14 Biomarkers Predict Death: A Closer Look at Mortality Risk

Researchers have identified 14 blood biomarkers that predict mortality risk with significant accuracy. These markers reflect various physiological processes, offering insights into overall health and lifespan. Understanding them could enhance early interventions and personalized medical strategies.

Advancements in science now allow for a detailed assessment of how biological systems influence longevity. This article examines key categories of these biomarkers and their role in predicting health outcomes.

Metabolic Markers

Metabolic markers reveal the body’s ability to regulate energy production, nutrient utilization, and biochemical balance. Among the 14 mortality-linked biomarkers, several relate to metabolic function, reflecting how efficiently the body processes lipids, glucose, and other essential compounds. Disruptions in these markers often signal an increased risk of chronic disease and reduced lifespan.

One of the most predictive metabolic indicators is glucose regulation, particularly fasting blood glucose and glycated hemoglobin (HbA1c). Elevated levels suggest impaired insulin sensitivity, a hallmark of type 2 diabetes and metabolic syndrome. A 2020 study in The Lancet Diabetes & Endocrinology found that individuals with persistently high HbA1c levels had a significantly higher risk of all-cause mortality, even without diagnosed diabetes. This underscores the importance of maintaining stable blood sugar levels through diet, exercise, and medication when necessary.

Lipid metabolism also plays a key role in longevity, with abnormal cholesterol and triglyceride levels predicting cardiovascular disease. Low-density lipoprotein (LDL) cholesterol, or “bad cholesterol,” contributes to arterial plaque formation, while high-density lipoprotein (HDL) cholesterol, or “good cholesterol,” helps remove excess lipids from circulation. A meta-analysis in Circulation found that individuals with an LDL-to-HDL ratio above 3.5 faced a markedly higher risk of premature death, reinforcing the need for lipid management through lifestyle changes and, in some cases, statin therapy.

Amino acid metabolism has also emerged as a mortality predictor. Branched-chain amino acids (BCAAs)—leucine, isoleucine, and valine—are essential for muscle maintenance, yet excessive circulating levels have been linked to insulin resistance and metabolic dysfunction. A 2019 study in Nature Medicine found that elevated BCAA concentrations were associated with a 30% increased mortality risk over a decade, particularly in individuals with obesity. While amino acids are necessary for physiological function, imbalances can contribute to long-term health decline.

Inflammatory Markers

Chronic inflammation is a strong predictor of mortality, with persistent elevations in specific biomarkers correlating with increased risks of age-related diseases. These markers indicate underlying pathological processes, including vascular damage, metabolic disturbances, and tissue degeneration, all of which contribute to reduced lifespan.

C-reactive protein (CRP), a liver-derived protein, rises in response to systemic inflammation. High-sensitivity CRP (hs-CRP) testing detects low-grade chronic inflammation linked to cardiovascular disease, cancer, and neurodegenerative conditions. A 2021 meta-analysis in The BMJ found that individuals with hs-CRP levels above 3 mg/L had a 44% higher risk of mortality compared to those below 1 mg/L. Elevated CRP is often associated with obesity, sedentary behavior, and poor diet, making lifestyle changes a primary strategy for reducing inflammation.

Interleukin-6 (IL-6), a pro-inflammatory cytokine, also predicts mortality risk. While IL-6 plays a role in immune signaling, sustained elevations contribute to muscle wasting, insulin resistance, and vascular dysfunction. A 2020 study in Nature Aging found that older adults with persistently high IL-6 levels had a 50% greater likelihood of death over a decade. The study emphasized IL-6’s role in age-related frailty, suggesting that targeting inflammation could improve longevity.

Tumor necrosis factor-alpha (TNF-α), another inflammatory mediator, is linked to increased mortality, particularly in individuals with chronic diseases. TNF-α promotes cellular apoptosis and oxidative stress, exacerbating conditions such as atherosclerosis and neurodegeneration. Research in The Journal of Clinical Endocrinology & Metabolism found that elevated TNF-α levels were strongly associated with all-cause mortality in type 2 diabetes patients, independent of glycemic control. This suggests inflammation contributes to disease progression beyond metabolic dysfunction alone.

