Ageing is a multifactorial physiological manifestation that occurs inexorably and gradually in all forms of life. This process is linked to the decay of homeostasis due to the progressive decrease in the reparative and regenerative capacity of tissues and organs, with reduced physiological reserve in response to stress. Ageing is closely related to oxidative damage and involves immunosenescence and tissue impairment or metabolic imbalances that trigger inflammation and inflammasome formation. One of the main ageing-related alterations is the dysregulation of the immune response, which results in chronic low-level, systemic inflammation, termed “inflammaging”. Genetic and epigenetic changes, as well as environmental factors, promote and/or modulate the mechanisms of ageing at the molecular, cellular, organ, and system levels. Most of these mechanisms are characterized by time-dependent patterns of variation driven by the biological clock. In this review, we describe the involvement of ageing-related processes with inflammation in relation to the functioning of the biological clock and the mechanisms operating this intricate interaction.

Melatonin (MT) and sirtuins (SIRT) are geroprotective molecules that hold back the aging process and the development of age-related diseases, including cardiovascular pathologies. Buccal epithelium (BE) sampling is a non-invasive procedure, yielding highly informative material for evaluating the expression of genes and proteins as well as the synthesis of molecules. Among these, MT and SIRTs are valuable markers of the aging process and age-related pathologies. The purpose of this study was to examine age-related expression patterns of these signaling molecules, in particular MT, SIRT1, SIRT3, and SIRT6 in BE of subjects of different ages with and without arterial hypertension (AH). We used real-time polymerase chain reaction (RT-PCR) and immunofluorescence analysis by confocal microscopy. We found that MT immunofluorescence intensity in BE decreases with aging, more evidently in AH patients. SIRT3 and SIRT6 genes expression and immunofluorescence intensity in BE was decreased in aging controls. In AH patients, SIRT1, SIRT3, and SIRT6 gene expression and immunofluorescence intensity in BE was decreased in relation to age and in comparison with age-matched controls. In conclusion, the evaluation of MT and sirtuins in BE could provide a non-invasive method for appraising the aging process, also when accompanied by AH.

Cardiac amyloidosis (CA), caused by the deposition of insoluble amyloid fibrils, impairs different cardiac structures, altering not only left ventricle (LV) systo-diastolic function but also atrial function and the conduction system. The consequences of the involvement of the cardiac electrical system deserve more attention, as well as the study of the underlying molecular mechanisms. This is an issue of considerable interest, given the conflicting data on the effectiveness of conventional antiarrhythmic strategies. Therefore, this review aims at summarizing the arrhythmic burden related to CA and the available evidence on antiarrhythmic treatment in this population.

Orthopaedic manifestations of wild-type transthyretin amyloidosis are frequent and characteristic, including idiopathic bilateral carpal tunnel syndrome, idiopathic lumbar canal stenosis, atraumatic rupture of the brachial biceps tendon, and, more rarely, finger disease and rotator cuff. These manifestations often coexisting in the same patient, frequently male and aged, steadily precede cardiac involvement inducing a rapidly progressive heart failure with preserved ejection fraction. Although transthyretin cardiac amyloidosis remains a cardiac relevant disease, these extracardiac localisation may increase diagnostic suspicion and allow for early diagnosis assuming the role of useful diagnostic red flags, especially in light of new therapeutic opportunities that can slow or stop the progression of the disease. For the cardiologist, the recognition of these extracardiac red flags is of considerable importance to reinforce an otherwise less emerging diagnostic suspicion. For orthopedists and rheumatologists, the presence in an old patient with or without clinical manifestations of cardiovascular disease, of an unexpected and inexplicable constellation of musculoskeletal symptoms, can represent a fundamental moment for an early diagnosis and treatment is improving a patient’s outcome.

Acute Respiratory Distress Syndrome (ARDS) caused by COVID-19 is substantially different from ARDS caused by other diseases and its treatment is dissimilar and challenging. As many studies showed conflicting results regarding the use of Non-invasive ventilation in COVID-19-associated ARDS, no unquestionable indications by operational guidelines were reported. The aim of this study was to estimate the use and success rate of Helmet (h) Continuous Positive Airway Pressure (CPAP) in COVID-19-associated ARDS in medical regular wards patients and describe the predictive risk factors for its use and failure. In our monocentric retrospective observational study, we included patients admitted for COVID-19 in medical regular wards. hCPAP was delivered when supplemental conventional or high-flow nasal oxygen failed to achieve respiratory targets. The primary outcomes were hCPAP use and failure rate (including the need to use Bilevel (BL) PAP or oro-tracheal intubation (OTI) and death during ventilation). The secondary outcome was the rate of in-hospital death and OTI. We computed a score derived from the factors independently associated with hCPAP failure. Out of 701 patients admitted with COVID-19 symptoms, 295 were diagnosed with ARDS caused by COVID-19 and treated with hCPAP. Factors associated with the need for hCPAP use were the PaO₂/FiO₂ ratio < 270, IL-6 serum levels over 46 pg/mL, AST > 33 U/L, and LDH > 570 U/L; age > 78 years and neuropsychiatric conditions were associated with lower use of hCPAP. Failure of hCPAP occurred in 125 patients and was associated with male sex, polypharmacotherapy (at least three medications), platelet count < 180 × 10⁹/L, and PaO₂/FiO₂ ratio < 240. The computed hCPAP-f Score, ranging from 0 to 11.5 points, had an AUC of 0.74 in predicting hCPAP failure (significantly superior to Call Score), and 0.73 for the secondary outcome (non-inferior to IL-6 serum levels). In conclusion, hCPAP was widely used in patients with COVID-19 symptoms admitted to medical regular wards and developing ARDS, with a low OTI rate. A score computed combining male sex, multi-pharmacotherapy, low platelet count, and low PaO₂/FiO₂ was able to predict hCPAP failure in hospitalized patients with ARDS caused by COVID-19.

Heme is a member of the porphyrins family of cyclic tetrapyrroles and influences various cell processes and signalling pathways. Enzyme deficiencies in the heme biosynthetic pathway provoke rare human inherited metabolic diseases called porphyrias. Protein levels and activity of enzymes involved in the heme biosynthetic pathway and especially 5′-Aminolevulinate Synthase 1 are featured by 24-h rhythmic oscillations driven by the biological clock. Heme biosynthesis and circadian pathways intermingle with mutual modulatory roles. Notably, heme is a ligand of important cogs of the molecular clockwork, which upon heme binding recruit co-repressors and inhibit the transcription of numerous genes enriching metabolic pathways and encoding functional proteins bringing on crucial cell processes. Herein, we assessed mRNA levels of circadian genes in patients suffering from porphyrias and found several modifications of core clock genes and clock-controlled genes expression, associated with metabolic and electrolytic changes. Overall, our results show an altered expression of circadian genes accompanying heme biosynthesis disorders and confirm the need to deepen the knowledge of the mechanisms through which the alteration of the circadian clock circuitry could take part in determining signs and symptoms of porphyria patients and then again could represent a target for innovative therapeutic strategies.