Alterations of receptors and insulin-like growth factor binding proteins in senescent cells.

The knowledge about cellular senescence expands dynamically, providing more and more conclusive evidence of its triggers, mechanisms, and consequences. Senescence-associated secretory phenotype (SASP), one of the most important functional traits of senescent cells, is responsible for a large extent of their context-dependent activity. Both SASP's components and signaling pathways are well-defined. A literature review shows, however, that a relatively underinvestigated aspect of senescent cell autocrine and paracrine activity is the change in the production of proteins responsible for the reception and transmission of SASP signals, i.e., receptors and binding proteins. For this reason, we present in this article the current state of knowledge regarding senescence-associated changes in cellular receptors and insulin-like growth factor binding proteins. We also discuss the role of these alterations in senescence induction and maintenance, pro-cancerogenic effects of senescent cells, and aging-related structural and functional malfunctions.

Obesity in Hypertensive Patients Is Characterized by a Dawn Phenomenon in Systolic Blood Pressure Values and Variability.

One of the causes of hypertension is excess weight gain, which can also affect the course of this disease. Both the diagnosis and management of hypertension commonly use ambulatory blood pressure monitoring; the results of which correlate more strongly with cardiovascular diseases and cardiovascular death than office blood pressure monitoring. We evaluated blood pressure values and their variability from hour to hour to see if and when they differed between hypertensive patients with and without obesity. The study included 1345 patients who underwent 24 h ambulatory blood pressure monitoring and then were divided into groups according to body mass index and waist circumference. The obtained data were analyzed according to the subjects' wake-up time, and short-term blood pressure variability parameters were calculated as the mean of the absolute values of the differences between consecutive measurements. The systolic blood pressure in obese subjects was significantly higher between 1 and 5 h before waking than in normal-weighted individuals. In turn, the variability in systolic and diastolic blood pressure was higher with increasing body mass index. The difference in systolic blood pressure values and blood pressure variability was most prominent in the last 5 h of sleep in obese patients.

Mechanisms of carboplatin- and paclitaxel-dependent induction of premature senescence and pro-cancerogenic conversion of normal peritoneal mesothelium and fibroblasts.

Carboplatin (CPT) and paclitaxel (PCT) are the optimal non-surgical treatment of epithelial ovarian cancer (EOC). Although their growth-restricting influence on EOC cells is well known, their impact on normal peritoneal cells, including mesothelium (PMCs) and fibroblasts (PFBs), is poorly understood. Here, we investigated whether, and if so, by what mechanism, CPT and PCT induce senescence of omental PMCs and PFBs. In addition, we tested whether PMC and PFB exposure to the drugs promotes the development of a pro-cancerogenic phenotype. The results showed that CPT and PCT induce G2/M growth arrest-associated senescence of normal peritoneal cells and that the strongest induction occurs when the drugs act together. PMCs senesce telomere-independently with an elevated p16 level and via activation of AKT and STAT3. In PFBs, telomeres shorten along with an induction of p21 and p53, and their senescence proceeds via the activation of ERK1/2. Oxidative stress in CPT + PCT-treated PMCs and PFBs is extensive and contributes causatively to their premature senescence. Both PMCs and PFBs exposed to CPT + PCT fuel the proliferation, migration, and invasion of established (A2780, OVCAR-3, SKOV-3) and primary EOCs, and this activity is linked with an overproduction of multiple cytokines altering the cancer cell transcriptome and controlled by p38 MAPK, NF-κB, STAT3, Notch1, and JAK1. Collectively, our findings indicate that CPT and PCT lead to iatrogenic senescence of normal peritoneal cells, which paradoxically and opposing therapeutic needs alters their phenotype towards pro-cancerogenic. It cannot be excluded that these adverse outcomes of chemotherapy may contribute to EOC relapse in the case of incomplete tumor eradication and residual disease initiation. © 2023 The Pathological Society of Great Britain and Ireland.

Predictive role of monocyte count for significant coronary artery disease identification in patients with stable coronary artery disease.