Organ Function Indicators

Organ efficiency significantly impacts longevity, with biomarkers reflecting kidney, liver, and cardiovascular health offering valuable mortality insights. Even subtle declines in organ function can be detected through biochemical markers before clinical symptoms appear, making them essential for predicting long-term health outcomes.

Kidney function, assessed through estimated glomerular filtration rate (eGFR) and serum creatinine levels, is a strong survival predictor. Declining eGFR indicates reduced filtration capacity, leading to toxin accumulation and systemic complications. A longitudinal analysis in The New England Journal of Medicine found that individuals with eGFR below 60 mL/min/1.73 m² had a twofold increase in all-cause mortality. Even mild impairments were linked to higher cardiovascular risk, highlighting the connection between renal health and overall survival.

Liver function markers, including albumin and bilirubin, also provide prognostic value. Albumin, a protein synthesized by the liver, is essential for maintaining oncotic pressure and transporting hormones and nutrients. Low serum albumin often indicates chronic disease, malnutrition, or hepatic dysfunction. A study in Hepatology found that individuals with albumin below 3.5 g/dL had significantly higher mortality rates. Bilirubin, commonly associated with liver clearance, has a complex relationship with longevity. While excessively high levels indicate hepatic impairment, mildly elevated bilirubin within the normal range has been linked to reduced oxidative stress and lower cardiovascular risk.

Cardiac biomarkers further refine mortality risk assessment. Elevated levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) and troponins signal cardiac stress and myocardial injury. NT-proBNP, released in response to ventricular strain, is widely used to assess heart failure severity. A cohort study in Circulation found that individuals in the highest NT-proBNP quartile had a threefold increase in mortality compared to those in the lowest quartile. Similarly, troponins, which indicate myocardial cell damage, have been detected in asymptomatic individuals with subclinical heart disease, suggesting they serve as an early warning sign for future cardiac events.

Hormonal and Nutritional Markers

Hormonal balance and nutritional status influence longevity, affecting metabolic efficiency, tissue maintenance, and physiological resilience. Among the mortality-linked biomarkers, several reflect endocrine function and nutrient levels, offering insight into long-term health.

Testosterone and dehydroepiandrosterone sulfate (DHEA-S) are key hormonal indicators, particularly in men. Low testosterone is associated with frailty, muscle loss, and cardiovascular disease, while diminished DHEA-S, a precursor to androgens and estrogens, has been linked to higher mortality. Research in The Journal of Clinical Endocrinology & Metabolism found that men in the lowest DHEA-S quartile had a 34% greater risk of death over a decade. These findings highlight the role of sex hormones in maintaining physiological resilience.

Nutritional biomarkers, including vitamin D and albumin, further refine mortality predictions. Vitamin D, beyond its role in bone health, supports cellular repair and metabolic regulation. Studies show that individuals with serum 25-hydroxyvitamin D levels below 20 ng/mL face higher risks of cardiovascular events and overall mortality. Meanwhile, albumin, a marker of protein status and systemic health, declines with chronic disease and malnutrition, making it a reliable indicator of survival prospects.

Interplay Among Multiple Markers

While individual biomarkers offer valuable mortality insights, their predictive power increases when analyzed collectively. Physiological systems do not function in isolation, and disruptions in one area can trigger cascading effects across multiple biological pathways. Mortality risk is best understood through a systems-based approach rather than focusing on single biomarkers.

For example, elevated C-reactive protein (CRP) alone indicates systemic inflammation, but when combined with high fasting glucose and low albumin, it suggests broader metabolic dysfunction that increases susceptibility to chronic disease. Similarly, individuals with both reduced kidney filtration and elevated N-terminal pro-brain natriuretic peptide (NT-proBNP) levels face a significantly higher risk of cardiovascular death than those with abnormalities in just one of these markers. A study in JAMA Internal Medicine found that a composite risk model incorporating multiple biomarkers improved mortality prediction by 30% compared to conventional risk factors alone.

In clinical practice, biomarker panels enable personalized interventions. Physicians can identify at-risk individuals earlier and implement targeted lifestyle or medical therapies before overt disease develops. Advances in machine learning are further refining predictive models, enhancing early detection strategies, and improving individualized treatment plans. As precision medicine evolves, analyzing multiple physiological markers will enhance proactive health strategies and disease prevention.