Blood Biomarkers as Predictors of Longevity

A recent study’s authors investigated whether biomarkers measured earlier in life can predict if someone will live to their 100th birthday [1].

35-year-long centenarian study

Previous research has found that people who become centenarians have fewer disabilities, comorbidities, and hospitalizations earlier in life. They are also characterized by better cognitive functions than people who will not reach 100 [2,3,4].

Since health seems to correlate with becoming a centenarian, these researchers asked whether a simple blood test can predict a person’s chance of reaching 100. They conducted the biggest study to date that compares biomarker profiles measured at similar ages earlier in life in centenarians and non-centenarians.

The study population consisted of 44,636 individuals from Stockholm County who underwent clinical laboratory testing between 1985 and 1996. Participants were followed up until the end of 2020.

Researchers focused specifically on people born between 1893 and 1920. Those people were between 64 and 99 years old when their first blood sample was taken for measurement. This enabled researchers to follow up with the study participants until they reached 100.

2.7% (1,224 people) of the participants reached their 100th birthday, which is representative of Stockholm’s general population in this time period.

The predictive power of blood samples

Researchers analyzed twelve blood-based biomarkers involved in inflammatory (uric acid), metabolic (total cholesterol and glucose), liver (liver enzymes and proteins), and kidney (creatinine) functions. There were also biomarker tests related to malnutrition (albumin) and anemia (iron and iron-binding capacity).

The authors compared the distribution of biomarker values between people who did and did not end up becoming centenarians. Then they studied the association between each biomarker and the possibility of becoming a centenarian. They found that except for two biomarkers (liver enzyme ALAT and albumin), all of the measured biomarkers were associated with the likelihood of becoming a centenarian.

The likelihood of becoming centenarians was higher for people who displayed increased levels of total cholesterol and iron. However, for glucose, creatinine, uric acid, liver enzymes, and total iron-binding capacity, it was the opposite: lower levels of these biomarkers are correlated with higher chances of becoming a centenarian.

The researchers also noted that blood levels of the liver enzymes ALP and LD in most of the participants, whether they were future centenarians or not, were outside of the range considered normal according to clinical guidelines.

They believe that since clinical guidelines are created for younger, healthy populations, they may not always be adequate for the elderly. This observation is even more interesting since researchers observed that higher total cholesterol levels were correlated with an increased chance of becoming a centenarian. Such observations go against clinical guidelines.

Centenarians appear generally healthier

The group that lived to become centenarians was, on average, older when the first measurement was taken. Their mean age was 79.6 years, while for non-centenarians, it was 76.7 years. Despite that, people who lived to their 100th birthday had a lower prevalence of morbidities at the time of the first measurement.

They also observed that centenarians had smaller differences in biomarker differences between the first and second measurements compared to non-centenarians.

In the centenarian group, biomarker profiles were rather homogeneous. However, the analysis identifies two profiles within the centenarian population. Researchers named them “higher nutrition” and “lower but enough nutrition.”

The “higher nutrition” profile had more similarities to the non-centenarian profiles. The differences between groups were mostly not statistically significant, with the exception of total iron-binding capacity, total cholesterol, and albumin.

Total iron-binding capacity, total cholesterol, and albumin are markers of inflammation and nutrition status [5]. Liver function and anemia can also impact their values. Researchers speculated that heterogeneity regarding total iron-binding capacity, total cholesterol, and albumin within the centenarian population might reflect nutrition but not inflammation, as other markers of inflammation, liver function, and anemia didn’t show differences within this population.

On the other hand, since the authors observed differences between centenarians and non-centenarians regarding a marker of inflammation, uric acid levels, they speculate that it is inflammation or both inflammation and nutrition that play an essential role in deciding who will live to 100.

More biomarkers could improve predictions

This research shows that from the age of 65 onwards, people who would eventually become centenarians show a difference in biomarkers.

Researchers noted that their results regarding liver and kidney function and inflammation being predictive of longevity are in agreement with previous research [6,7]. They also hypothesize that alcohol consumption might play a role in exceptional longevity. The hypothesis is based on their observation that several biomarkers that are higher in non-centenarians are alcohol-related. However, they leave this topic for future research.

The authors point out that one limitation of this study is a lack of access to all the biomarkers they had wanted to test, including ones related to immunity and inflammation. Lifestyle information, such as smoking, alcohol consumption, and physical activity, would also be informative.

Literature

[1] Murata, S., Ebeling, M., Meyer, A. C., Schmidt-Mende, K., Hammar, N., & Modig, K. (2023). Blood biomarker profiles and exceptional longevity: comparison of centenarians and non-centenarians in a 35-year follow-up of the Swedish AMORIS cohort. GeroScience, 10.1007/s11357-023-00936-w. Advance online publication.

[2] Vetrano, D. L., Grande, G., Marengoni, A., Calderón-Larrañaga, A., & Rizzuto, D. (2021). Health Trajectories in Swedish Centenarians. The journals of gerontology. Series A, Biological sciences and medical sciences, 76(1), 157–163.

[3] Engberg, H., Oksuzyan, A., Jeune, B., Vaupel, J. W., & Christensen, K. (2009). Centenarians–a useful model for healthy aging? A 29-year follow-up of hospitalizations among 40,000 Danes born in 1905. Aging cell, 8(3), 270–276.

[4] Ismail, K., Nussbaum, L., Sebastiani, P., Andersen, S., Perls, T., Barzilai, N., & Milman, S. (2016). Compression of Morbidity Is Observed Across Cohorts with Exceptional Longevity. Journal of the American Geriatrics Society, 64(8), 1583–1591.

[5] Stromberg, B. V., Davis, R. J., & Danziger, L. H. (1982). Relationship of serum transferrin to total iron binding capacity for nutritional assessment. JPEN. Journal of parenteral and enteral nutrition, 6(5), 392–394.

[6] Hirata, T., Arai, Y., Yuasa, S., Abe, Y., Takayama, M., Sasaki, T., Kunitomi, A., Inagaki, H., Endo, M., Morinaga, J., Yoshimura, K., Adachi, T., Oike, Y., Takebayashi, T., Okano, H., & Hirose, N. (2020). Associations of cardiovascular biomarkers and plasma albumin with exceptional survival to the highest ages. Nature communications, 11(1), 3820.

[7] Arai, Y., Martin-Ruiz, C. M., Takayama, M., Abe, Y., Takebayashi, T., Koyasu, S., Suematsu, M., Hirose, N., & von Zglinicki, T. (2015). Inflammation, But Not Telomere Length, Predicts Successful Ageing at Extreme Old Age: A Longitudinal Study of Semi-supercentenarians. EBioMedicine, 2(10), 1549–1558.