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1.
Int J Mol Sci ; 23(20)2022 Oct 14.
Article in English | MEDLINE | ID: covidwho-2071511

ABSTRACT

Caloric restriction promotes longevity in multiple animal models. Compounds modulating nutrient-sensing pathways have been suggested to reproduce part of the beneficial effect of caloric restriction on aging. However, none of the commonly studied caloric restriction mimetics actually produce a decrease in calories. Sodium-glucose cotransporter 2 inhibitors (SGLT2-i) are a class of drugs which lower glucose by promoting its elimination through urine, thus inducing a net loss of calories. This effect promotes a metabolic shift at the systemic level, fostering ketones and fatty acids utilization as glucose-alternative substrates, and is accompanied by a modulation of major nutrient-sensing pathways held to drive aging, e.g., mTOR and the inflammasome, overall resembling major features of caloric restriction. In addition, preliminary experimental data suggest that SGLT-2i might also have intrinsic activities independent of their systemic effects, such as the inhibition of cellular senescence. Consistently, evidence from both preclinical and clinical studies have also suggested a marked ability of SGLT-2i to ameliorate low-grade inflammation in humans, a relevant driver of aging commonly referred to as inflammaging. Considering also the amount of data from clinical trials, observational studies, and meta-analyses suggesting a tangible effect on age-related outcomes, such as cardiovascular diseases, heart failure, kidney disease, and all-cause mortality also in patients without diabetes, here we propose a framework where at least part of the benefit provided by SGLT-2i is mediated by their ability to blunt the drivers of aging. To support this postulate, we synthesize available data relative to the effect of this class on: 1- animal models of healthspan and lifespan; 2- selected molecular pillars of aging in preclinical models; 3- biomarkers of aging and especially inflammaging in humans; and 4- COVID-19-related outcomes. The burden of evidence might prompt the design of studies testing the potential employment of this class as anti-aging drugs.


Subject(s)
COVID-19 , Diabetes Mellitus, Type 2 , Sodium-Glucose Transporter 2 Inhibitors , Animals , Humans , Sodium-Glucose Transporter 2 Inhibitors/pharmacology , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Sodium-Glucose Transporter 2 , Hypoglycemic Agents/pharmacology , Hypoglycemic Agents/therapeutic use , Inflammasomes , Drug Repositioning , Diabetes Mellitus, Type 2/drug therapy , Aging , Glucose/therapeutic use , TOR Serine-Threonine Kinases , Sodium , Ketones/therapeutic use , Fatty Acids/therapeutic use
2.
iScience ; 24(8): 102898, 2021 Aug 20.
Article in English | MEDLINE | ID: covidwho-1322153

ABSTRACT

The clinical benefit of convalescent plasma (CP) for patients with coronavirus disease (COVID)-19 is still debated. In this systematic review and meta-analysis, we selected 10 randomized clinical trials (RCTs) and 15 non-randomized studies (total number of patients = 22,591) of CP treatment and evaluated two different scenarios: (1) disease stage of plasma recipients and (2) donated plasma antibody titer, considering all-cause mortality at the latest follow-up. Our results show that, when provided at early stages of the disease, CP significantly reduced mortality: risk ratio (RR) 0.72 (0.68, 0.77), p < 0.00001, while provided in severe or critical conditions, it did not (RR: 0.94 [0.86, 1.04], p = 0.22). On the other hand, the benefit on mortality was not increased by using plasma with a high-antibody titer compared with unselected plasma. This meta-analysis might promote CP usage in patients with early-stage COVID-19 in further RCTs to maximize its benefit in decreasing mortality, especially in less affluent countries.

3.
Diabetes Metab Res Rev ; 38(1): e3476, 2022 01.
Article in English | MEDLINE | ID: covidwho-1245386

ABSTRACT

AIMS: Diabetes is emerging as a risk factor for coronavirus disease (COVID)-19 prognosis. However, contradictory findings have been reported regarding the impact of glycaemic control on COVID-19 outcome. The aim of this meta-analysis was to explore the impact of hospital pre-admission or at-admission values of HbA1c on COVID-19 mortality or worsening in patients with diabetes. MATERIALS AND METHODS: We searched PubMed, Embase and Scopus up to 30th December 2020. Eligibility criteria for study selection were the following: (1)enrolling patients with any form of diabetes mellitus and hospitalized for COVID-19 and (2) reporting data regarding HbA1c values before infection or at hospital admission in relation to COVID-19 mortality or worsening. Descriptive statistics, HbA1c values, odds ratios (ORs) and hazard ratios were extracted from seven observational studies and generic inverse variance (random effects) of OR was used to estimate the effect of HbA1c on COVID-19 outcome. RESULTS: HbA1c was linearly associated with an increased COVID-19 mortality or worsening when considered as a continuous variable (OR 1.01 [1.01, 1.01]; p < 0.00001). Similarly, when analysing studies providing the number of events according to the degree of glycaemic control among various strata, a significantly increased risk was observed with poor glycaemic control (OR 1.15 [1.11, 1.19]; p < 0.00001), a result corroborated by sensitivity analysis. CONCLUSIONS: Notwithstanding the large heterogeneity in study design and patients' characteristics in the few available studies, data suggest that patients with diabetes and poor glycaemic control before infection might have an increased risk of COVID-19 related mortality.


Subject(s)
COVID-19 , Glycated Hemoglobin A , COVID-19/mortality , Diabetes Mellitus , Glycated Hemoglobin A/analysis , Humans , Hyperglycemia , Risk Assessment
4.
Lancet Healthy Longev ; 2(4): e191, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1164732
5.
Trends Immunol ; 42(1): 18-30, 2021 01.
Article in English | MEDLINE | ID: covidwho-1065237

ABSTRACT

Severe infection with severe acute respiratory syndrome coronavirus (SARS-CoV)-2 is characterized by massive cytokine release and T cell loss. The exaggerated host immune response, incapable of viral clearance, instead aggravates respiratory distress, as well as cardiac, and/or damage to other organs. The mortality pattern of SARS-CoV-2 infection, higher in older versus younger adults and almost absent in children, is possibly caused by the effects of age and pre-existing comorbidities on innate and adaptive immunity. Here, we speculate that the abnormal and excessive immune response to SARS-CoV-2 infection partly depends on T cell immunological memory, which is more pronounced in adults compared with children, and may significantly contribute to immunopathology and massive collateral damage in coronavirus disease 2019 (COVID-19) patients.


Subject(s)
Adaptive Immunity/immunology , COVID-19/immunology , Immunity, Innate/immunology , SARS-CoV-2/immunology , T-Lymphocytes/immunology , COVID-19/prevention & control , COVID-19/virology , Cytokines/immunology , Cytokines/metabolism , Humans , Immunologic Memory/immunology , Models, Immunological , SARS-CoV-2/physiology , T-Lymphocyte Subsets/cytology , T-Lymphocyte Subsets/immunology , T-Lymphocyte Subsets/metabolism , T-Lymphocytes/cytology , T-Lymphocytes/metabolism
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