BACKGROUND: The coronary artery disease (CAD) remains the leading cause of morbidity that is characterized by broad spectrum of symptoms. Up to 30% of performed angiographies reveal normal coronary arteries. The aim of the study was to find simple predictor for significant epicardial artery stenosis among patients with chronic coronary syndrome. METHODS: There were 187 patients (131 (709%) men and 56 (30%) women) in the median (Q1-Q3) age of 67 [58-72] presenting with stable CAD symptoms enrolled into the present retrospective analysis. The demographical, clinical and laboratory characteristics between patients with normal and significant coronary artery stenosis were compared. RESULTS: The multivariable analysis revealed coexistence of hypercholesterolemia as significant differentiation factor (odds ratio [OR]: 4.38, 95% confidence interval [CI]: 1.78-10.80, p = 0.001) for significant CAD and inverse relation to serum high density lipoprotein (OR: 0.19, 95% CI: 0.05-0.72, p = 0.015) and relation to creatinine concentration (OR: 1.03, 95% CI: 1.00-1.05, p = 0.012). Among whole peripheral blood count analysis, the significant relation was noticed to be hemoglobin concentration (OR: 1.09, 95% CI: 1.10-1.18, p = 0.022) and monocyte count (OR: 32.3, 95% CI: 1.09-653.6, p = 0.017). Receiver operator curve revealed (AUC: 0.641, p = 0.001) with the optimal cut-off value above 0.45 K/uL for monocyte, yelding sensitivity of 81.82% and specificity of 58.06%. CONCLUSIONS: The peripheral monocyte count above 0.45 k/uL may be considered as a predictor of significant coronary artery disease in symptomatic patients with chronic coronary syndrome.

Serum starvation-based method of ovarian cancer cell dormancy induction and termination in vitro.

Awakening and growth reinitiation by dormant cells may contribute to epithelial ovarian cancer (EOC) relapse. The links between these phenomena are loose because of the limited stock of compelling models of EOC dormancy. Here, we show a simple and convenient dormancy research protocol based on serum starvation. This study was conducted on established EOC cell lines A2780, OVCAR-3, and SKOV-3, as well as on primary EOC cells. Cell growth arrest and proliferation were monitored by assessing the Ki67 antigen, PKH26 fluorescence, and cell cycle distribution. In addition, cells were tested for ERK1/2/p38 MAPK activity ratio, apoptosis, and senescence. The study showed that 72-h serum starvation induces G0/G1 growth arrest of a significant fraction of cells, accompanied by reduced Ki67 and ERK1/2/p38 MAPK activity ratio, without signs of apoptosis or cellular senescence. Moreover, providing cells with 72 h of a medium enriched in 5% serum allows the culture to regain its proliferative potential. At the same time, we attempted to induce and terminate dormancy with Mitomycin C addition and withdrawal, which were unsuccessful. In conclusion, serum starvation is a convenient way to reliably induce dormancy in EOC cells, allowing them to be efficiently awakened for further mechanistic research in vitro.

Arterial Blood Pressure Features of Hypertensive Patients with Typical and Atypical 460 nm Skin Fluorescence Response to Transient Ischaemia.

Flow-mediated skin fluorescence (FMSF) at 460 nm is a non-invasive method for assessing dynamic changes in the reduced form of nicotinamide adenine dinucleotide (NADH) and microcirculation in forearm skin under varying conditions of tissue perfusion. Typically, fluorescence increases during ischaemia, but atypical cases show a temporary signal decrease instead of a constant increase. This study aimed to explore the clinical implications of atypical FMSF patterns in patients with newly diagnosed untreated hypertension. NADH fluorescence and pulse wave analysis were performed on 65 patients. Differences in peripheral and arterial pulse pressure profiles were examined based on FMSF curve courses. Patients with atypical curve courses had significantly (p < 0.05 or lower for all) higher heart rate, peripheral and central diastolic pressure, tension time index, central rate pressure product, shorter diastole duration, and reservoir pressure-time integral. Hypertensive patients with atypical FMSF signals had less advantageous blood pressure profiles. Although the underlying factors causing these symptoms are unknown, the atypical FMSF pattern may reflect increased sympathetic stimulation and vascular resistance. The visual assessment of the FMSF curve may have important clinical implications that deserve further investigation.

An integrative review of nonobvious puzzles of cellular and molecular cardiooncology.

