People who live to be a hundred and older are becoming more common. They are now the fastest-growing demographic group in the world. Researchers have been interested in understanding how long humans can live and what factors contribute to a long and healthy life for over two millennia. The pursuit of unraveling the secrets behind exceptional longevity involves understanding the complex interplay of genetic predisposition and lifestyle factors and how they interact throughout a person’s life.A new study published in GeroScience has uncovered some common biomarkers, including levels of cholesterol and glucose, in people who live past 90. Individuals aged 90 and older have been a subject of intense interest to scientists as they may provide insights into how to live longer and age in better health. Previous studies of centenarians have mostly been small-scale and focused on specific groups, excluding those living in care homes.Our study is the largest to date comparing biomarker profiles in exceptionally long-lived people and their peers who lived for shorter periods. We analyzed the biomarker profiles of individuals who lived past 100 and their shorter-lived peers, and examined the connection between the profiles and the likelihood of reaching 100.Our research involved 44,000 Swedes who underwent health assessments at ages 64-99 as part of the Amoris cohort. These participants were then tracked for up to 35 years using Swedish register data. Out of these individuals, 1,224, or 2.7%, lived to be 100 years old, with the majority (85%) being female.Twelve blood-based biomarkers related to inflammation, metabolism, liver and kidney function, as well as potential malnutrition and anemia, were included in the study. All of these biomarkers have been associated with aging or mortality in previous research.Uric acid, a waste product in the body caused by the digestion of certain foods, was the biomarker related to inflammation that was examined. We also reviewed markers linked to metabolic status and function, such as total cholesterol and glucose, as well as those related to liver function, including alanine aminotransferase (Alat), aspartate aminotransferase (Asat), albumin, gamma-glutamyl transferase (GGT), alkaline phosphatase (Alp) and lactate dehydrogenase (LD). Additionally, we looked at creatinine, which is linked to kidney function, and iron and total iron-binding capacity (TIBC), related to anemia. Finally, we examined albumin, a biomarker associated with nutrition.Our findings showed that individuals who reached 100 years of age tended to have lower levels of glucose, creatinine and uric acid from their sixties onward. Although the median values for most biomarkers did not differ significantly between centenarians and non-centenarians, centenarians rarely had very high or low values. For instance, very few centenarians had a glucose level above 6.5 or a creatinine level above 125.Both centenarians and non-centenarians had values outside the range considered normal in clinical guidelines for many of the biomarkers. This is likely because these guidelines are based on a younger and healthier population.When examining which biomarkers were associated with the likelihood of reaching 100, we found that all but two (Alat and albumin) of the 12 biomarkers showed a connection to reaching 100, even after considering age, sex, and disease burden. Individuals in the lowest out of five groups for levels of total cholesterol and iron had a lower chance of reaching 100 compared to those with higher levels. Additionally, people with higher levels of glucose, creatinine, uric acid and markers for liver function also had a reduced chance of becoming a centenarian.The differences in absolute terms were relatively small for some biomarkers, while for others they were somewhat more noticeable. For example, the absolute difference for uric acid was 2.5 percentage points. This means that individuals with the lowest uric acid levels had a 4% chance of reaching 100, whereas those with the highest levels only had a 1.5% chance.Even though the differences we observed were generally small, they suggest a potential link between metabolic health, nutrition, and exceptional longevity. Although the study does not draw conclusions about which lifestyle factors or genes are responsible for the biomarker values, it is reasonable to assume that factors such as nutrition and alcohol intake play a role. Monitoring kidney and liver values, as well as glucose and uric acid as individuals age, is likely a good idea. However, chance likely plays a role in reaching an exceptional age at some point. The observation of differences in biomarkers long before death suggests that genes and lifestyle may also play a part. 
Karin Modig, Associate Professor, Epidemiology, Karolinska InstitutetThis article is republished from The Conversation under a Creative Commons license. Read the original article.An earlier version of this article was published in October 2023.
