BL/6 mice to receive 30 μmol/L sodium hydrosulfide (NaHS) in drinking water vs. water alone (control) for 5 months. Administration of NaHS increased plasma free sulfide levels. NaHS inhibited the increase in kidney cortical content of matrix proteins involved in fibrosis and ameliorated glomerulosclerosis. NaHS restored AMPK activity and inhibited activation of IR/IRS-2-Akt-mTORC1-mRNA translation axis. NaHS inhibited age-related increase in kidney cortical content of p21, IL-1β, and IL-6, components of the senescence-associated secretory phenotype. NaHS abolished increase in urinary albumin excretion seen in control mice and reduced serum cystatin C levels suggesting improved glomerular clearance function. We conclude that aging-induced changes in the kidney are associated with H2S deficiency. Administration of H2S ameliorates aging-induced kidney changes probably by inhibiting signaling pathways leading to matrix protein synthesis.
AB - Aging is associated with replacement of normal kidney parenchyma by fibrosis. Because hydrogen sulfide (H2S) ameliorates kidney fibrosis in disease models, we examined its status in the aging kidney. In the first study, we examined kidney cortical H2S metabolism and signaling pathways related to synthesis of proteins including matrix proteins in young and old male C57BL/6 mice. In old mice, increase in renal cortical content of matrix protein involved in fibrosis was associated with decreased H2S generation and AMPK activity, and activation of insulin receptor (IR)/IRS-2-Akt-mTORC1-mRNA translation signaling axis that can lead to increase in protein synthesis. In the second study, we randomized 18–19 month-old male C57BL/6 mice to receive 30 μmol/L sodium hydrosulfide (NaHS) in drinking water vs. water alone (control) for 5 months. Administration of NaHS increased plasma free sulfide levels. NaHS inhibited the increase in kidney cortical content of matrix proteins involved in fibrosis and ameliorated glomerulosclerosis. NaHS restored AMPK activity and inhibited activation of IR/IRS-2-Akt-mTORC1-mRNA translation axis. NaHS inhibited age-related increase in kidney cortical content of p21, IL-1β, and IL-6, components of the senescence-associated secretory phenotype. NaHS abolished increase in urinary albumin excretion seen in control mice and reduced serum cystatin C levels suggesting improved glomerular clearance function. We conclude that aging-induced changes in the kidney are associated with H2S deficiency. Administration of H2S ameliorates aging-induced kidney changes probably by inhibiting signaling pathways leading to matrix protein synthesis.
KW - AMP-activated protein kinase
KW - Insulin receptor signaling
KW - Mechanistic target of rapamycin
KW - Protein chemistry
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U2 - 10.1007/s11357-018-0018-y
DO - 10.1007/s11357-018-0018-y
M3 - Article
C2 - 29717417
AN - SCOPUS:85046147195
VL - 40
SP - 163
EP - 176
JO - GeroScience
JF - GeroScience
SN - 2509-2715
IS - 2
ER -