Marmoset as a Model to Study Kidney Changes Associated With Aging

Lee, Hak‐Joo; González, Olga; Dick, Edward J.; Donati, Andrew; Féliers, Denis; Choudhury, Goutam Ghosh; Ross, Corinna N.; Venkatachalam, Manjeri A.; Tardif, Suzette D.; Kasinath, Balakuntalam S.

doi:10.1093/gerona/gly237

Cited by 22 publications

(15 citation statements)

References 54 publications

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“…Given their similarity in integrated albunemia scores and in associations with age and mortality, common marmosets might prove to be particularly useful research models for emergent physiological processes in humans. This adds to previous recommendations to better develop common marmosets as models for human aging (49,50). Notably, in this study, common marmosets appear to be much better models for emergent patterns of human physiology than rhesus macaques, which are more commonly used as research models.…”

Section: Discussionmentioning

confidence: 49%

An Emergent Integrated Aging Process Conserved Across Primates

Wey

Roberge

Legault

et al. 2019

The Journals of Gerontology: Series A

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Aging is a complex process emerging from integrated physiological networks. Recent work using principal component analysis (PCA) of multisystem biomarkers proposed a novel fundamental physiological process, “integrated albunemia,” which was consistent across human populations and more strongly associated with age and mortality risk than individual biomarkers. Here we tested for integrated albunemia and associations with age and mortality across six diverse nonhuman primate species and humans. PCA of 13 physiological biomarkers recovered in all species a primary axis of variation (PC1) resembling integrated albunemia, which increased with age in all but one species but was less predictive of mortality risk. Within species, PC1 scores were often reliably recovered with a minimal biomarker subset and usually stable between sexes. Even among species, correlations in PC1 structure were often strong, but the effect of phylogeny was inconclusive. Thus, integrated albunemia likely reflects an evolutionarily conserved process across primates and appears to be generally associated with aging but not necessarily with negative impacts on survival. Integrated albunemia is unlikely to be the only conserved emergent physiological process; our findings hence have implications both for the evolution of the aging process and of physiological networks more generally.

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Section: Discussionmentioning

confidence: 49%

An Emergent Integrated Aging Process Conserved Across Primates

Wey

Roberge

Legault

et al. 2019

The Journals of Gerontology: Series A

View full text Add to dashboard Cite

show abstract

“…On whole cell patch clamp, Cl − current was higher in hCLCA1 overexpressing cells indicating that the Cl − channel activity of TMEM16A was increased; Cl − current was completely inhibited by T16Ainh-A01, a selective TMEM16A inhibitor (Figure 3c). Overexpression of hCLCA1 resulted in increase in fibronectin, a kidney matrix protein that is increased in the aging kidney (Lee et al, 2018(Lee et al, , 2019 (Figure 3d).…”

Section: Chloride Channel Accessory 1 Overexpression Induces Mtorc1 and Augments Matrix Protein Contentmentioning

confidence: 99%

“…Recent findings indicate that gaseous molecules including H 2 S are important regulators of kidney function (Feliers et al, 2016;Kasinath et al, 2018). H 2 S is constitutively synthesized by the kidney (Lee et al, 2018(Lee et al, , 2019. Proximal tubule epithelial cells and podocytes synthesize H 2 S in vitro (Lee et al, ,2012(Lee et al, , , 2017.…”

Section: Effect Of H 2 S On Clca1-induced Changesmentioning

confidence: 99%

“…We have recently reported aging-associated changes in the kidneys of marmoset, a non-human primate (Lee et al, 2019). To study changes in kidney CLCA1 expression in aged marmosets, we performed immunoblotting on kidney cortical lysates from four male young (average age 3 years), four female young (average age 3 years), five aged male (average age 16 years), and five aged female marmosets (average age 16 years).…”

Section: Aged Marmosetsmentioning

confidence: 99%

“…Unabated tubulointerstitial fibrosis of the kidney is a major determinant of progressive loss of kidney function (Humphreys, 2018). These structural changes and proteinuria are evident in aging mice and aging non‐human primates (marmosets) (Bitzer & Wiggins, 2016; Lee et al, 2018, 2019; Sataranatarajan et al, 2012; Wu et al, 2010; Zheng et al, 2003). Current therapeutic approaches to inhibit kidney fibrosis are limited; while they may slow the progressive loss of kidney function, they are not able to halt it altogether.…”

Section: Introductionmentioning

confidence: 99%

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