Oncologic patients are subjected to four major treatment types: surgery, radiotherapy, chemotherapy, and immunotherapy. All nonsurgical forms of cancer management are known to potentially violate the structural and functional integrity of the cardiovascular system. The prevalence and severity of cardiotoxicity and vascular abnormalities led to the emergence of a clinical subdiscipline, called cardiooncology. This relatively new, but rapidly expanding area of knowledge, primarily focuses on clinical observations linking the adverse effects of cancer therapy with deteriorated quality of life of cancer survivors and their increased morbidity and mortality. Cellular and molecular determinants of these relations are far less understood, mainly because of several unsolved paths and contradicting findings in the literature. In this article, we provide a comprehensive view of the cellular and molecular etiology of cardiooncology. We pay particular attention to various intracellular processes that arise in cardiomyocytes, vascular endothelial cells, and smooth muscle cells treated in experimentally-controlled conditions in vitro and in vivo with ionizing radiation and drugs representing diverse modes of anti-cancer activity.

Correction: Pakula et al. Deciphering the Molecular Mechanism of Spontaneous Senescence in Primary Epithelial Ovarian Cancer Cells. Cancers 2020, 12, 296.

In the original publication [...].

Investigating the Ischaemic Phase of Skin NADH Fluorescence Dynamics in Recently Diagnosed Primary Hypertension: A Time Series Analysis.

The reduced form of nicotinamide adenine dinucleotide (NADH) is crucial in cellular metabolism. During hypoxia, NADH accumulation results from anaerobic cytoplasmic glycolysis and impaired mitochondrial function. This study aimed to compare the dynamic changes in the 460-nm forearm skin fluorescence, which reflects cellular NADH content, during transient ischaemia between healthy individuals and patients with newly diagnosed, untreated essential hypertension (HA). Sixteen healthy volunteers and sixty-five patients with HA underwent non-invasive measurement of forearm skin NADH content using the Flow Mediated Skin Fluorescence (FMSF) method at rest and during a 100-s transient ischaemia induced by inflation of the brachial cuff. The fluorescent signal was sampled at 25 Hz. All samples were normalised to the end of the ischaemic phase, which is the most stable phase of the whole recording. Slope values of 1 s linear regressions were determined for every 25-sample neighbouring set. The 1-s slopes in the early phase of skin ischaemia, indicating quicker hypoxia-induced NADH accumulation in skin, were significantly higher in patients with HA than in healthy individuals. These findings suggest that some protecting mechanisms postponing the early consequences of early cellular hypoxia and premature NADH accumulation during skin ischaemia are impaired in patients with untreated HA. Further studies are needed to investigate this phenomenon.

Target Blood Pressure Values in Ambulatory Blood Pressure Monitoring.

INTRODUCTION: 2018 ESC/ESH guidelines have recommended 24-h ambulatory blood pressure monitoring to assess hypotensive therapy in many circumstances. Recommended target blood pressure in office blood pressure measurements is between 120/70 and 130/80 mmHg. Such targets for 24-h ambulatory blood pressure monitoring lacks. AIM: We aimed to define target values of blood pressure in 24-h ambulatory blood pressure monitoring in hypertensive patients. METHODS: Office blood pressure measurements and 24-h ambulatory blood pressure monitoring data were collected from 1313 hypertensive patients and sorted following increasing systolic (SBP)/diastolic (DBP) blood pressure in office blood pressure measurements. The corresponding 24-h ambulatory blood pressure monitoring to office blood pressure measurements values were calculated. RESULTS: Values 130/80 mmHg in office blood pressure measurements correspond in 24-h ambulatory blood pressure monitoring: night-time SBP/DBP mean: 113.74/66.95 mmHg; daytime SBP/DBP mean: 135.02/81.78 mmHg and 24-h SBP/DBP mean: 130.24/78.73 mmHg. Values 120/70 mmHg in office blood pressure measurements correspond in 24-h ambulatory blood pressure monitoring: night-time SBP/DBP mean: 109.50/63.43 mmHg; daytime SBP/DBP mean: 131.01/78.47 mmHg and 24-h SBP/DBP mean: 126.36/75.31 mmHg. CONCLUSIONS: The proposed blood pressure target values in 24-h ambulatory blood pressure monitoring complement the therapeutic target indicated in the ESC/ESH recommendations and improves 24-h ambulatory blood pressure monitoring usefulness in clinical practice.

Potential of Volunteering in Formal and Informal Medical Education-A Theory-Driven Cross-Sectional Study with Example of the COVID-19 Pandemic.

