For the sake of simplicity people use ‘Aging’ as a term to denote all the underlying processes behind this most complex biological phenomenon, experienced by most and happening in all human adults during their lifetime. Laypeople and scientists alike use the singular form, while in the light of recent research (think of the last couple decades) it’s obvious that there are individual and separate processes powering the ‘aging machine’ as time goes by. Our current scientific understanding lists at least 9 different processes. This view is expressed in the paper called Hallmarks of Aging, the mainstream academic summary published in the journal Cell.
The lists includes the following 9 hallmarks: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, altered intercellular communication.
Without going into details, the authors also imply causal relationships between some of the so called primary, antagonistic and integrative hallmarks above and emphasise the extensive interconnectedness between them. Nevertheless these are still separate processes ongoing and so I am going to use the plural term ‘agings’ from now on to capture the complexity involved much better. I am not suggesting a strong ‘aging vs. agings’ opposition here, just want to highlight the plurality and diversity behind these processes in order to make my point.
The good news for Gen P users is that the majority of these 9 processes have protein components, and since most of these are mega-processes involving different biological functions and pathways, they can have many protein participants, up to hundreds, thousands of proteins.
Here I would like to illustrate how Gen P molecular stories can already report quantitative information on many tens of proteins involved with at least 3 biological hallmarks: loss of proteostasis, mitochondrial dysfunction, altered intercellular communication.
Gen P’s Molecular Stories feature report on personalised abundances of groups of proteins involved in the same biological function and currently we have 15 such stories already and their numbers are growing.
1. Loss of proteostasis: currently we report on proteasome, ubiquitin and chaperone levels and that involves different proteins in each story, all of them detected in more than 90% of the samples. Gen P users can see how they perform compared to other samples, particularly in their age-adjusted group.
2. Mitochondrial dysfunction: we measure relative levels of different enzymes like ATP synthase and NADH dehydrogenase, all of them crucial components of the energy releasing electron transport chain involved in the vital metabolic process called oxidative phosphorylation.
3. Altered intercellular communication: one important process involved in this hallmark is termed ‘inflammaging’ and we know a lot more on the role now innate immunity plays in this process. Gen P measures at least 2 innate immunity components already: S100-A9, lactoferrin.
The point is since aging is really agings biologically underneath, it is unlikely that one magic bullet biomarker will be informative on the totality of the processes involved, however strong is that marker. Instead AgeCurve aims to deliver tens, hundreds of different molecular stories, molecular biopatterns if you like, that might not have strong information content separately, but aggregated together these patterns will really have more to say on the individual paces these agings are happening in the human body.
And we are just getting started.