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.
Highlights
The Nine Hallmarks of AgingAging is a multifactorial and complex process, affecting organisms at the molecular, cellular, tissue, and system levels (Gems and Partridge, 2013; Cohen, 2018)
Aging and age-related diseases are often accompanied by a lack of mitochondrial fusion, which leads to fragmented mitochondria (Chen et al, 2007; Houtkooper et al, 2013; Sharma et al, 2019), and altering mitochondrial dynamics of fission and fusion can extend lifespan in worms (Weir et al, 2017; Liu et al, 2020b)
We look beyond mitochondrial dysfunction as an individual hallmark and explore how these mitochondrial processes and age-related deteriorations interrelate and communicate with the other hallmarks of aging
Summary
Aging is a multifactorial and complex process, affecting organisms at the molecular, cellular, tissue, and system levels (Gems and Partridge, 2013; Cohen, 2018). This progressive deterioration throughout life leads to age-related diseases such as cardiovascular diseases, cancer, osteoarthritis, diabetes mellitus type II and neurodegenerative diseases such as Alzheimer’s Disease (AD) and Parkinson’s Diseases (PD) (López-Otín et al, 2013; Franceschi et al, 2018). With the aim of uncovering mechanisms of aging and discovering interventions that promote healthier aging, scientists have utilized model organisms from across the phylogenetic tree. Frontiers in Cell and Developmental Biology | www.frontiersin.org van der Rijt et al
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