Students' volunteering is an effective way to manage health crises, including pandemics. Due to the limited capacity of the healthcare system at the time of the COVID-19 outbreak, the engagement of students in volunteering services seemed invaluable. Based on different teaching-learning theories, in this survey study, we aimed to evaluate the potential of the volunteering service project launched by the Poznan University of Medical Sciences during the COVID-19 pandemic as a learning opportunity for undergraduate healthcare students. The results indicate the potential of involving students in volunteering activities for educational purposes, as well as other values, including attitudes and professional identity development, which could be difficult to realize using traditional teaching methods. However, stimulating students' reflectiveness seems necessary to reach its full educational effectiveness. Medical teachers should provide students with more opportunities for volunteering and service learning and consider making these a constant element of the curriculum beyond the COVID-19 pandemic.

Pro-cancerogenic effects of spontaneous and drug-induced senescence of ovarian cancer cells in vitro and in vivo: a comparative analysis.

BACKGROUND: Clinical outcomes of cancer cell senescence are still elusive. Here, we reveal and compare pro-cancerous activity of spontaneously and drug-inducible senescent ovarian cancer cells. Experiments were performed on tumors and tumor-derived primary epithelial ovarian cancer cells (pEOCs) that were obtained from chemotherapy-naïve patients and from patients who received carboplatin (CPT) and paclitaxel (PCT) before cytoreduction. RESULTS: The analysis of tumors showed that senescent cancer cells are present in patients from both groups, albeit most frequently and covering a greater area in tissues from chemotherapy-positive women. This in vivo senescence of pEOCs translated to an expression of senescence markers in early-passage cells in vitro. A conditioned medium from senescent pEOCs fueled the cancer progression, including adhesion of non-senescent pEOCs to normal peritoneal cells, and their increased proliferation, migration, invasion, and EMT. Senescent pEOCs' secretome promoted angiogenic activity of vascular endothelium, induced senescence of normal peritoneal cells, reprogrammed their secretome towards hypersecretion of cancer-promoting proteins, and stimulated motility of cancer cells subjected to a mesothelium- and fibroblast-derived medium. The most striking finding was, however, that spontaneously senescent pEOCs supported all the above pro-cancerous effects more efficiently than drug-inducible senescent cells, which was plausibly related to augmented release of several cancer spread mediators by these cells. The prevalence of spontaneously senescent pEOCs was most evident in experiments on mice when they were able, unlike the drug-inducible cells, to promote the development of drug-sensitive i.p. xenografts. CONCLUSIONS: Our study shows that spontaneous senescence of pEOCs should be treated as an independent pathogenetic factor of cancer progression.

The Effect of Antihypertensive Drugs on NADH in Newly Diagnosed Primary Hypertension.

Background: Some antihypertensive medications alter cellular energy production, presumably by modification of the mitochondrial function. In vivo studies of such effects are challenging in humans. We applied a noninvasive forearm skin measurement of the 460-nm fluorescence specific for the reduced form of nicotinamide adenine dinucleotide (NADH) to study the 6-week effects of four different antihypertensive medications on mitochondrial function using the Flow-Mediated Skin Fluorescence (FMSF). Methods: In a prospective open-label study, we compared the long-term effects of a 6-week treatment with either amlodipine (5 mg), perindopril (5 mg), nebivolol (5 mg), or metoprolol (50 mg) on the dynamic flow-mediated changes in the skin NADH content in 76 patients (29 women) with untreated primary arterial hypertension (HA). Patients underwent 24-hour ambulatory blood pressure monitoring. To study mitochondrial function, the FMSF was measured at rest, during 100-second ischemia and postischemic reperfusion. The control group consisted of 18 healthy people (7 women). Results: There were no significant differences in the FMSF parameters between the control and the study group before medication. After the 6-week treatment, all drugs similarly reduced blood pressure. Neither amlodipine, perindopril, nor nebivolol changed the flow-mediated 460-nm skin fluorescence significantly. However, metoprolol raised this fluorescence at rest, during ischemia and reperfusion (P at most <0.05), indicating an increase in the total NADH skin content. Conclusion: Amlodipine, perindopril, and nebivolol appear neutral for the skin NADH content during the 6-week antihypertensive treatment. Similar treatment with metoprolol increased skin NADH at rest, during ischemia and reperfusion, probably due to an effect on microcirculation and altered mitochondrial function. Explanation of the potential mechanisms behind metoprolol influence on the skin NADH metabolism requires further investigation.

Primary high-grade serous ovarian cancer cells are sensitive to senescence induced by carboplatin and paclitaxel in vitro.

