Mitochondrial dysfunction and cell senescence: cause or consequence?

The mitochondrial theory of aging remains to date one of the most popular theories of aging. One major model of aging is replicative senescence, where the irreversible loss of division potential of somatic cells occurs after a more or less constant number of cell divisions. Few data are available concerning the role of mitochondria in this model. Here, we review evidence supporting the involvement of mitochondria in replicative senescence and a possible link to telomere biology. Moreover, we suggest that this process might be more complex than originally formulated, because variations in nuclear gene expression involved in mitochondrion nucleus cross-talk are observed in both senescence and immortalization.     

Chondrocyte apoptosis: a cause or consequence of osteoarthritis?

Osteoarthritis (OA) is a degenerative joint disease characterized by articular cartilage degradation and changes in the subchondral bone. Over the last two decades, there has been increasing evidence showing association between cartilage degradation and chondrocyte death, and different types of cell death in cartilage have been reported, including apoptosis and chondroptosis as well as necrosis, but which of these types of cell death predominate in OA is debatable. There are also some methodological difficulties in detecting the specific form of cell death in articular cartilage. Current 'gold standard' for detecting chondrocyte death is electron microscopy which suggests that the morphological changes of chondrocytes in OA cartilage are attributed to apoptosis and/or chondroptosis. However, the current literature appears to suggest that classic apoptosis plays an important role in OA; but whether chondrocyte apoptosis is a cause or a result of cartilage degeneration in OA is hotly contested. Studies of suitable animal models, especially longitudinal studies, are needed to address the cause-and-effect relationship.     

C-reactive protein and atrial fibrillation. Is inflammation a consequence or a cause of atrial fibrillation?

To clarify whether inflammation is a cause or consequence of atrial fibrillation (AF), we measured high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-alpha) before and after pharmacological cardioversion in 15 patients with paroxysmal AF. Levels of hs-CRP, IL-6, and TNF-alpha after cardioversion were significantly higher than those in controls (P < 0.05). Furthermore, the levels of these indices did not differ significantly even at 24 hours and 2 weeks after cardioversion. These results suggest that inflammation is a causative agent of paroxymal AF.     

Is rest or exercise hypertension a cause of a false-positive exercise test?

STUDY OBJECTIVES: To determine if a history of hypertension or an exaggerated rise in exercise systolic BP is associated with a false-positive exercise ECG. DESIGN, SETTING, AND PATIENTS: Retrospective analysis of the associations between exercise-induced ST-segment depression and a history of hypertension, exercise systolic BP, and several other clinical and exercise test variables. Among 20,097 patients referred for exercise tomographic thallium imaging in a nuclear cardiology laboratory at a tertiary care center, 1,873 patients met inclusion criteria for this study, which included no history of myocardial infarction or coronary artery revascularization, a normal resting ECG, and normal exercise thallium images. RESULTS: False-positive ST-segment depression occurred in 20% of the population. A history of hypertension was actually associated with a lower likelihood of ST-segment depression (odds ratio, 0.70; 95% confidence interval [CI], 0.55 to 0.89; p = 0. 004). A higher peak exercise systolic BP was associated with a higher likelihood of ST-segment depression (odds ratio, 1.08 for each 10-mm Hg increase in systolic BP; 95% CI, 1.03 to 1.14; p < 0. 001). However, the association between peak exercise systolic BP and ST-segment depression was so weak that this measurement could not be predictive in the individual patient (R(2) = 0.2%). For every 20-mm Hg increase in peak exercise systolic BP, the percentage of patients with ST-segment depression increased by only 3%. CONCLUSIONS: In patients with normal resting ECGs, we conclude the following: (1) a history of hypertension is not a cause of a false-positive exercise test, and (2) higher exercise systolic BP is a significant but weak predictor of ST-segment depression.     

Elevated plasma homocysteine: cause or consequence of myocardial infarction?

OBJECTIVES: To determine whether a first myocardial infarction leads to increased plasma homocysteine concentrations and whether the association between homocysteine and myocardial infarction was greater at follow-up compared with baseline. DESIGN: A population-based, prospective, nested case-referent study. SETTING: Screening took place at the nearest health survey centre in northern Sweden. SUBJECTS: Of more than 36,000 persons screened, 78 developed a first myocardial infarction (average 18 months after sampling). Fifty of these had participated in a follow-up health survey (average 8(1/2) years between surveys) and were sex- and age-matched with 56 referents. MAIN OUTCOME MEASURES: Comparison of plasma homocysteine levels in case and referent subjects before and after development of a first myocardial infarction. RESULTS: No statistically significant difference was found between cases and referents regarding homocysteine at baseline or follow-up. Plasma homocysteine and plasma creatinine increased significantly, and plasma albumin decreased significantly over time. Conditional univariate logistic regression indicated that high homocysteine at follow-up but not baseline was associated with first myocardial infarction (OR 2.49; 95% CI: 1.03-6.02), but the relation disappeared in multivariate analyses including plasma creatinine and plasma albumin. High plasma creatinine remained associated with first myocardial infarction at both baseline (OR 2.94; 95% CI: 1.05-8.21) and follow-up (OR 3.38; 95% CI: 1.21-9.48). CONCLUSION: In this study, first myocardial infarction did not cause increased plasma homocysteine concentration.     

