Background： Aging is a complex systems level problem that needs a systems level solution. However, system models of aging and longevity, although urgently needed, are still lacking, largely due to the paucity of conc...Background： Aging is a complex systems level problem that needs a systems level solution. However, system models of aging and longevity, although urgently needed, are still lacking, largely due to the paucity of conceptual frameworks for modeling such a complex process. Results： We propose that aging can be viewed as a decline in system capacity, defined as the maximum level of output that a system produces to fulfill demands. Classical aging hallmarks and anti-aging strategies can be well-aligned to system capacity. Genetic variants responsible for lifespan variation across individuals or species can also be explained by their roles in system capacity. We further propose promising directions to develop systems approaches to modulate system capacity and thus extend both healthspan and lifespan. Conclusions： The system capacity model of aging provides an opportunity to examine aging at the systems level. This model predicts that the extent to which aging can be modulated is normally limited by the upper bound of the system capacity of a species. Within such a boundary, aging can be delayed by moderately increasing an individual＇s system capacity. Beyond such a boundary, increasing the upper bound is required, which is not unrealistic given the unlimited potential of regenerative medicine in the future, but it requires increasing the capacity of the whole system instead of only part of it.展开更多
基金We thank Yizhen Yan for illustration suggestions and acknowledge supports from China Ministry of Science and Technology 2015CB964803 and 2016YFE0108700 and the National Natural Science Foundation of China 91329302, 31210103916 and 91519330, and Chinese Academy of Sciences XDB19020301 and XDA01010303 to J.D.J.H.
文摘Background： Aging is a complex systems level problem that needs a systems level solution. However, system models of aging and longevity, although urgently needed, are still lacking, largely due to the paucity of conceptual frameworks for modeling such a complex process. Results： We propose that aging can be viewed as a decline in system capacity, defined as the maximum level of output that a system produces to fulfill demands. Classical aging hallmarks and anti-aging strategies can be well-aligned to system capacity. Genetic variants responsible for lifespan variation across individuals or species can also be explained by their roles in system capacity. We further propose promising directions to develop systems approaches to modulate system capacity and thus extend both healthspan and lifespan. Conclusions： The system capacity model of aging provides an opportunity to examine aging at the systems level. This model predicts that the extent to which aging can be modulated is normally limited by the upper bound of the system capacity of a species. Within such a boundary, aging can be delayed by moderately increasing an individual＇s system capacity. Beyond such a boundary, increasing the upper bound is required, which is not unrealistic given the unlimited potential of regenerative medicine in the future, but it requires increasing the capacity of the whole system instead of only part of it.
