Life sciencesJun 27, 2024

Nicotine may cause aging in sperm stem cells by disturbing the daily balance of cell energy cycles through the SIRT6/Bmal1 pathway

Circadian Biology Weekly Brief ↗PubMed ↗DOI ↗

Updated Apr 2, 2026

Abstract

Nicotine exposure induces testis injury by triggering spermatogonia stem cell senescence.

Nicotine exposure upregulates senescence marker genes and components associated with senescence.
Mitochondrial hyper-fusion, increased oxidative stress, and DNA damage are observed following nicotine treatment.
Sirtuin 6 (SIRT6) expression is suppressed by nicotine, leading to accelerated senescence of spermatogonia stem cells.
Increased acetylation of Bmal1 occurs as a result of SIRT6 suppression, reducing Bmal1 protein expression.
Overexpression of Bmal1 can alleviate the mitochondrial hyper-fusion and senescence effects induced by nicotine.

Simplified

Infertility is intricately linked with alterations in circadian rhythms along with physiological decline and stem cell senescence. Yet, the direct involvement of circadian mechanisms in nicotine-induced injury to the testes, especially the senescence of spermatogonia stem cells (SSCs), is not well comprehended. This study revealed that nicotine exposure induced testis injury by triggering SSCs senescence along with the upregulation of senescence marker genes and senescence-associated secretory phenotype components. Moreover, nicotine treatment caused mitochondrial hyper-fusion, increased oxidative stress, and DNA damage. Exposure to nicotine was found to suppress the expression of sirtuin 6 (SIRT6), which accelerated the senescence of spermatogonia stem cells (SSCs). This acceleration led to increased acetylation of brain and muscle ARNT-like protein (Bmal1), consequently reducing the expression of Bmal1 protein. Conversely, the overexpression of Bmal1 alleviated mitochondrial hyper-fusion and senescence phenotypes induced by nicotine. Overall, this study unveiled a novel molecular mechanism behind nicotine-induced disorders in spermatogenesis and highlighted the SIRT6/Bmal1 regulatory pathway as a potential therapeutic target for combating nicotine-associated infertility.

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Nicotine may cause aging in sperm stem cells by disturbing the daily balance of cell energy cycles through the SIRT6/Bmal1 pathway

Abstract

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