Longevity Briefs: Quantifying Biological Age Across Diverse Tissues

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The idea that some of us age faster than others – long an intuitive notion captured by phrases like “young-for-their-age” or “hasn’t-aged-well” – has been put on firmer footing in the last few years with the invention of methylation clocks.

These clocks measure changes in the epigenome with ageing, and purport to measure your biological age. Biological age differs from chronological age (simply put, the number of times you’ve careened around the sun) by attempting to capture how intrinsically old (or young!) your tissues are. The two measures become uncoupled whenever genetics, lifestyle, environment, and disease intervene.

Why Is This Research Important?

One criticism of the clocks however is that they make a claim about systemic (whole-body) age, while only sampling from a small subset of cells (typically blood or skin cells). While there is evidence that these clocks correlate well with the rest of the body, we should consider the possibility that some subsets of the body age more or less rapidly than others, and this might be significant for disease risk and prognosis.

The latest (and largest) exploration of this line of thought comes to us out of China. Titled Distinct Biological Ages of Organs and Systems Identified From a Multi-omics Study by Nie et al., the study examines 4066 individuals for 402 different multi-omic measures of ageing and disease. Their key findings are a dramatic confirmation of just how diverse ageing is within different tissues, organs, and systems!

What Did The Researchers Do?

The researchers took a “deep-phenotyping” approach, which aims to capture in-depth measurements of health by using multi-omics data. To do this, the researchers recruited 4066 volunteers, aged 20-45, from Shenzhen, China. They then proceeded to measure 403 different variables on each volunteer; including metabolic, biochemical, immune, body composition, physical fitness, electroencephalography, facial skin, and gut microbiome features.

These measurements were then grouped into 9 categories: cardiovascular, renal, liver, sex hormones, skin features, nutrition & metabolic features, immune-related, physical fitness-related, and gut-microbiome.

Following this, the researchers singled out the measures that correlated with age across their sample and generated a ‘Biological Age’ score for each of the 9 categories above – the idea being that some values of these tests correlate with a younger chronological age, and then after finding this correlation, we can solve the inverse problem and infer, from a set of measurement values, a person’s Biological Age.

The researchers then go on to analyse this data, as well as to investigate the genetic basis of some of the effects they note in their analysis.

Key Takeaways From This Research:

People age differently, and so do their organs!

• Within a single person, one organ or system may age faster than others
• The researchers identified 2 distinct groups of people, those ageing faster than their chronological age suggests, and those ageing slower – giving experimental evidence to the long-held folk belief that some people “age well”!
• The biological ages for most systems are correlated, but in general, they can decouple, and some organs may age faster than others within a single person
• It’s possible to predict disease severity and risk of a given organ system from that system’s measured biological age – this is important because
• There appear to be some systemic genetic effects that lead to general faster or slower ageing, which is overlaid on top of organ-specific ageing factors