A systematic evaluation of SIRT6 as transcriptomic biomarker of aging
- 1Central University, Skolkovo Institute of Science and Technology
Abstract
SIRT6 is a NAD+-dependent sirtuin that plays central roles in chromatin regulation, DNA repair, telomere maintenance, metabolic homeostasis, and inflammatory control. Although SIRT6 have long been implicated in aging because of its association with several hallmarks of aging, the available evidence remains largely context-dependent and mechanistic, limiting the interpretation of SIRT6 as a robust and evolutionarily conserved biomarker of aging. To comprehensively investigate the role of SIRT6 as an aging biomarker, we established SIRT6.db, a multi-species transcriptomic resource that integrates SIRT6-targeted perturbation experiments across diverse biological systems and organisms form all available SIRT6-related publications collected via a large-scale textual analysis of the SIRT6 literature using topic modeling. Based on this database, we identified both species-specific and evolutionarily conserved transcriptional and functional signatures associated with SIRT6 perturbation and established their relevance to hallmarks of aging. We showed that SIRT6 expression is generally stable during normal aging, but becomes dysregulated in Alzheimer's disease in cell type and stage-specific manner, highlighting the context dependence of its potential as a transcriptomic biomarker of aging.
Related
- An alignment-last approach enables rapid transcriptomic biomarker discovery in large cohorts
- Integrated transcriptomic analysis identifies Paternally Expressed Gene 10 as a novel candidate biomarker associated with aggressive features in liposarcoma
- Stress-recovery dynamics reveal a separatrix in transcriptomic landscapes across organs and aging
- Single-cell transcriptomic and epigenomic analysis reveals X-linked sex differences in aging mouse hypothalamus
- Age-specific genomic and transcriptomic variation reveals limited evidence for cis-regulatory interactions modulating aging in Saccharomyces cerevisiae
BibTeX
@misc{kashuk2026systematic,
title = {{A systematic evaluation of SIRT6 as transcriptomic biomarker of aging}},
author = {E. Kashuk and A. Tarakanova and A. Malygina and N. Kuzovkina and A. Ponomareva and D. Toiber and E. Khrameeva and D. Smirnov},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.03.749075},
url = {https://www.biorxiv.org/content/10.64898/2026.09.03.749075v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - A systematic evaluation of SIRT6 as transcriptomic biomarker of aging
AU - E. Kashuk
AU - A. Tarakanova
AU - A. Malygina
AU - N. Kuzovkina
AU - A. Ponomareva
AU - D. Toiber
AU - E. Khrameeva
AU - D. Smirnov
PY - 2026
DA - 2026/09/03
PB - bioRxiv
DO - 10.64898/2026.09.03.749075
UR - https://www.biorxiv.org/content/10.64898/2026.09.03.749075v1
AB - SIRT6 is a NAD+-dependent sirtuin that plays central roles in chromatin regulation, DNA repair, telomere maintenance, metabolic homeostasis, and inflammatory control. Although SIRT6 have long been implicated in aging because of its association with several hallmarks of aging, the available evidence remains largely context-dependent and mechanistic, limiting the interpretation of SIRT6 as a robust and evolutionarily conserved biomarker of aging. To comprehensively investigate the role of SIRT6 as an aging biomarker, we established SIRT6.db, a multi-species transcriptomic resource that integrates SIRT6-targeted perturbation experiments across diverse biological systems and organisms form all available SIRT6-related publications collected via a large-scale textual analysis of the SIRT6 literature using topic modeling. Based on this database, we identified both species-specific and evolutionarily conserved transcriptional and functional signatures associated with SIRT6 perturbation and established their relevance to hallmarks of aging. We showed that SIRT6 expression is generally stable during normal aging, but becomes dysregulated in Alzheimer's disease in cell type and stage-specific manner, highlighting the context dependence of its potential as a transcriptomic biomarker of aging.
ER -