TY - JOUR
T1 - Marmoset as a model to study kidney changes associated with aging
AU - Lee, Hak Joo
AU - Gonzalez, Olga
AU - Dick, Edward J.
AU - Donati, Andrew
AU - Feliers, Denis
AU - Choudhury, Goutam Ghosh
AU - Ross, Corinna
AU - Venkatachalam, Manjeri
AU - Tardif, Suzette D
AU - Kasinath, Balakuntalam S
N1 - Publisher Copyright:
© The Author(s) 2018.
PY - 2019/2/15
Y1 - 2019/2/15
N2 - We evaluated whether the marmoset, a nonhuman primate, can serve as a good model to study aging-related changes in the kidney by employing healthy young and aged marmosets of both sexes. Aging was associated with glomerulosclerosis, interstitial fibrosis, and arteriolosclerosis in both sexes; correspondingly, the content of matrix proteins was increased. Functionally, aging resulted in an increase in urinary albumin and protein excretion. There was a robust correlation between markers of fibrosis and functional changes. We explored signaling pathways as potential mechanistic events. Aging in males, but not in females, was associated with reduced renal cortical activity of AMP-activated protein kinase (AMPK) and a trend toward activation of mechanistic target of rapamycin complex 1 (mTORC1); upstream of AMPK and mTORC1, Akt and IGF-1 receptor were activated. In both sexes, aging promoted kidney activation of transforming growth factor β-1 signaling pathway. While the expression of cystathionine β-synthase (CBS), an enzyme involved hydrogen sulfide (H2S) synthesis, was reduced in both aged males and females, decreased H2S generation was seen in only males. Our studies show that the marmoset is a valid model to study kidney aging; some of the signaling pathways involved in renal senescence differ between male and female marmosets.
AB - We evaluated whether the marmoset, a nonhuman primate, can serve as a good model to study aging-related changes in the kidney by employing healthy young and aged marmosets of both sexes. Aging was associated with glomerulosclerosis, interstitial fibrosis, and arteriolosclerosis in both sexes; correspondingly, the content of matrix proteins was increased. Functionally, aging resulted in an increase in urinary albumin and protein excretion. There was a robust correlation between markers of fibrosis and functional changes. We explored signaling pathways as potential mechanistic events. Aging in males, but not in females, was associated with reduced renal cortical activity of AMP-activated protein kinase (AMPK) and a trend toward activation of mechanistic target of rapamycin complex 1 (mTORC1); upstream of AMPK and mTORC1, Akt and IGF-1 receptor were activated. In both sexes, aging promoted kidney activation of transforming growth factor β-1 signaling pathway. While the expression of cystathionine β-synthase (CBS), an enzyme involved hydrogen sulfide (H2S) synthesis, was reduced in both aged males and females, decreased H2S generation was seen in only males. Our studies show that the marmoset is a valid model to study kidney aging; some of the signaling pathways involved in renal senescence differ between male and female marmosets.
KW - Extracellular matrix
KW - Fibrosis
KW - Glomerulus
KW - Primates
KW - Signaling
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U2 - 10.1093/gerona/gly237
DO - 10.1093/gerona/gly237
M3 - Article
C2 - 30321310
AN - SCOPUS:85060339636
SN - 1079-5006
VL - 74
SP - 315
EP - 324
JO - Journals of Gerontology - Series A Biological Sciences and Medical Sciences
JF - Journals of Gerontology - Series A Biological Sciences and Medical Sciences
IS - 3
ER -