Integrating the Hallmarks of Aging Throughout the Tree of Life: A Focus on Mitochondrial Dysfunction

Abstract

Since the identification and definition of the hallmarks of aging, these aspects of molecular and cellular decline have been most often described as isolated or distinct mechanisms. However, there is significant evidence demonstrating interplay between most of these hallmarks and that they have the capacity to influence and regulate one another. These interactions are demonstrable across the tree of life, yet not all aspects are conserved. Here, we describe an integrative view on the hallmarks of aging by using the hallmark “mitochondrial dysfunction” as a focus point, and illustrate its capacity to both influence and be influenced by the other hallmarks of aging. We discuss the effects of mitochondrial pathways involved in aging, such as oxidative phosphorylation, mitochondrial dynamics, mitochondrial protein synthesis, mitophagy, reactive oxygen species and mitochondrial DNA damage in relation to each of the primary, antagonistic and integrative hallmarks. We discuss the similarities and differences in these interactions throughout the tree of life, and speculate how speciation may play a role in the variation in these mechanisms. We propose that the hallmarks are critically intertwined, and that mapping the full extent of these interactions would be of significant benefit to the aging research community.

An energetics perspective on geroscience: mitochondrial protonmotive force and aging

“…Mitochondrial dysfunction is recognized as one of the nine "hallmarks of aging" [3], and a case can be made that mitochondrial dysfunction may causally contribute to each of the other aging hallmarks [4,5] (Fig. 1).…”

Smac/DIABLO can predict postoperative delirium in elderly patients after cardiac surgery : A prospective nested case-control study

“…Mitochondria, as the major organelles that produce energy in the cell, was named "powerhouse". In general, mitochondrial function is impaired and release toxic proteins when apoptotic stimuli act on cells, manifests as decreased ATP supply, overproduced reactive oxygen species (ROS), and a series of cysteine-aspartate proteases (caspases) activation [9,20]. Recently, mitochondrial fusion/fission dynamics imbalance contributes to delirium-like behavior in aged mice has been reported [21].…”

“…Mitochondria as the most fragile injured organelles to hypoxia, primarily take place morphological and functional changes, such as mitochondrial fission-fusion disorder, membrane potential decrease, proteins of mitochondrial intercristae efflux into the cytoplasm. Mitochondrial dysfunction, viewed as hallmarks of aging and disturbed intracellular oxidative phosphorylation, has been reported as an early pathogenic event of Alzheimer's disease and involved in the pathogenesis of delirium-like behavior in aged mice [9,10]. Mitochondria, not only provide the site for intracellular oxidative phosphorylation, but also involve in cell information transmission, apoptosis, and regulating cell growth and cycle.…”

Superoxide Dismutase 2 (SOD2) in Vascular Calcification: A Focus on Vascular Smooth Muscle Cells, Calcification Pathogenesis, and Therapeutic Strategies

“…Mitochondrial dysfunction leads to the failure of this organelle to generate adequate ATP to meet cellular demand, culminating in energy failure, compromised cellular viability, and tissue remodeling. The spectrum of mitochondrial dysfunction includes but is not limited to mitochondrial dynamic perturbation, mitochondrial protein synthesis impairment, reduced mitophagy, uprising mitochondrial reactive oxygen species (mtROS), and mitochondrial DNA damages [ 14 ]. This phenomenon has been described in multiple degenerative disorders, ranging from malignancy, neurodegenerative disorders, DM, and cardiovascular diseases.…”