Supercentenarians Have Inflammatory Scores Similar to Those of Younger Adults

One of the many reasons to think that chronic inflammation is an important aspect of degenerative aging is that extremely old individuals, those who have outlived more than 99% of their birth cohort, tend to exhibit levels of inflammation that are similar to those of younger adults. A number of studies of centenarians (100 years and older), semi-supercentenarians (105 years and older) and supercentenarians (110 years and older) have noted unusually low levels of inflammatory markers, typically lower than the inflammation normally seen in later life from 60 to 100 in the general population.

This is not to say that being older than 100 is a walk in the park, as matters presently stand. These individuals approach a 50% yearly mortality rate, are frail, and suffer many of the usual issues of old age. Calling them relatively healthy might be accurate, but it isn’t by any means a desirable state of being when compared to healthy adult life at younger ages. Returning to the point on inflammation, today’s open access paper is one of a number to demonstrate that extremely old survivors past the age of 100 exhibit lower inflammatory signaling than the average individual in the few decades approaching 100. Near everyone with a greater burden of chronic inflammation than these survivors dies before reaching 100 years of life.

Immune-Inflammatory Response in Lifespan - What Role Does It Play in Extreme Longevity? A Sicilian Semi- and Supercentenarians Study

Among Long-Lived Individuals (LLIs, ≥90 years), centenarians (≥100 years), including semi-supercentenarians (105-109 years) and supercentenarians (≥110 years), are a focus of extensive research. Most of them are resistant to or manage age-related diseases such as cancer, diabetes, cardiovascular diseases, and stroke. Thus, they are categorized as survivors, escapers, or delayers. However, it is important to recognize that the growing number of centenarians is due to advancements in hygiene and sanitation, as well as healthier lifestyles. Consequently, contemporary and future centenarians are likely to be less selectively unique than those from previous decades. Semi- and supercentenarians represent a uniquely selective group. They have endured significant adversities, including two World Wars, the Spanish flu, and the COVID-19 pandemics. Therefore, it is plausible to infer that their immune systems exhibit remarkable traits that can provide insights into the mechanisms influencing the achievement of such extreme longevity.

Age-related dysregulation of immune-inflammatory responses (IMFLAM) has indeed been recognized for several years. In 1980, researchers conceptualized the term immunosenescence, while in 2000, others highlighted that aging is marked by a progressive increase in pro-inflammatory status, known as inflammaging. This persistent systemic inflammation is associated with cellular senescence, immune decline, organ dysfunction, and age-related diseases. Simultaneously, chronic inflammation accelerates immunosenescence, resulting in reduced immune capacity and a weakened ability to clear senescent cells and inflammatory agents, thus perpetuating a detrimental cycle.

This paper analyzes the inflammatory scores - INFLA-score and Systemic Inflammation Response Index (SIRI) - and Aging-Related Immune Phenotype (ARIP) indicators calculated from the dataset of the DESIGN project, including 249 participants aged 19 to 111 years, aiming to understand the IMFLAM role in achieving longevity. Statistical analyses were performed to explore the correlations between these parameters and age. Both INFLA-score and SIRI showed a significant increase with age. However, no statistical differences were found when comparing the values of semi- and supercentenarians to other age groups, which are similar to adults and lower than younger centenarians. Regarding ARIP values, it is noteworthy that when comparing the CD8+ Naïve/Effector scores between groups, no significant differences were observed between the semi- and supercentenarian group and the other groups. These results support the idea that the control of IMFLAM response can promote extreme longevity.

4 Likes

Did they even use the proper measurements of inflammation (like interleukins and TNF-alpha?)

fwiw NU’s Sharena Kelley (Shaking Sensor Continuously Monitors Inflammation | News | Northwestern Engineering ) has people who are continuously measuring inflammation

the title is a misnomer, only SOME inflammatory scores are similar. what about interferons? and endogenous inflammation (not the kind driven by WBCs)

1 Like

2.3. Inflammatory Scores: INFLA-Score and SIRI

The INFLA-score was calculated by creating deciles for leukocyte (WBC) count, neutrophil to lymphocyte ratio (NLR) values, platelet count, and C reactive protein (CRP). Each biomarker’s data were split into ten groups according to value, with the first decile representing the lowest values, the second decile representing slightly higher values, continuing in this way until the tenth decile, which included the highest values. These biomarker deciles were assigned scores ranging from low values (−4 to −1) to high values (+1 to +4), while intermediate values were assigned a score of 0. The INFLA-score is obtained by summing the scores of the four components, resulting in a possible range from −16 to +16 [15]. The SIRI was calculated according to Qi et al. (neutrophils x monocytes/lymphocytes) [16]. Leukocyte and inflammatory values were obtained as previously described [11,18].

2.4. Immunological Scores: ARIP

The ARIP includes the CD4/CD8 ratio, CD4+ and CD8+ T Naïve cells, and the T Naïve (TN)/TM (TM = T Central Memory (TCM) + T Effector Memory (TEM) + Terminally Differentiated Effector Memory (TEMRA)) for both CD4+ and CD8+ T cells [17], calculated on a subcohort of 54 individuals [11].

2.5. Statistics

The correlation between the various parameters and age was examined using simple linear regression analysis. A one-way ANOVA test was used to compare data between the different age groups, applying Tukey’s correction. For all statistical analyses, only p-values ≤ 0.05 were considered significant.

4 Likes