Can age suddenly hit you?
Imagine for a second that you are French. You bump into, say, a former teacher or partner on the street and notice they have suddenly (or markedly) aged. Later, you report the incident to a friend, saying “Oh là là, il/elle a pris un coup de vieux!”, which literally translates as “Oh my, s/he has been hit by ageing!”.
Of course, it is often easier to detect (shocking) ageing progress in others – especially when rarely encountered. But, at some point, most of us will have been confronted with an unflattering photograph or a brutally honest mirror image and wonder when ageing actually “struck” us.
Hmm, so does that mean that age hits us like a truck, or does it just creep up on us unnoticed until special circumstances open our eyes? Does age move in seasons? And if yes, does it have a detectable rhythm?
Steady progression versus waves of change
These are questions that have been preoccupying age researchers in recent years. While some ageing processes seem to unfurl at a relatively regular pace (such as telomere shortening or stem cell exhaustion), others seem to occur in fits and starts – in line with visible or invisible age transitions, such as the menopause or gut neurone loss respectively. Indeed, there is increasing new evidence that so-called “nonlinearities” may be more the norm than the exception when it comes to ageing.
A study in Nature Medicine (Lehallier et al., 2019) based on human plasma proteome profiles was e.g. able to show that there are waves of change in the proteome in the fourth, seventh and eighth decades of life. But until recently, there have been few studies on epigenetic non-linearities.
Mouse gut rhythms
A new paper published in Nature Communications (Olecka & al., 2024) focuses on gut ageing in mice through the methylation lens. The tissue was chosen because it offers a broad representation of the ageing panorama since it has numerous biological functions that “undergo age-related alterations” affecting “the emergence of age-related phenotypes in other organs, such as the brain, the heart, or the endocrine system”.
Just as with the proteome, the authors were able to detect abrupt methylation changes at two different periods – at early-to-midlife, and mid-to-late-life. The authors concluded that “The existence of transitions between discrete stages reveals the more controlled, or even programmed, nature of epigenetic aging and opens questions about the regulation and consequences of these abrupt changes” – especially on the functional level.
Ominous birthdays and non-linear ageing
Even more recently, a team writing in Nature Aging (Shen & al., 2024) conducted a human longitudinal study with a small Californian cohort of 108 participants. Their approach was an impressively deep and broad multi-omics profiling, involving among others proteomics, metabolomics and lipidomics testing – but no epigenomic trials.
Strikingly, they were able to pinpoint two big turning points in human ageing, featuring marked accelerations around the ages of 44 and 60. The 44-year-old transition is characterised by changes in cardiovascular disease, lipid and alcohol metabolism, whereas immune regulation, carbohydrate metabolism and kidney function shifts are typical of the 60-year-old landmark. Interestingly, the researchers found that most molecules (81.0%) investigated exhibited non-linear patterns. This seems to indicate that converging surges rather than slow and regular individual rhythms characterise the multi-pathway progression of ageing.
Insights into programmed ageing?
Obviously, these initial findings provide but a peek into the likely ramifications of non-linear ageing for humans. But if more human studies can be carried out, they may help to explain discrepancies in epigenetic ageing that may appear divorced from lifestyle factors or underlying health challenges. Moreover, they may open promising avenues for targeted interventions to slow down the ageing cycle!
This article was amended to incorporate the latest research (10.10.2024).
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Sources
Lehallier, B., Gate, D., Schaum, N. et al. "Undulating changes in human plasma proteome profiles across the lifespan". Nat Med 25, 1843–1850 (2019). https://doi.org/10038/s41591-019-0673-2. Online: https://www.nature.com/articles/s41591-019-0673-2
Olecka, M., van Bömmel, A., Best, L. et al. "Nonlinear DNA methylation trajectories in aging male mice". Nat Commun 15, 3074 (2024). https://doi.org/10.1038/s41467-024-47316-2. Online: https://www.nature.com/articles/s41467-024-47316-2
Shen, X., Wang, C., Zhou, X. et al. Nonlinear dynamics of multi-omics profiles during human aging. Nat Aging (2024). https://doi.org/10.1038/s43587-024-00692-2. Online: https://www.nature.com/articles/s43587-024-00692-2
Illustration
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