suPAR can provide early indications of underlying inflammatory processes and potential health issues, making it an ideal biomarker when focusing on longevity

Healthy aging and longevity

There is an increasing interest in working with longevity and exploring ways to slow down premature aging by living a healthier, balanced life.

Many health clinics offering longevity programs have recently appeared worldwide to support this trend. The clinics have an increasingly broad appeal to people who want to improve or maintain good health as they age.

What is longevity?

It is one’s ability to live with a high degree of life quality (healthspan) for a long time (lifespan). The simplest way to do this is to postpone the development of diseases, thereby increasing healthspan and lifespan. By doing so, an individual can live more years with high well-being and quality of life.

In longevity Lifespan is often understood as the number of years in one's life, while healthspan is the quality of those years”

“suPAR informs on the general health of an individual. Is everything OK or should something be changed?”

Jesper Eugen-Olsen,
Chief Scientific Officer, ViroGates

How can the healthspan be increased?

Using molecular crystal balls can detect the early stages of disease development. This allows for the intervention and prevention of actual disease promptly.

suPAR – a molecular crystal ball

suPAR is a biomarker in the blood (Thunø M et al., 2009). The more suPAR you have in your blood, the faster you age (Rasmussen et al., 2021), and interestingly, people with high suPAR look older than people with low suPAR. It is essential to highlight that people with high suPAR have ongoing disease processes that can develop into major diseases such as cancer, diabetes, organ failure, or cardiovascular disease. That is precisely why keeping the suPAR level low is essential to prevent the development of various diseases.

What is suPAR?

uPAR is a measure of chronic inflammation in the body (Rasmussen et al., Review 2021). Chronic inflammation is a significant contributor to the aging process and age-related diseases. By measuring suPAR levels, one can gain insights into an individual’s overall inflammatory status, which impact their longevity.

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Elevated suPAR and accelerated aging

A groundbreaking study on suPAR as a longevity biomarker was published by Moffitt & Caspi group in 2021. Utilizing the famous Dunedin cohort, Line JH Rasmussen and coworkers measured suPAR in almost 1000 individuals 7 years after the initial measurement at 38 and then at age 45.

The researchers found that elevated suPAR was associated with an accelerated pace of biological aging across multiple organ systems (Figure 1A), older facial appearance (Figure 1B and Figure 2), and structural signs of older brain age. Moreover, participants with higher suPAR levels had a greater decline in cognitive function.

Furthermore, elevated suPAR was associated with multiple indicators of worsened functional capacity, including more physical limitations, poorer balance, weaker grip strength, slower gait speed, and poorer performance on the 2-minute step and chair-stand tests. Finally, improvements in health habits between ages 38 and 45 (smoking cessation or increased physical activity) were associated with less steep increases in suPAR levels over those years. The authors suggest that randomized clinical trials of anti-aging interventions intended to slow the course of aging could include suPAR as the outcome measure. The researchers propose that assessment of suPAR in midlife may create an opportunity for prevention, as individuals with elevated suPAR are at increased risk of developing diseases such as cancer, type 2 diabetes, cardiovascular disease, and, what’s more alarming are even at the risk of dying within the next 10 years (Tavenier J, et al. 2022, Haupt et al., 2019, Persson M et al., 2014, Eugen-Olsen J et al., 2010).

Figure 1 And B. Figure 1A shows that the mean pace of aging (years of physiological change per chronological year). Q refers to quintiles, e.g. Q5 are the 20% with highest suPAR, and they age with 1,2 year for every year the grow older. Figure 1B shows that those with highest suPAR also have older facial age. Facial age at age 45 was based on ratings by an independent panel of 8 raters of each participant’s facial photograph. The graph is from Rasmussen LJH, Caspi A, et al, 2021.

Figure 1 A and B. Figure 1A shows that the mean pace of aging (years of physiological change per chronological year). Q refers to quintiles, e.g. Q5 are the 20% with highest suPAR, and they age with 1,2 year for every year the grow older. Figure 1B shows that those with highest suPAR also have older facial age. Facial age at age 45 was based on ratings by an independent panel of 8 raters of each participant’s facial photograph. The graph is from Rasmussen LJH, Caspi A, et al, 2021.

