TY - JOUR
T1 - Integrating the Hallmarks of Aging Throughout the Tree of Life: A Focus on Mitochondrial Dysfunction
AU - van der Rijt, Sanne
AU - Molenaars, Marte
AU - McIntyre, Rebecca L.
AU - Janssens, Georges E.
AU - Houtkooper, Riekelt H.
N1 - Copyright © 2020 van der Rijt, Molenaars, McIntyre, Janssens and Houtkooper.
PY - 2020/11/26
Y1 - 2020/11/26
N2 - 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.
AB - 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.
KW - aging
KW - hallmarks of aging
KW - interplay
KW - mitochondria
KW - tree of life
UR - http://www.scopus.com/inward/record.url?scp=85097411711&partnerID=8YFLogxK
U2 - https://doi.org/10.3389/fcell.2020.594416
DO - https://doi.org/10.3389/fcell.2020.594416
M3 - Review article
C2 - 33324647
SN - 2296-634X
VL - 8
JO - Frontiers in cell and developmental biology
JF - Frontiers in cell and developmental biology
M1 - 594416
ER -