The Journal of biological chemistryAug 24, 2026

How ERα and SIRT1 signals help pterostilbene improve metabolism

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗

Updated Aug 25, 2026

Abstract

Pterostilbene (PTS) is a more potent metabolic regulator than resveratrol (RES).

PTS and RES activate estrogen receptor alpha (ERα), which is involved in the regulation of SIRT1 expression.
Both PTS and RES stabilize the interaction between ERα and SIRT1, preventing protein degradation.
PTS and RES enhance the stability of SIRT1 by blocking its ubiquitination.
Deacetylation of ERα by PTS and RES increases its ability to activate genes.
Inactivation of ERα specifically in skeletal muscle reduces the metabolic benefits observed with PTS.

Simplified

Pterostilbene (PTS), a more bioavailable analog of resveratrol (RES), is a promising natural metabolic regulator for improving metabolic health. The metabolic regulatory benefits of RES are believed to be associated with SIRT1 activation. However, the direct activation of SIRT1 by RES was proven to be an in vitro artifact. Here, we demonstrate that PTS is a more potent metabolic regulator than RES. More significantly, we have identified estrogen receptor α (ERα) as the intermediate signaling mediating SIRT1 expression by both RES and PTS. First, RES and PTS function as ERα agonists to stimulate Sirt1 transcription. Second, RES and PTS act as stabilizers of ERα-SIRT1 interaction, blocking ubiquitination and thereby enhancing their protein stability. Third, RES and PTS promote ERα deacetylation, subsequently increasing ERα transactivation. Finally, skeletal muscle-specific ERα knockout attenuates the metabolic regulatory benefits of PTS. Together, our study demonstrates that PTS is a more potent metabolic regulator than RES by activating the ERα/SIRT1 signaling.

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How ERα and SIRT1 signals help pterostilbene improve metabolism

Abstract

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