Figure 2 shows a computer averaged picture of the 10 slowest, average, and fasted-aging cohort members. Individuals are aged 45 and born in the same hospital in Dunedin. Older facial age is correlated with higher suPAR (See figure 1B). Used with permission from Prof. Terrie Moffitt.

Figure 2 shows a computer averaged picture of the 10 slowest, average, and fasted-aging cohort members. Individuals are aged 45 and born in the same hospital in Dunedin. Older facial age is correlated with higher suPAR (See figure 1B). Used with permission from Prof. Terrie Moffitt.

What is the expected suPAR level of an individual?

suPAR increases throughout life as we age, but the increase is accelerated in individuals with unhealthy lifestyles. There are also gender differences in suPAR levels. You can calculate how the suPAR level of an individual is compared to other healthy individuals based on blood donors. You can achieve the score by entering the gender, age, and suPAR level into the algorithm, which will calculate your biological age and rate of aging.

What elevates suPAR?

suPAR is generally elevated in individuals with unhealthy lifestyles. For example, healthy diet, good amount of exercise and not smoking is associated with a low level of suPAR. As an example of the impact of unhealthy lifestyle on suPAR, in average smokers have 1 ng/ml higher level of suPAR compared to non-smokers. However not all smokers have the same risk, which will depend on the amount of suPAR measured in the blood. It has been proved that smokers with elevated suPAR level have an increased risk of developing e.g. lung cancer compared to smokers with low suPAR. Following smoking cessation, suPAR decreases within the next 4 weeks (Eugen-Olsen et al, 2016). Also, there is a linear association between how healthy you eat and your suPAR level (Tornkvist PBS et al, 2019).
suPAR is a sensitive marker that seems to capture and accumulate all the things that we already know are associated with a shorter lifespan. Interestingly, chronic inflammation as reflected in increased suPAR, is already increased at age 18 in children who have been exposed to adverse experiences, stress, and violence during childhood (Rasmussen LJH, Moffitt T et al, 2020). Also, stressful life events such as divorce, homelessness, being fired, death of a close relative, serious financial problems, physical or sexual attack or being jailed add to the suPAR level, with the more events, the higher suPAR (Bourassa KJ et al, 2021).

Guy smokeing which is not good for longevity

Focus on longevity can reduce suPAR and lower the risk of disease.

A Danish study measured the suPAR levels of 3225 Danes, which were followed for 5 years, and their lifestyle was observed. After 5 years, the measurement was repeated to see the changes in suPAR levels among individuals with varied lifestyle habits. Accordingly to the research findings, those who obtained a healthier lifestyle decreased or had a lower increase compared to those who continued an unhealthy lifestyle. The Danes were then followed for additional 6,8 years, and the suPAR level at their 5-year measurement was significantly associated with mortality (Haupt T et al., 2019). The conclusion of the research is significant- if suPAR is lowered, the risk is also reduced. Recent studies also show that suPAR in itself is a causal factor in the development of diseases such as atherosclerosis and kidney disease (Hindy G et al., 2022, Hayek SS et al., 2015). Thus, it makes sense to aim towards having as low suPAR as possible which can be achieved by leading a healthy, balanced lifestyle.

suPAR allows for early detection and intervention

suPAR can provide an early indication of underlying inflammatory processes and potential health issues, which is useful when focusing on longevity. Early detection of chronic inflammation may allow for early interventions and lifestyle modifications that can positively impact longevity. By monitoring suPAR levels over time, individuals and healthcare providers can assess the effectiveness of interventions and treatments designed to reduce inflammation and potentially extend lifespan.

