New hallmarks of ageing: a 2022 Copenhagen ageing meeting summary

Abstract

Genomic instability, telomere attrition, epigenetic alterations, mitochondrial dysfunction, loss of proteostasis, deregulated nutrient-sensing, cellular senescence, stem cell exhaustion, and altered intercellular communication were the original nine hallmarks of ageing proposed by López-Otín and colleagues in 2013. The proposal of these hallmarks of ageing has been instrumental in guiding and pushing forward research on the biology of ageing. In the nearly past 10 years, our in-depth exploration on ageing research has enabled us to formulate new hallmarks of ageing which are compromised autophagy, microbiome disturbance, altered mechanical properties, splicing dysregulation, and inflammation, among other emerging ones. Amalgamation of the 'old' and 'new' hallmarks of ageing may provide a more comprehensive explanation of ageing and age-related diseases, shedding light on interventional and therapeutic studies to achieve healthy, happy, and productive lives in the elderly.

Keywords: autophagy; hallmarks of ageing; healthspan; longevity; neurodegeneration.

Figure 1

New hallmarks of ageing. The figure enumerates the original hallmarks of ageing plus the five new proposed hallmarks that were discussed in the symposium. To qualify as a hallmark, the processes should change with biological age not simply in a correlative manner, but have a causal role. Hence interventions that address the hallmarks should, at the very least, halt further detrimental aspects of ageing, and preferably improve phenotypes associated with ageing.

Figure 2

The force of natural selection in ageing. The force that selects different traits declines as a function of age after reproductive age. Natural selection benefits survival to maturity and reproduction. Therefore, traits that present harmful effects late in life (selection shadow) will likely have already been passed to the next generation. The figure was generated based on the reference [34].