Journal September 27, 2026 4 min read

What does the research say about cellular senescence?

Cellular senescence is a stress response marked by irreversible cell-cycle arrest and a pro-inflammatory secretome. Research across organ systems has identified molecular regulators, from LSD1-ATM signaling to SASP remod

peptides-pro Editorial

Cellular senescence is a stress response triggered by age-associated insults, characterized by irreversible cell-cycle arrest and a pro-inflammatory senescence-associated secretory phenotype (SASP) [1][4]. It is a hallmark of aging and contributes to tissue dysfunction across organs [1][2].

The work centres on the DNA damage response pathway, particularly ATM signaling, and its regulation by lysine-specific demethylase 1 (LSD1) [1].

Research Studies

LSD1 and DNA damage-mediated senescence in aged organs

LSD1 was upregulated in aged organs and senescent cells. In response to natural aging or ionizing radiation-induced DNA damage, LSD1 interacted with and demethylated ATM at lysine 3,016, sustaining ATM phosphorylation, amplifying DNA damage signaling, and promoting senescence and organ aging [1].

Bone aging as multiscale degeneration

Bone aging involves declines in bone mass, microstructure, and biomechanical properties, spanning molecular, cellular, tissue, and system levels [2]. This review synthesizes the landscape of bone aging and highlights the need for integrated intervention strategies [2].

Ergothioneine and OCTN1-dependent tissue distribution

Ergothioneine (EGT) is a diet-derived sulfur-containing histidine derivative with antioxidant, anti-inflammatory, and cytoprotective properties. Its absorption, tissue distribution, and long-term retention are mainly mediated by the organic cation transporter OCTN1, which may explain its accumulation in metabolically active and stress-prone tissues [3]. Experimental and clinical evidence links EGT to neurodegenerative, cardiovascular, metabolic, inflammatory, and age-related disorders, though its therapeutic value requires confirmation in larger and longer-term clinical studies [3].

SASP-mediated remodeling of the tumor microenvironment

SASP comprises inflammatory cytokines, chemokines, growth factors, and matrix-remodeling enzymes that regulate the tumor microenvironment (TME). Cellular senescence influences cancer progression through irreversible cell-cycle arrest, immune surveillance, and paracrine signaling mediated by SASP [4]. Emerging strategies target senescent cells and SASP signaling [4].

PQQ and mitochondrial rejuvenation in skin

Mitochondrial dysfunction is a central contributor to intrinsic skin aging, photoaging, cellular senescence, impaired extracellular-matrix homeostasis, dysregulated pigmentation, and delayed recovery after energy-based or minimally invasive procedures. Pyrroloquinoline quinone (PQQ) is a redox-active ortho-quinone that can participate in repeated redox cycling, protect mitochondrial function, and activate signaling associated with mitochondrial biogenesis [5]. This narrative review evaluates the mechanistic basis and available dermatologic evidence, noting major uncertainties [5].

Oxidative stress, SIRT1, and the gut microbiota in cognitive loss

Cardiovascular disease and cognitive loss have a neurocardiac basis. Poor vascular perfusion can impair cognitive function in Alzheimer's disease and multiple sclerosis. Current treatments often fail to fully address the shared underlying cellular mechanisms, and a treatment gap exists [6]. The review discusses oxidative stress, aging, metabolism, SIRT1, and the gut microbiota in this context [6].

ETS1/DRP1 axis in intervertebral disc degeneration

Intervertebral disc degeneration (IVDD) is characterized by nucleus pulposus cell (NPC) senescence, extracellular matrix metabolic dysfunction, and chronic inflammation. Excessive mitochondrial fission contributes to IVDD. ETS1 was upregulated in severe human IVDD and correlated with disc degeneration severity and NPC senescence. Inflammatory cytokines induced ETS1 upregulation, which directly bound to the dynamin 1-like (DNM1L, encoding DRP1) promoter and attenuated IVDD by suppressing excessive mitochondrial fission [7].

Nebivolol and hypertension-induced endothelial cell senescence

Serum from patients with hypertension causes endothelial cell damage, leading to senescence and dysfunctional phenotype. In a study of 71 patients with newly diagnosed hypertension randomized to amlodipine, nebivolol, or perindopril, serum samples collected before and 6 weeks after treatment were applied to endothelial cells in vitro to assess angiogenic activity, cellular senescence, mitochondrial metabolism, and oxidative stress. Nebivolol treatment improved hypertension-induced endothelial cell dysfunction by reducing TGF-β1-dependent senescence and normalizing mitochondrial indices [8].

Senescence in ALS, liver aging, atrial fibrillation, and immune clearance

Cellular senescence is an early feature and therapeutic target in amyotrophic lateral sclerosis TDP-43^Q331K mice [9]. Hepassocin prevents age-related liver senescence and facilitates liver regeneration by activating AMPK [10]. Radiation-induced atrial fibrillation is driven by cellular senescence via the GATA4-NF-κB pathway and rescued by D/Q senolytic therapy [11]. Blocking PD-L2 prevents senescent cell accumulation and age-related dysfunction [12].

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