BACKGROUND: Various types of normal and cancer cells undergo senescence in response to carboplatin and paclitaxel, which are considered the gold standard treatments in ovarian cancer management. Surprisingly, the effect of these drugs on ovarian cancer cell senescence remained unknown. METHODS: The experiments were conducted on primary high-grade serous ovarian cancer cells. Molecular markers of senescence were evaluated using cytochemistry and immunofluorescence. Cell cycle distribution was analyzed using flow cytometry. Expression of cyclins and signaling pathways was tested using western blot. Telomere length and telomerase activity were measured using qPCR, and the colocalization of telomeres with DNA damage foci using immuno-FISH. Oxidative stress-related parameters were quantified using appropriate fluorescence probes. Production of cancerogenic agents was analyzed using qPCR and ELISA. RESULTS: Carboplatin applied with paclitaxel induces senescence of ovarian cancer cells in vitro. This activity was reflected by permanent G2/M growth arrest, a high fraction of cells expressing senescence biomarkers (SA-ß-Gal and γ-H2A.X), upregulated expression of p16, p21, and p53 cell cycle inhibitors, and decreased expression of cyclin B1. Neither telomere length nor telomerase activity changed in the senescent cells, and the majority of DNA damage was localized outside telomeres. Moreover, drug-treated cancer cells exhibited increased production of STAT3 protein, overproduced superoxide and peroxides, and increased mitochondrial mass. They were also characterized by upregulated ANG1, CCL11, IL-6, PDGF-D, TIMP-3, TSP-1, and TGF-ß1 at the mRNA and/or protein level. CONCLUSIONS: Our findings imply that conventional chemotherapy may elicit senescence in ovarian cancer cells, which may translate to the development of a cancer-promoting phenotype, despite the inability of these cells to divide.

Visceral fat level correction of the left ventricular hypertrophy electrocardiographic criteria.

BACKGROUND: Left ventricular hypertrophy (LVH) is a well-known risk factor for cardiovascular events. Even though there are many electrocardiographic (ECG) criteria for LVH, they still provide poor performance, especially among obese patients. The aim of this study was to examine whether adding visceral fat to ECG LVH criteria improves accuracy in the diagnosis. METHODS: One thousand seven hundred twenty two patients were included in the study. All patients underwent a complete physical examination, office blood pressure measurement, analysis of body composition, 12-lead ECG, and M-mode two-dimensional echocardiography. Four standard ECG criteria for LVH were analyzed, including Cornell voltage criteria, Cornell duration criteria, Sokolow-Lyon voltage criteria, and Sokolow-Lyon product criteria. Adjustments of ECG LVH criteria were performed using visceral fat level (VFATL) and BMI. Transthoracic echocardiography was used as a reference method to compare the quality of ECG LVH criteria. RESULTS: Multivariate logistic regression models were created and revealed a significant increase of area under curve (AUC) after VFATL and BMI addition to ECG LVH criteria. Improvement of sensitivity at 90% specificity was observed in all created models. The odds ratio (OR) of the analyzed ECG criteria increased after adding VFATL and BMI to the models. Furthermore, ROC curves analysis exposed better characteristics in detecting LVH of VFATL-adjusted criteria than BMI-adjusted and unadjusted criteria. CONCLUSIONS: Adjusting ECG indexes to BMI or VFATL improves the sensitivity of LVH detection. VFATL-corrected indexes are more sufficiently than BMI-corrected. After advancements in indexes, both lean and morbidly obese individuals outcomes show a greater prevalence of correct LVH diagnosis.

Patient-Specific Variables Determine the Extent of Cellular Senescence Biomarkers in Ovarian Tumors In Vivo.

The mechanisms and clinical significance of the cellular senescence of tumor cells are a matter of ongoing debate. Recently, the triggers and molecular events underlying spontaneous, replicative senescence of primary epithelial ovarian cancer cells were characterized. In this study, we reanalyzed tumors obtained from ovarian cancer patients with respect to the expression of the senescence biomarkers SA-ß-Gal and γ-H2A.X and the proliferative antigen Ki67. The results showed that the tumors displayed strong heterogeneity with respect to the expression of analyzed markers. The expression of SA-ß-Gal and γ-H2A.X in the oldest patients (61-85 y.o.) was significantly higher than in the younger age groups. Conversely, the area of Ki67-positive cancer cells was greater in younger individuals. At the same time, there was a positive correlation between SA-ß-Gal expression and calendar age in FIGO III-IV and malignant ascites-positive patients. The γ-H2A.X positively correlated with age in the whole group, FIGO III-IV, and ascites-positive patients. Ki67 levels correlated negatively with the age of patients among those same groups. Collectively, our study indicated that organismal aging may determine the development of the senescence phenotype in ovarian tumors, particularly in patients with advanced disease and those accumulating malignant ascites.

