Study type: In vivo/preclinical · Status: Verified against declared source

Late-life restoration of mitochondrial function reverses cardiac dysfunction in old mice.

eLife · 2020

Study scale: While the molecular mechanisms of proton leak are not fully understood, it has been shown that basal leak through mitochondrial inner membrane or around inner membrane proteins, and inducible leak through adenine nucleotide translocase (ANT) or uncoupling proteins (UCPs) contribute to mitochondrial proton leak (Jastroch et al., 2010).

Abstract only: Open source record

Product or molecular entity relationships

  • SS-31: Exact entity relationship. Legacy citation custody associates this source with the catalog record; no product-relevance conclusion is implied.

Plain-language verified summary

Question

1) There is a fundamental concern in that a similar improvement can be seen with SS-31 in young mice – which the authors show but do not discuss in Figure 1E.

Methods

(a) A histogram of the distribution of changes in glutathionylation levels in peptides from old control and old SS-31 treated hearts; n = 3 female mice per group, analyzed as described in the Materials and method section.

Scale or participants

While the molecular mechanisms of proton leak are not fully understood, it has been shown that basal leak through mitochondrial inner membrane or around inner membrane proteins, and inducible leak through adenine nucleotide translocase (ANT) or uncoupling proteins (UCPs) contribute to mitochondrial proton leak (Jastroch et al., 2010).

Key findings

Diastolic dysfunction is a prominent feature of cardiac aging in both mice and humans.

Limitations and uncertainty

To determine the effect of SS-31 treatment on mitochondrial respiration, we assessed the oxygen consumption rate (OCR) in isolated adult cardiomyocytes using the Seahorse Bioscience XF Cell Mito Stress Test assay.

Verified against declared source. Verification is limited to the declared source and review scope. It does not mean independent replication or establish efficacy, safety, or suitability.