suPAR in longevity

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 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.

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).

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.