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.

Loss of cytoskeletal proteostasis links dysregulation of cell size and mechanotransduction in mesenchymal stem cell senescence

“…These results highlight an additional – mechanical – impact that senescent cells could elicit on adjacent cells in their immediate environment, aside from the biochemical impact caused by the SASP. Indeed, “altered mechanical properties” was recently included as new hallmark of ageing (Schmauck-Medina et al , 2022).…”

Preconditioned Mesenchymal Stromal Cell-Derived Extracellular Vesicles (EVs) Counteract Inflammaging

“…The expression of the tetraspanin family members CD81 (BV421 Mouse Anti-Human CD81, BD Biosciences, 740079), CD63 (PE-Cy7 Mouse Anti-Human CD63, BD Biosciences, 561982) and CD9 (APC Mouse Anti-Human CD9, Biolegend, 312108) was analysed by non-conventional flow cytometry, as previously reported [ 27 ]. The separated EVs were analysed by western blot [ 3 ], using the following antibodies: anti-syntenin (1:1000 dilution, ab133267, Abcam), anti-flotillin-1 (1:10,000 dilution, ab41927, Abcam), anti-Grp94 (1:1000 dilution, ab238126, Abcam), and goat anti-rabbit/mouse secondary antibody (1:1500 dilution, Cell Signaling Technology, Danvers, MA, USA).…”

“…Biological aging can be defined as a loss of tissue’s physiological function both at the cellular and molecular level [ 1 ]. Different hallmarks, including genomic instability, telomere shortening, epigenetic alterations, mitochondrial dysfunction, senescence, and altered intercellular communication characterize biological aging [ 2 , 3 ]. Since the 1990s, a series of experimental data have indicated that the progressive increase in the concentration of circulating pro-inflammatory molecules was one of the primary features of human aging [ 4 , 5 , 6 ].…”

A Novel Strategy to Model Age-Related Cancer for Elucidation of the Role of Th17 Inflammaging in Cancer Progression

“…Aging represents a series of biological processes, including direct damage, accumulation of changes, cellular waste, errors, imperfect repairs, and responses [ 4 , 5 ]. These processes result in the familiar signs of aging and ultimately lead to the development of age-related diseases, such as Alzheimer’s disease, diabetes, cardiovascular disease, stroke, and cancer, eventually killing us.…”

“…Therefore, a recent research symposium, “New Hallmarks of Ageing,” was held, focusing on novel findings and the recontextualization of the nine hallmarks of aging. The new proposed hallmarks of aging [ 4 ] include autophagy, microbiome disturbance, altered mechanical properties, splicing dysregulation, and inflammation, among other emerging ones. Therefore, the amalgamation of the original and “new” hallmarks of aging will provide a more comprehensive explanation of aging and age-related diseases.…”