Mitochondrial health quality control: measurements and interpretation in the framework of predictive, preventive, and personalized medicine.

Mitochondria are the "gatekeeper" in a wide range of cellular functions, signaling events, cell homeostasis, proliferation, and apoptosis. Consequently, mitochondrial injury is linked to systemic effects compromising multi-organ functionality. Although mitochondrial stress is common for many pathomechanisms, individual outcomes differ significantly comprising a spectrum of associated pathologies and their severity grade. Consequently, a highly ambitious task in the paradigm shift from reactive to predictive, preventive, and personalized medicine (PPPM/3PM) is to distinguish between individual disease predisposition and progression under circumstances, resulting in compromised mitochondrial health followed by mitigating measures tailored to the individualized patient profile. For the successful implementation of PPPM concepts, robust parameters are essential to quantify mitochondrial health sustainability. The current article analyses added value of Mitochondrial Health Index (MHI) and Bioenergetic Health Index (BHI) as potential systems to quantify mitochondrial health relevant for the disease development and its severity grade. Based on the pathomechanisms related to the compromised mitochondrial health and in the context of primary, secondary, and tertiary care, a broad spectrum of conditions can significantly benefit from robust quantification systems using MHI/BHI as a prototype to be further improved. Following health conditions can benefit from that: planned pregnancies (improved outcomes for mother and offspring health), suboptimal health conditions with reversible health damage, suboptimal life-style patterns and metabolic syndrome(s) predisposition, multi-factorial stress conditions, genotoxic environment, ischemic stroke of unclear aetiology, phenotypic predisposition to aggressive cancer subtypes, pathologies associated with premature aging and neuro/degeneration, acute infectious diseases such as COVID-19 pandemics, among others.

Age-related mitochondrial dysfunction as a key factor in COVID-19 disease.

SARS-CoV-2 causes a severe pneumonia (COVID-19) that affects essentially elderly people. In COVID-19, macrophage infiltration into the lung causes a rapid and intense cytokine storm leading finally to a multi-organ failure and death. Comorbidities such as metabolic syndrome, obesity, type 2 diabetes, lung and cardiovascular diseases, all of them age-associated diseases, increase the severity and lethality of COVID-19. Mitochondrial dysfunction is one of the hallmarks of aging and COVID-19 risk factors. Dysfunctional mitochondria is associated with defective immunological response to viral infections and chronic inflammation. This review discuss how mitochondrial dysfunction is associated with defective immune response in aging and different age-related diseases, and with many of the comorbidities associated with poor prognosis in the progression of COVID-19. We suggest here that chronic inflammation caused by mitochondrial dysfunction is responsible of the explosive release of inflammatory cytokines causing severe pneumonia, multi-organ failure and finally death in COVID-19 patients. Preventive treatments based on therapies improving mitochondrial turnover, dynamics and activity would be essential to protect against COVID-19 severity.