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Targeting metabolism in cellular senescence, a role for intervention.

Cellular senescence has gained much attention as a contributor to aging and susceptibility to disease. Senescent cells undergo a stable cell cycle arrest and produce pro-inflammatory cytokines. However, an additional feature of the senescence phenotype is an altered metabolic state. Despite maintaining a non-dividing state, senescent cells display a high metabolic rate. Metabolic changes characteristic of replicative senescence include altered mitochondrial function and perturbations in growth signaling pathways, such as the mTORC1-signaling pathway. Recent evidence has raised the possibility …

A transcriptome-based human universal senescence index (hUSI) robustly predicts cellular senescence under various conditions.

Despite the manifestation and contribution of cellular senescence to aging and various diseases, accurate identification of heterogeneous senescent cells remains challenging. Current senescence evaluation methods rely mainly on limited markers or homogeneous samples, which might fail to capture universal senescence features, limiting their generalizability. Here we developed the human universal senescence index (hUSI), an accurate and robust senescence evaluation method for diverse cells and samples. Based on features learned from the most comprehensive cellular senescence-associated transcrip…

Is microglial dystrophy a form of cellular senescence? An analysis of senescence markers in the aged human brain.

Aging can cause morphological transformation in human microglia indicative of cell senescence, termed microglial dystrophy. However, cellular senescence is characterized by additional changes, such as an irregular cell cycle arrest, and a variety of metabolic and molecular changes including a senescence-associated secretory phenotype, dysfunction of degradation mechanisms, and altered DNA damage response. Here, we tested whether dystrophic microglia display customary markers of cell senescence by performing double and triple staining in sections of the temporal lobe and brain stem from 14 huma…

Cellular senescence and inflammageing: from mechanisms to senotherapeutic interventions.

Cellular senescence is a context-dependent cellular state characterised by persistent cell-cycle arrest, epigenetic remodelling, metabolic reprogramming and acquisition of a senescence-associated secretory phenotype. Transient senescence contributes to embryogenesis, tissue repair and tumour suppression, whereas persistent senescent cell populations accumulate with advancing age across multiple tissues, in part owing to declining immune-mediated clearance and intrinsic resistance to apoptosis, thereby promoting chronic systemic inflammation, tissue fibrosis, stem-cell dysfunction and propagati…

Cellular senescence-from solid organs to vascularized composite allotransplants.

Vascularized composite allotransplantation (VCA) has emerged as a novel therapy approach to restore form and function in patients with severe tissue defects of the face, hand, and abdominal wall, among other anatomical regions. The composite allografts comprise different tissues such as skin, muscle, or bone. Clinical data demonstrate promising mid- and long-term outcomes following VCA surgery, but our understanding of the cellular interactions and molecular pathways in VCA surgery is oftentimes deduced from solid organ transplantation (SOT). In SOT, the concept of cellular senescence has grow…

Cellular senescence in migraine - a hypothesis-driven narrative review.

BACKGROUND: Migraine may signal early signs of aging-related processes, such as reduced autophagy, increased reactive oxygen and nitrogen species (RONS), and low-grade inflammation in people prone to migraine, without necessarily indicating systemic aging. While migraine is not an age-related condition, brain aging might be accelerated by cellular senescence in neurons and glia, contributing to cognitive decline in migraine patients. Although neurons are postmitotic cells, they can undergo postmitotic cellular senescence, which may contribute to the chronicity of migraine. MAIN BODY: Oxidative…

SERPINE1 (PAI-1) Regulation in Mechanotransduction-Associated Cellular Senescence.

Cellular senescence is a complex biological process characterized by irreversible cell-cycle arrest and acquisition of the senescence-associated secretory phenotype (SASP). Beyond biochemical stress, increasing evidence indicates that mechanical cues from the extracellular microenvironment contribute to the regulation of senescence; however, the molecular mechanisms linking mechanotransduction to senescent phenotypes remain incompletely understood. SERPINE1 (plasminogen activator inhibitor-1, PAI-1) has emerged as a key mechanosensitive effector induced downstream of mechanotransduction signal…

Cellular senescence and senolytic therapy in traumatic brain injury.

