Tier 2 — strong

SIRT6 in health and diseases: From molecular mechanisms to therapeutic prospects

Li YY, Wu JW, Wang Y, Song W, Shao D, Gao W, Yu H
Pharmacological Research 2025 Volume 221, article 107984

Bibliography

PubMed
PMID 41075996
DOI
10.1016/j.phrs.2025.107984
Funding
This study is supported by the funds from the Liaoning Provincial Science and Technology Program Project Declaration(2023JH2/101700122).
Competing interests
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Study snapshot

DesignNarrative review of the SIRT6 mechanism, disease, and therapeutic modulator literature.
ModelReview scope: SIRT6 regulatory networks and interactors; SIRT6 mechanisms in cancer, cardiovascular disease, diabetes, and neurodegenerative disorders; small-molecule SIRT6 activators and inhibitors, including pharmacological properties and therapeutic prospects.
SampleReference count not yet extracted from full-text — flag on paper page pending full-text incorporation.
InterventionNot applicable — literature synthesis.
DurationNot applicable — literature synthesis.
EndpointsSIRT6 regulatory network mapping; SIRT6 role in cancer initiation and progression; SIRT6 role in cardiovascular disease; SIRT6 role in diabetes and metabolic disease; SIRT6 role in neurodegenerative disease; Small-molecule SIRT6 activators and inhibitors — pharmacological profiles

What the study showed, in plain terms

This is the most recent comprehensive synthesis of the SIRT6 field, published open-access in October 2025 in Pharmacological Research. It covers everything: how SIRT6 works at the molecular level, what it does in cancer, cardiovascular disease, diabetes, and neurodegenerative disease, and where the drug development effort currently stands.

The review's most distinctive contribution is its dedicated coverage of small-molecule SIRT6 modulators — both activators and inhibitors — and their pharmacological properties. This is where recent SIRT6 reviews (Korotkov 2021, Li 2022, Guo 2022) had comparatively less detail. The Chen 2025 review is the current reference synthesis for the drug pipeline.

The review is a synthesis, not new data. It should be read as a well-organised map of what the field currently knows, not as a source of new experimental findings.

Key findings

  • Comprehensive current-state synthesis of SIRT6's three enzymatic activities (deacetylation, defatty-acylation, mono-ADP-ribosylation) and their substrates.
  • Dedicated coverage of SIRT6 in four major disease areas — cancer, cardiovascular disease, diabetes, and neurodegenerative disease — with underlying signalling mechanisms mapped for each.
  • The most detailed recent review coverage of small-molecule SIRT6 modulators, both activators (including MDL-800, MDL-811, UBCS039 and their derivatives) and inhibitors, with pharmacological profiles and preclinical status.
  • Open-access under Creative Commons — the review is freely accessible for readers wanting the full technical detail, which is useful context for the reader base of a supplement-focused Data Center.

What this study can and cannot tell us

Narrative review, not systematic. No pre-registered search protocol, no PRISMA methodology, no formal quality assessment. Reader should treat the synthesis as an informed roadmap, not a statistical summary of the evidence.

PubMed indexing was pending at the time this Data Center entry was created. This is a routine lag for very recent Elsevier papers and does not reflect on the paper's peer-review status. The paper is CrossRef-indexed and Creative Commons licensed. Update the metaobject with PMID and PubMed URL once available.

The full text has not yet been extracted for detailed cross-referencing against our other Data Center entries. Funding sources, competing interests, and specific reference count are flagged as pending until this is done. This is a housekeeping gap, not a red flag on the review itself.

As with all broad SIRT6 reviews, some sections lean on Chinese and East Asian clinical research groups where translation and independent replication are still developing. The review is fair-minded and does not overclaim, but the reader should approach specific disease claims (particularly in cardiovascular and diabetes sections) as syntheses of the underlying primary literature.

Related papers in the corpus

Tier 3
The many faces of SIRT6 in the retina and retinal pigment epithelium
Jie Cheng et al. · Frontiers in Cell and Developmental Biology · 2023
Tier 3
A rare human centenarian variant of SIRT6 enhances genome stability and interaction with Lamin A
Matthew Simon et al. · The EMBO Journal · 2022
Tier 2
SIRT6 Widely Regulates Aging, Immunity, and Cancer
Li Y et al. · Frontiers in Oncology · 2022
Tier 3
Sirt6 prevents the age-related decline of H2S through the control of one-carbon metabolism
Touitou N et al. · Proceedings of the National Academy of Sciences of the United States of America · 2025

Citation network

Articles citing this research paper

2 articles

Biohack Blueprint analyses that reference this study in their evidence base.

Editorial review

Reviewed by the Biohack Blueprint research team

Last verified

Dr. Khaled Mahmoud, MBBChCritical Care Medicine, Longevity Science & Editorial Direction Dr. Amr Yasser, PhDCardiometabolic, Musculoskeletal, Gut & Bioavailability Dr. Abdulla Mostafa, PhDCellular Senescence, Neurological, Mitochondrial & Brain-Ageing Biology