I'm not sure that I am entirely convinced, but here researchers argue that age-related mitochondrial dysfunction should be addressed in different ways in different organs. Certainly it is true that delivery strategies for many types of therapy must be different for different organs, and this is a major issue for cell therapies and gene therapies. But ways to improve mitochondrial function should, in principle, be beneficial wherever applied and whatever the present status of mitochondrial function.
As cellular power plants and critical production sites of reactive oxygen species (ROS), mitochondria play a pivotal role in the process of aging, and their dysfunction has been associated with age-related diseases. Mitochondria profoundly influence their cellular environment through their central roles in ATP production, ROS generation, ion homeostasis, and signaling events. Besides, once released into the extracellular space, several mitochondrial constituents, such as mitochondrial nucleic acids or metabolites, can act as danger-associated molecular patterns (DAMPs) that trigger innate immune responses and inflammation. Similarly, mitochondria can also be shed by stressed cells in extracellular vesicles, which carry DAMPs and can act in a paracrine and endocrine manner.
As cells age, mitochondria experience a decline in function, characterized by mitochondrial DNA mutations, increased oxidative stress, DAMP formation, decreased mitochondrial energy conversion, and hampered mitochondrial turnover and dynamics. Consequently, understanding the multifaceted roles of mitochondria is fundamental in deciphering their impact on the process of aging and their potential as anti-aging targets.
The current review examines recent advances in understanding the interplay between mitochondrial dysfunction and organ-specific aging. Thereby, we dissect molecular mechanisms underlying mitochondrial impairment associated with the deterioration of organ function, exploring the role of mitochondrial DNA, reactive oxygen species homeostasis, metabolic activity, damage-associated molecular patterns, biogenesis, turnover, and dynamics. We also highlight emerging therapeutic strategies in preclinical and clinical tests that are supposed to rejuvenate mitochondrial function, such as antioxidants, mitochondrial biogenesis stimulators, and modulators of mitochondrial turnover and dynamics. Furthermore, we discuss potential benefits and challenges associated with the use of these interventions, emphasizing the need for organ-specific approaches given the unique mitochondrial characteristics of different tissues.
Link: https://doi.org/10.1016/j.pharmthera.2024.108710
View the full article at FightAging
