A guide to healthy aging

15 Oct 2021

On 14 October 2021 The Lancet Healthy Longevity (doi: 10.1016/S2666-7568(21)00226-9) published an article focusing on a urinary proteomic aging clock that reflects biological age as compared to chronological age and opens new horizons in preventive medicine.

A consortium of researchers belonging to the Research Institute Alliance for the Promotion of Preventive Medicine (Mechelen, Belgium), Mosaiques-Diagnostiques (Hannover, Germany), and the Universities of Hasselt and Leuven in Belgium and other European Research Institutes published today an article in The Lancet Healthy Longevity that shows data underpinning the groundbreaking idea that analysis of a small urine sample provides information on a person’s biological age and the probability of that a person will age healthy. That biological age differs from chronological age is well known. Everybody knows people who look older than their true age or elderly whose body kept a young demeanor for years on end. The researchers built their case on the fact that circulating blood passes through all vital organs and therefore carries molecules, which reflect the health of these organs and by extension of the whole human body. After filtration, these molecules appear in the urine. The major part of these molecules are fragments of proteins, which represent the building blocks of all cells and the machinery that keeps cell thriving and alive. Over 21,000 of such fragments can be measured on a 10 milliliter urine sample. These fragments can be characterized, so that the proteins from which they are derived can be identified, which in turn allows reconstructing the molecular pathways that reflect malfunction of organs even at a stage when a person is still apparently healthy, but at risk of developing age-related diseases, such as heart failure or renal disease. Using data from a Flemish population study collected from 1985 until 2019, the research established a urinary marker consisting of 54 protein fragments derived from 17 key proteins. In the population study, the so-derived aging clock was replicated by subdividing the study participants in two groups, of which one was examined twice at an interval of 4 years. The urinary marker was associated with risk factors associated with unhealthy aging, such as for instance high blood pressure, dysregulation of the fat metabolism or obesity. Independent of the participants’ age, the urinary aging clock also predicted total and cardiovascular mortality and osteoporosis. The urinary aging clock was also validated in patients with diabetes, COVID-19 infection or kidney disease by showing that the marker was indicative of a higher biological age than chronological age. Of particular interest was that that most urinary fragments making up the aging clock were derived from collagen, which forms chains that in normal conditions support the structural integrity of organs and the human body as a whole, for instance as a major constituent of bones. When organs are injured, they undergo a repair process, whereby collagens are produced. However, injury continues, such as for instance in myocardial infarction, heart failure or kidney disease, there is overproduction of collagens, which lead to deterioration of organ function and accelerated aging. The Lancet article showed that the aging clock, despite the increased production of collagen in disease, is characterized by less urinary excretion of collagen fragments. Some drugs are available that inhibit the production of collagen, but they also reduce the normal wound healing capacity. The new findings suggests that emphasis should shift to a search of drugs that stimulate collagen breakdown. This is a large unmet need, because globally 45% of all natural deaths in high-income countries are attributable to excess collagen production, such as seen in all chronic diseases associated with advancing age. In most countries over 80% of the health care budgets are spent in treating disabling and commonly irreversible disease. The clinical application of the urinary aging clock would enable shifting focus from treating established disease to prevention. The timely management of risk factors requires much less resources that the invasive therapies required to manage advanced stages of heart or renal disease, the use of intensive care units, the care of musculoskeletal disorders and the traumatic therapies currently applied for cancer. The aging clock developed and validated by the research consortium is the first urinary marker reflecting a person’s general health and probability of healthy versus unhealthy aging. Other urinary markers developed until to date are disease-specific and quantify the risk of patients with silent disease to develop heart failure or kidney disease or the probability that COVID 19 patients will require intensive care or will not survive the infection.