Traumatic brain injury (TBI) is a major cause of death and long-term disability in the United States. The initial primary injury in TBI is followed by a secondary injury cascade of molecular events, which can persist for years, and contributes to neuroinflammation, neurodegeneration, and long-term functional deficits after TBI. In this review, we will discuss evidence that cellular senescence in TBI, where damaged cells enter a state of permanent cell-cycle arrest and release pro-inflammatory factors, is a component of the secondary injury cascade, which contributes to both chronic neuroinflam…

Liver Regeneration: Polyploidy and Cellular Senescence as Potential Regulators.

The liver is a highly versatile and resilient organ that is crucial for metabolism, detoxification, digestion, and immune regulation. Its remarkable regenerative capacity is driven primarily by two key cellular processes: hepatocyte polyploidy and cellular senescence. This review explores the complex roles of polyploidy, in which hepatocytes possess multiple chromosome sets, and senescence, characterized by irreversible cell cycle arrest, in maintaining liver homeostasis and facilitating regeneration. Polyploid hepatocytes increase genetic and metabolic diversity, enabling the liver to withsta…

Cellular Senescence in Kidney Diseases: From Bench to Clinic.

Kidney diseases, including acute kidney injury (AKI), chronic kidney disease (CKD), and renal cell carcinoma (RCC), are global public health problems with high morbidity and mortality. Cellular senescence, which represents a state of irreversible cell-cycle arrest accompanied by functional deterioration, is closely associated with AKI, CKD, and RCC. Senescent cells, including tubular epithelial cells, endothelial cells, fibroblasts, podocytes, macrophages, and vascular smooth muscle cells, have been detected in the kidneys of patients, animals, and cells with AKI, CKD, and RCC. However, the ro…

Сенсорность клеток в глиальных клетках: последствия для множественного склероза.

Старение является наиболее распространенным фактором риска для развития заболевания множественным склерозом (MS). Клеточная сенсация, необратимое состояние остановки клеточного цикла, является основным фактором старения и, как было установлено, накапливается преждевременно в нейродегенеративных заболеваниях, включая болезнь Альцгеймера и Паркинсона. В последнее время внимание привлекает клеточная сенсация в центральной нервной системе пациентов MS, при этом ряд исследований свидетельствуют о том, что демиелинация вызывает клеточную сенесценцию с общими признаками p16INK4A и p21 выражения, окис

Совпадение в аннотации оригинала
Aging is the most common risk factor for Multiple Sclerosis (MS) disease progression. Cellular senescence, the irreversible state of cell cycle arrest, is the main driver of aging and has been found to accumulate prematurely in neurodegenerative diseases, including Alzheimer's and Parkinson's disease. Cellular senescence in the central nervous system of MS p…

Cellular senescence in acute kidney injury: Target and opportunity.

Acute kidney injury (AKI) is a common clinical disease with a high incidence and mortality rate. It typically arises from hemodynamic alterations, sepsis, contrast agents, and toxic drugs, instigating a series of events that culminate in tissue and renal damage. This sequence of processes often leads to acute renal impairment, prompting the initiation of a repair response. Cellular senescence is an irreversible arrest of the cell cycle. Studies have shown that renal cellular senescence is closely associated with AKI through several mechanisms, including the promotion of oxidative stress and in…

Cellular senescence in liver diseases: From mechanisms to therapies.

Cellular senescence is an irreversible state of cell cycle arrest, characterized by a gradual decline in cell proliferation, differentiation, and biological functions. Cellular senescence is double-edged for that it can provoke organ repair and regeneration in physiological conditions but contribute to organ and tissue dysfunction and prime multiple chronic diseases in pathological conditions. The liver has a strong regenerative capacity, where cellular senescence and regeneration are closely involved. Herein, this review firstly introduces the morphological manifestations of senescent cells, …

Cellular Stress and Senescence Induction during Trypanosoma cruzi Infection.