Malignant Ascites Promote Adhesion of Ovarian Cancer Cells to Peritoneal Mesothelium and Fibroblasts.

Although malignant ascites (MAs) are known to contribute to various aspects of ovarian cancer progression, knowledge regarding their role in the adhesion of cancer cells to normal peritoneal cells is incomplete. Here, we compared the effect of MAs and benign ascites (BAs) on the adhesion of A2780 and OVCAR-3 cancer cells to omentum-derived peritoneal mesothelial cells (PMCs) and peritoneal fibroblasts (PFBs). The results showed that MAs stimulated the adhesion of A2780 and OVCAR-3 cells to PMCs and PFBs more efficiently than did BAs, and the strongest binding occurred when both cancer and normal cells were exposed to the fluid. Intervention studies showed that MAs-driven adhesion of A2780 cells to PMCs/PFBs depends on the presence of TGF-ß1 and HGF, whereas binding of OVCAR-3 cells was mediated by TGF-ß1, GRO-1, and IGF-1. Moreover, MAs upregulated α5ß1 integrin expression on PFBs but not on PMCs or cancer cells, vimentin expression in all cells tested, and ICAM-1 only in cancer cells. When integrin-linked kinase was neutralized in PMCs or PFBs, cancer cell adhesion to PMCs and PFBs decreased. Collectively, our report shows that MAs may contribute to the early stages of ovarian cancer metastasis by modulating the proadhesive interplay between normal and cancer cells.

Diverse functional responses to high glucose by primary and permanent hybrid endothelial cells in vitro.

Various types of human endothelial cells, including human umbilical vein endothelial cells (HUVECs) and the established hybrid EAhy926 cells, are used in experimental research. Here, we compared the biological properties of HUVECs and EAhy926 cells under normal (5 mM) and high glucose (30 mM; HG) conditions. The results showed that HG induced cellular senescence and a stronger DNA damage response in HUVECs than in EAhy926 cells. The magnitude of oxidative stress elicited in HUVECs by HG was also greater than that elicited in their established counterparts. Both endothelial cell types promoted the progression of breast (MCF7), ovarian (OVCAR-3), and lung (A549) cancer cells; however, the effects elicited by HG-treated HUVECs on adhesion (MCF7, OVCAR-3), proliferation (OVCAR-3), and migration (OVCAR-3) were more pronounced. Finally, HG stimulated the production of a higher number of proangiogenic agents in HUVECs than in EAhy926 cells. Collectively, our study shows that the functional properties of primary and established endothelial cells exposed to HG differ substantially, which seems to result from the higher sensitivity of the former to this stressor. The interchangeability of both types of endothelial cells in biomedical research should be considered with great care to avoid losing some biological effects due to the choice of cells with higher stress tolerance.

Nontraditional systems in aging research: an update.

Research on the evolutionary and mechanistic aspects of aging and longevity has a reductionist nature, as the majority of knowledge originates from experiments on a relatively small number of systems and species. Good examples are the studies on the cellular, molecular, and genetic attributes of aging (senescence) that are primarily based on a narrow group of somatic cells, especially fibroblasts. Research on aging and/or longevity at the organismal level is dominated, in turn, by experiments on Drosophila melanogaster, worms (Caenorhabditis elegans), yeast (Saccharomyces cerevisiae), and higher organisms such as mice and humans. Other systems of aging, though numerous, constitute the minority. In this review, we collected and discussed a plethora of up-to-date findings about studies of aging, longevity, and sometimes even immortality in several valuable but less frequently used systems, including bacteria (Caulobacter crescentus, Escherichia coli), invertebrates (Turritopsis dohrnii, Hydra sp., Arctica islandica), fishes (Nothobranchius sp., Greenland shark), reptiles (giant tortoise), mammals (blind mole rats, naked mole rats, bats, elephants, killer whale), and even 3D organoids, to prove that they offer biogerontologists as much as the more conventional tools. At the same time, the diversified knowledge gained owing to research on those species may help to reconsider aging from a broader perspective, which should translate into a better understanding of this tremendously complex and clearly system-specific phenomenon.