Chapter 176
Changing Aging — 13
The problem with the body-wide clocks is that some people are heart agers, while others are brain or kidney agers. Tony Wyss-Coray of Stanford University investigated this, assessing nearly five thousand plasma proteins for eleven organs in 5,676 people (from five independent cohorts) across the human lifespan. The study confirmed that our intrabody aging by organ and system is quite heterogeneous. Unique protein clusters tracked with each organ. One in five individuals had at least one organ in age acceleration, but only about 2 percent of people were multiorgan fast agers. Each organ’s markers were predictive of adverse health outcomes over fifteen years of follow-up in the same domain, such as heart aging and a fivefold rate of heart failure or brain aging markers predicting a higher risk of Alzheimer’s disease. Muscle aging predicted impairment of gait, while kidney aging predicted hypertension and the metabolic syndrome. The gap from organ age to chronological age of the person was associated with increased mortality during the extended follow-up period (fig. 12.4 top panel).
These findings were subsequently replicated and extended in two studies using the UK Biobank resource. In nearly fifty-three thousand UK Biobank participants, with measurement of three thousand plasma proteins, organ-specific aging clocks and impact of interventions were identified. For example, alcohol accelerated aging of the brain, kidney, and intestine. The effects of smoking were across the board—not just lung but also brain, immune system, liver, kidney, and intestine. Men were biologically older and tended to age faster than women across the various organs. Foods like muesli, oily fish, and raw salad were associated with slower multiorgan aging, whereas it was the opposite for sugar-sweetened beverages, white bread, and savory snacks. Ludger Geominne of Harvard Medical School and colleagues concluded the following: “These findings suggest that future antiaging interventions should not only target organismal aging, but could also be tailored towards the oldest organs, calling for a more personalized approach towards anti-aging interventions.”
Figure 12.4. Organ clock gap (proteomic age versus chronologic age) for prediction of death risk by organ type aging (top panel) and number of organs with accelerated aging, normal aging, and reduced brain and immune system aging (bottom panel). Adapted from Hamilton Se-Hwee Oh et al., “Organ aging signatures in the plasma proteome track health and disease,” Nature 624, no. 7990 (December 2023): 164–72, https://doi.org/10.1038/s41586-023-06802-1 (top panel) and Hamilton Se-Hwee Oh et al., “Plasma proteomics in the UK biobank reveals youthful brains and immune systems promote healthspan and longevity,” bioRxiv (June 2024) (bottom panel).
The other study of eleven organ system clocks in more than forty-four thousand UK Biobank participants, with about three thousand plasma proteins, was quite illuminating, not just for extending the finding that each organ’s clock predicted diseases, such as accelerated brain aging and near doubling risk of Alzheimer’s disease, but also for interventions like smoking, exercise, hormone replacement therapy, and supplements. Hormone replacement therapy was associated with reduced aging of the immune system, brain, liver, and arteries. The impressive added findings were that a youthful brain and immune system were uniquely associated with longevity (fig. 12.4 bottom panel). In contrast, the more organs exhibiting accelerated aging, the worse the survival.