Biomarkers that can predict a long life

Chris Street edits in bold.

My Action: Test for CRP, IL-6, fibrinogen, EPI and NE etc

What biochemicals can predict how long I will live?

Full Review:
"Combinations of biomarkers predictive of laterlife mortality" in PNAS September 19th 2006 vol. 103 no. 38, Gruenewald et al. Download the full article pdf (save $10) - Recommended.

13 biomarkers, reflecting activity in several biological systems predict death or ill health in older adults.

Neuroendocrine stress hormones
Nerve cells (Neuroendocrine glands) produce four hormones that are released under conditions of stress.

• Adrenaline
• aka epinephrine (EPI)
  
• plays a role under conditions of stress and anger
• Noraadrenaline
• aka norepinephrine (NE)
• is released by a stressful event.
• cortisol
• is involved in response to stress; increases blood pressure, blood sugar levels, and suppresses the immune system.
• dehydroepiandrosterone (DHEA)
• a natural steroid hormone produced from cholesterol. DHEA is the precursor of androstenedione, testosterone and estrogen. It is the most abundant hormone in the human body.

Immune activity

• C-reactive protein (CRP)
  
• a marker of inflammation. High levels indicate risk of developing fatty deposits on inner walls of arteries which can lead to heart attacks.
• Fibrinogen
• Fibrin made from fibrinogen is a protein involved in clotting of blood
• Interleukin 6 (IL-6)
  
• is a cytokine secreted by T cells and macrophages to stimulate immune response to trauma, especially burns or other tissue damage leading to inflammation.
• Albumin
• most abundant protein in human blood plasma. High levels is a sign of severe dehydration. Low levels can be caused by malnutrition, malabsorption, liver disease, etc.

Cardiovascular functioning

• Systolic (SBP) and Diastolic blood pressure (DBP)
• The systolic pressure is the peak pressure in the arteries during the cardiac cycle
• the diastolic pressure is the lowest pressure (at the resting phase of the cardiac cycle).

Metabolic activity

• High-density lipoprotein (HDL) cholesterol

• HDL can remove cholesterol from atheroma within arteries, and transport it back to the liver for excretion or re-utilization.
  

• HDL-bound cholesterol is called "good cholesterol" - protects against cardiovascular diseases.
  

• Low HDL cholesterol levels [less than 40 mg/dL] increase the risk for heart disease.

• total cholesterol to HDL cholesterol ratio
• Glycosylated hemoglobin (HbA1c)
• a form of hemoglobin used primarily to identify the plasma glucose concentration
• formed by hemoglobin's normal exposure to high plasma levels of glucose
• found in retinopathy in diabetes mellitus.

Aims:-

• (i) identify combinations of biomarkers and their zones of values associated with high levels of mortality risk in older men and women
  
• (ii) examine whether biomarkers differ between men and women
  
• (iii) introduce prediction rules that are based on conjunctions of biomarker conditions.
  

A secondary aim is to present recursive partitioning (RP) that allows for identification of combinations of biomarkers and their value zones.

Throughout, the focus is on identifying subclinical levels of biomarkers that characterize high-risk (HR) conditions, because such knowledge has the potential to contribute to preventive interventions that might prolong life beyond what is expected on the basis of current clinical risk criteria.

Biomarkers were selected for use in analyses if the biomarker was:-

• a primary mediator of a biological regulatory system responsive to internal or external challenges (e.g., sympathetic nervous system hormones and inflammatory cytokines, such as IL-6)
  
• the biomarker was known to exhibit change in response to interaction with a primary mediator (e.g., CRP production in response to IL-6).
  
• The remaining measures were selected to represent secondary outcomes of these mediating processes.
  

For example, a combination of high levels of NE, CRP, and EPI led to a subgroup of 30 male participants (terminal node 12 in Fig. 1) with a mortality rate of 93.3% within the group. A second group of male participants (terminal node 9) with a high mortality rate (83.3%) is characterized by a combination of biomarkers that includes NE levels in a moderate range, high levels of IL-6, and low levels of HDL cholesterol.

Results
Each biomarker for male and female participants are presented in Table 1.



Recursive Partitioning Forests and Mortality Prediction.




Discussion
In men, markers of the endocrine and immune systems were commonly represented in HR mortality pathways, with a lesser role for indicators of the cardiovascular and metabolic systems. Fewer HR pathways were identified in women, but a range of biomarkers was present, including blood pressure, inflammatory markers, DHEA, and HbA1c.

With a focus on prevention, it may be useful to include assays on biomarkers such as CRP, IL-6, fibrinogen, EPI, and NE as part of a standard physical examination.

A prediction rule for mortality, using a single tree, was specified as follows: predict dead within 12 years of baseline if the individual has biomarker conditions as specified by a pathway into a terminal node with mortality rate 70% (males) or 60% (females).