Chagas disease (CD) is a neglected tropical disease caused by Trypanosoma cruzi infection that, despite being discovered over a century ago, remains a public health problem, mainly in developing countries. Since T. cruzi can infect a wide range of mammalian host cells, parasite-host interactions may be critical to infection outcome. The intense immune stimulation that helps the control of the parasite's replication and dissemination may also be linked with the pathogenesis and symptomatology worsening. Here, we discuss the findings that support the notion that excessive immune system stimulati

Helicobacter pylori-positive chronic atrophic gastritis and cellular senescence.

BACKGROUND: Chronic atrophic gastritis (CAG) is a pathological stage in the Correa's cascade, whereby Helicobacter pylori (H. pylori) infection is the primary cause. Cellular senescence is an inducing factor for cancer occurrence and cellular senescence is an obvious phenomenon in gastric mucosal tissues of H. pylori-positive CAG patients. METHODS: In this review, we collated the information on cellular senescence and H. pylori-positive CAG. RESULTS: At present, only a few studies have observed the effect of cellular senescence on precancerous lesions. In combination with the latest research…

Extracellular matrix and cellular senescence in venous leg ulcers.

High prevalence of non-healing chronic wounds contributes to a huge healthcare burden across the world. Early treatment interventions for no … e of collagen imaging in cutaneous wound assessment for a faster and non-invasive method to predict cellular senescence and determining wound trajectory of healing.

Cellular senescence impairs the reversibility of pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) in congenital cardiac shunts can be reversed by hemodynamic unloading (HU) through shunt closure. However, this reversibility potential is lost beyond a certain point in time. The reason why PAH becomes irreversible is unknown. In this study, we used MCT+shunt-induced PAH in rats to identify a dichotomous reversibility response to HU, similar to the human situation. We compared vascular profiles of reversible and irreversible PAH using RNA sequencing. Cumulatively, we report that loss of reversibility is associated with a switch from a proliferative to a s

Converging Paths of Pulmonary Arterial Hypertension and Cellular Senescence.

Cellular senescence is recognized as a crucial contributor to the pathobiology of various degenerative and cardiovascular diseases, such as idiopathic pulmonary fibrosis and atherosclerosis. We describe the potential link between cellular senescence and the degenerative character of neointimal pulmonary vascular disease in pulmonary arterial hypertension (PAH). Senescence markers have been described in remodeled pulmonary arteries, and PAH and senescence share common triggers and pathogenic pathways, such as transforming growth factor-β/bone morphogenetic protein and TNF-α. In addition, interv…

Paracrine cellular senescence exacerbates biliary injury and impairs regeneration.

Cellular senescence is a mechanism that provides an irreversible barrier to cell cycle progression to prevent undesired proliferation. However, under pathological circumstances, senescence can adversely affect organ function, viability and regeneration. We have developed a mouse model of biliary senescence, based on the conditional deletion of Mdm2 in bile ducts under the control of the Krt19 promoter, that exhibits features of biliary disease. Here we report that senescent cholangiocytes induce profound alterations in the cellular and signalling microenvironment, with recruitment of myofibrob…

Understanding Diabetic Induction of Cellular Senescence: A Concise Review.

OBJECTIVE: This study examines the healing dynamics of in vivo porcine muscle tissue wounds hemostatically treated with a saline-coupled bipolar tissue sealer (SCBS) compared with traditional electrosurgical (ES) coagulation. MATERIALS AND METHODS: Six cutaneous incisions were created on the dorsum of 28 adult male Yorkshire swine. The underlying muscle tissue was incised with a cold scalpel then treated with either SCBS (at 170 W) or traditional ES (at Coag 45 W). Time to hemostasis was recorded. Animals were humanely euthanized at day 2 and weeks 2, 3, or 8; treated tissue was harvested for