Mitochondrial Dysfunction in Age‐Related Metabolic Disorders

Abstract

Aging is a natural biological process in living organisms characterized by receding bioenergetics. Mitochondria are crucial for cellular bioenergetics and thus an important contributor to age‐related energetics deterioration. In addition, mitochondria play a major role in calcium signaling, redox homeostasis, and thermogenesis making this organelle a major cellular component that dictates the fate of a cell. To maintain its quantity and quality, mitochondria undergo multiple processes such as fission, fusion, and mitophagy to eliminate or replace damaged mitochondria. While this bioenergetics machinery is properly protected, the functional decline associated with age and age‐related metabolic diseases is mostly a result of failure in such protective mechanisms. In addition, metabolic by‐products like reactive oxygen species also aid in this destructive pathway. Mitochondrial dysfunction has always been thought to be associated with diseases. Moreover, studies in recent years have pointed out that aging contributes to the decay of mitochondrial health by promoting imbalances in key mitochondrial‐regulated pathways. Hence, it is crucial to understand the nexus of mitochondrial dysfunction in age‐related diseases. This review focuses on various aspects of basic mitochondrial biology and its status in aging and age‐related metabolic diseases.

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

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Disease-specific plasma levels of mitokines FGF21, GDF15, and Humanin in type II diabetes and Alzheimer’s disease in comparison with healthy aging

“…Mitochondria are fundamental to produce cellular energy currency and are involved in a variety of metabolic pathways. The aging process is characterized by a progressive mitochondrial dysfunction accompanied by increased production of Reactive Oxygen Species (ROS), considered as one of the key hallmarks of a variety of several age-related pathologies, such as neurodegenerative diseases, metabolic diseases, cardiovascular diseases, and cancer [ 2 , 3 ]. Mitochondrial dysfunction represents a stress condition that elicits an adaptive response which is not confined into the cell but can also spread to distal tissues by means of soluble mediators indicated as mitokines [ 4 ].…”

Redox and mTOR-dependent regulation of plasma lamellar calcium influx controls the senescence-associated secretory phenotype

“…Since mitochondria are the master regulators of cellular metabolism, it is not surprising that the key underlying factor among these metabolism diseases is mitochondrial dysfunction. 73 The quality and quantity of mitochondria are essential to maintain the energetic balance to meet tissue-specific energy demand, as well as to maintain healthy ROS production for signaling purposes. Mitochondria maintain their health through dynamic processes, including mitochondrial fusion, which helps in fusing mitochondria to enhance the energy production, and mitochondrial fission, which helps segregating the damaged mitochondria.…”