Is increased uric acid a risk factor or a defensive response? The Campania Salute Network

Background and aims

Circulating uric acid (UA) is positively associated with body mass index (BMI), blood glucose, blood pressure (BP), markers of inflammation, and altered lipid profile. UA has also anti-oxidative properties which might be beneficial for cardiovascular (CV) system. It is still debated whether or not UA is independently associated with increased CV morbidity and/or mortality.

Mutations of mitochondrial DNA – cause or consequence of the ageing process?

Ageing is a stochastic process which leads to a gradual decline in cellular, tissue and even organ function, especially in energy dependent postmitotic tissues like skeletal muscle, brain and heart. The mitochondrial theory of ageing is based on the assumption that reactive oxygen species (ROS) and free radicals generated in the immediate vicinity of the electron transport chain during the lifespan of an organism damage proteins, lipids and mitochondrial DNA (mtDNA). Whereas it was generally believed that mitochondria are among the important players regarding the ageing process, two recent important approaches shed new light on the complex interactions. It has been shown by single cell experiments and computer simulation models that mitochondrial mutations are generated stochastically in childhood or early adolescence and accumulate clonally in a cell or muscle fibre, leading to a local age related impairment of cellular energy supply. Other important observations come from mitochondrial mutator mice, harbouring mitochondrial mutations due to a deficient repair enzyme (POLG). These mice reveal a premature senescence but do not exhibit a vicious cycle of increased oxidative damage or ROS production as has been postulated by the mitochondrial theory of ageing. At the moment it is hard to decide, if mitochondrial mutations are the cause or consequence of human ageing, but it is suggested that mitochondrial point mutations are just the consequence, while deletions seem to play a causal role.     

Malabsorption in psoriatic patients: cause or consequence?

OBJECTIVE: The etiopathogenesis of psoriasis is still unclear. Associations between gut and skin diseases are well known, since psoriatic patients show a high prevalence of coeliac disease. Small-bowel abnormalities can cause clinical or, more frequently, laboratory alterations that give rise to malabsorption. The aim of the study was to evaluate the prevalence of malabsorption in psoriatic patients. MATERIAL AND METHODS: Fifty-five (29 M, 26 F, mean age 51+/-8 years) psoriatic patients in the Dermatology Centre of our hospital and 65 healthy controls (36 M, 29 F, mean age 47+/-9 years) were screened for malabsorption using a D-xylose test. Psoriatic subjects who resulted positive were further investigated in order to reach a better characterization of the malabsorption using serum antigliadin, anti-endomysium and anti-transglutaminase antibodies, H2 lactulose breath test, the parasitological faecal test and colonoscopy with retrograde ileoscopy. RESULTS: Altered D-xylose absorption was found in 60% (33/55) of psoriatic patients and in 3% (2/65) of controls. Of the former, 6% had coeliac disease, 21% had bacterial overgrowth, 3% had parasitic infections and 1 patient presented eosinophilic gastroenteritis. CONCLUSIONS: Malabsorption was more prevalent among psoriatic patients than among controls. Coeliac disease, bacterial overgrowth, parasitic infestations and eosinophilic gastroenteritis could be possible causes of malabsorption in these patients. Further studies are needed to clarify the pathogenesis and possible causative associations between gut and skin diseases.     

Angiogenesis and chronic inflammation: cause or consequence?

Evidence has been gathered regarding the association between angiogenesis and inflammation in pathological situations. These two phenomena have long been coupled together in many chronic inflammatory disorders with distinct etiopathogenic origin, including psoriasis, rheumatoid arthritis, Crohn’s disease, diabetes, and cancer. Lately, this concept has further been substantiated by the finding that several previously established non-inflammatory disorders, such as osteoarthritis and obesity, display both inflammation and angiogenesis in an exacerbated manner. In addition, the interplay between inflammatory cells, endothelial cells and fibroblasts in chronic inflammation sites, together with the fact that inflammation and angiogenesis can actually be triggered by the same molecular events, further strengthen this association. Therefore, elucidating the underlying cellular and molecular mechanisms that gather together the two processes is mandatory in order to understand their synergistic effect, and to develop new therapeutic approaches for the management of these disorders that cause a great deal of discomfort, disability, and in some cases death.