In our last post, we hinted at the fact that ageing goes way deeper than the wrinkles and the white hair or even the joint pain and impaired hearing we associate with getting older. So, are you ready to find out what skeletons rattle in the dark cupboard of ageing?
The authors of a seminal paper (López-Otín & al.) originally published in 2013 highlighted nine so-called “hallmarks of ageing” before updating them to twelve a decade later to accommodate more recent research. According to the authors, the common denominator of these deep transformations is “(1) their age-associated manifestation, (2) the acceleration of aging by experimentally accentuating them, and (3) the opportunity to decelerate, stop, or reverse aging by therapeutic interventions on them.” (2023).
Although these hallmarks can and usually do co-occur, they tend to evolve sequentially and from micro- to macro- or systemic damage. The primary hallmarks are located at the molecular level and seem to cause the initial damage. As the body reacts to this damage, the antagonistic hallmarks arise. Finally, the integrative hallmarks are signs that the body is increasingly (and systemically) overwhelmed.
So here are the 12 ultra-concisely defined hallmarks:
Primary hallmarks (causes of damage)
1. Genome instability (increased error-causing changes, mutations and rearrangements in the DNA)
2. Telomere attrition or “shortening” (shrinking of protective chromosomal caps)
3. Epigenetic alterations (changes in the biochemical switches around the DNA)
4. Loss of proteostasis (changes in the body’s protein management)
5. Disabled macroautophagy (malfunction of cellular waste disposal system)
Antagonistic hallmarks (responses to damage)
6. Deregulated nutrient sensing (body fails to detect and respond adequately to nutrients)
7. Mitochondrial dysfunction (the cell “energy plants” are less productive and generate more waste)
8. Cellular senescence (cells stop dividing but don’t die causing inflammation)
Integrative hallmarks (effects of uncontainable damage)
9. Stem cell exhaustion (when these key-cells fail to regenerate, tissues and organs fail to repair properly)
10. Altered intercellular communication (signalling pathways change, leading to abnormalities)
11. Chronic inflammation or “inflammaging” (chronic, low grade, systemic inflammation)
12. Dysbiosis (imbalance of microorganism communities in the gut)
So, these are the currently discernible processes behind the visible or palpable symptoms we associate with ageing. So, more may still come... The good news, however, is that we are not condemned to helplessly sit out the progressive destruction. Remember the hallmarks’ third common denominator we mentioned above? Ageing can be “decelerated, stopped, or reversed by therapeutic interventions on them”.
So, is that what “anti-ageing” is all about then? Find out in our next “short & sweet” episode!
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Sources and further reading
López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. "The hallmarks of aging". Cell. 2013 Jun 6;153(6):1194-217. doi: 10.1016/j.cell.2013.05.039. Online: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3836174/
López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. "Hallmarks of aging: An expanding universe." Cell. 2023 Jan 19; 186(2):243-278. doi: 10.1016/j.cell.2022.11.001. Online: https://www.cell.com/cell/fulltext/S0092-8674(22)01377-0
Illustration
pixabay & epiAge
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