  • Bourassa KJ, Rasmussen LJH, Danese A, Eugen-Olsen J, Harrington H, Houts R, Poulton R, Ramrakha S, Sugden K, Williams B, Moffitt TE, Caspi A. Linking stressful life events and chronic inflammation using suPAR (soluble urokinase plasminogen activator receptor). Brain Behav Immun. 2021 Oct;97:79-88.
  • Eugen-Olsen J, Andersen O, Linneberg A, Ladelund S, Hansen TW, Langkilde A, Petersen J, Pielak T, Møller LN, Jeppesen J, Lyngbaek S, Fenger M, Olsen MH, Hildebrandt PR, Borch-Johnsen K, Jørgensen T, Haugaard SB. Circulating soluble urokinase plasminogen activator receptor predicts cancer, cardiovascular disease, diabetes and mortality in the general population. J Intern Med. 2010 Sep;268(3):296-308.
  • Eugen-Olsen J, Ladelund S, Sørensen LT. Plasma suPAR is lowered by smoking cessation: a randomized controlled study. Eur J Clin Invest. 2016 Apr;46(4):305-11.
  • Haupt TH, Rasmussen LJH, Kallemose T, Ladelund S, Andersen O, Pisinger C, Eugen-Olsen J. Healthy lifestyles reduce suPAR and mortality in a Danish general population study. Immun Ageing. 2019 Jan 22;16:1.
  • Hayek SS, Sever S, Ko YA, Trachtman H, Awad M, Wadhwani S, Altintas MM, Wei C, Hotton AL, French AL, Sperling LS, Lerakis S, Quyyumi AA, Reiser J. Soluble Urokinase Receptor and Chronic Kidney Disease. N Engl J Med. 2015 Nov 12;373(20):1916-25.
  • Hindy G, Tyrrell DJ, Vasbinder A, Wei C, Presswalla F, Wang H, Blakely P, Ozel AB, Graham S, Holton GH, Dowsett J, Fahed AC, Amadi KM, Erne GK, Tekmulla A, Ismail A, Launius C, Sotoodehnia N, Pankow JS, Thørner LW, Erikstrup C, Pedersen OB, Banasik K, Brunak S, Ullum H, Eugen-Olsen J, Ostrowski SR; DBDS Consortium; Haas ME, Nielsen JB, Lotta LA; Regeneron Genetics Center; Engström G, Melander O, Orho-Melander M, Zhao L, Murthy VL, Pinsky DJ, Willer CJ, Heckbert SR, Reiser J, Goldstein DR, Desch KC, Hayek SS. Increased soluble urokinase plasminogen activator levels modulate monocyte function to promote atherosclerosis. J Clin Invest. 2022 Dec 15;132(24):e158788.
  • Persson M, Östling G, Smith G, Hamrefors V, Melander O, Hedblad B, Engström G. Soluble urokinase plasminogen activator receptor: a risk factor for carotid plaque, stroke, and coronary artery disease. Stroke. 2014 Jan;45(1):18-23.
  • Rasmussen LJH, Caspi A, Ambler A, Danese A, Elliott M, Eugen-Olsen J, Hariri AR, Harrington H, Houts R, Poulton R, Ramrakha S, Sugden K, Williams B, Moffitt TE. Association Between Elevated suPAR, a New Biomarker of Inflammation, and Accelerated Aging. J Gerontol A Biol Sci Med Sci. 2021 Jan 18;76(2):318-327.
  • Rasmussen LJH, Moffitt TE, Arseneault L, Danese A, Eugen-Olsen J, Fisher HL, Harrington H, Houts R, Matthews T, Sugden K, Williams B, Caspi A. Association of Adverse Experiences and Exposure to Violence in Childhood and Adolescence With Inflammatory Burden in Young People. JAMA Pediatr. 2020 Jan 1;174(1):38-47.
  • Rasmussen LJH, Petersen JEV, Eugen-Olsen J. Soluble Urokinase Plasminogen Activator Receptor (suPAR) as a Biomarker of Systemic Chronic Inflammation. Front Immunol. 2021 Dec 2;12:780641.
  • Tavenier J, Rasmussen LJH, Tolstrup J, Petersen J, Sobocki J, Pisinger C, Eugen-Olsen J, Gamst-Jensen H. Self-rated health and chronic inflammation are related and independently associated with hospitalization and long-term mortality in the general population. Sci Rep. 2022 Nov 17;12(1):19761.
  • Thunø M, Macho B, Eugen-Olsen J. suPAR: the molecular crystal ball. Dis Markers. 2009;27(3):157-72.
  • Törnkvist PBS, Haupt TH, Rasmussen LJH, Ladelund S, Toft U, Pisinger C, Eugen-Olsen J. Soluble urokinase plasminogen activator receptor is linearly associated with dietary quality and predicts mortality. Br J Nutr. 2019 Mar;121(6):699-708

Documented by 900+ peer-reviewed publications

Here you can find a summary of the research done on suPAR within different disease areas.

1000+

published suPAR studies in leading medical journals

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