Understanding Blood Biomarkers for Longevity
Longevity science has identified specific blood biomarkers that consistently predict healthspan, lifespan, and disease risk decades before symptoms appear. These biomarkers, studied extensively in centenarians and long-lived populations, provide actionable targets for extending both the length and quality of life.
Unlike standard blood testing focused on disease diagnosis, longevity biomarker tracking enables proactive optimization—identifying and correcting metabolic dysfunction, inflammation, hormonal decline, and nutrient deficiencies that accelerate aging. Research published in Nutrients (2022) analyzing biomarkers in exceptionally long-lived individuals reveals consistent patterns: excellent glucose control, low inflammation, optimal lipid profiles, preserved organ function, and maintained hormonal balance.
This guide examines the most important blood biomarkers for longevity, optimal ranges based on research rather than population averages, mechanisms linking each biomarker to aging, and evidence-based strategies for optimization. Understanding and tracking these markers empowers informed decisions about diet, lifestyle, supplementation, and medical interventions to maximize healthspan.
Metabolic Health Biomarkers
HbA1c: Glycemic Control and Longevity
Hemoglobin A1c (HbA1c) measures average blood glucose over the preceding 2-3 months by quantifying glucose-bound hemoglobin. This single biomarker powerfully predicts cardiovascular disease, dementia, cancer, kidney disease, and all-cause mortality—even at levels considered "normal" by conventional standards.
Research on centenarians consistently demonstrates HbA1c levels below 5.5% (36 mmol/mol) throughout life. While diabetes is diagnosed at HbA1c ≥6.5% (48 mmol/mol) and prediabetes at 5.7-6.4% (39-46 mmol/mol), optimal levels for longevity are significantly lower: 4.8-5.4% (29-36 mmol/mol), with the ideal target being approximately 5.0-5.2% (31-33 mmol/mol).
Elevated HbA1c, even within "normal" ranges, indicates chronic hyperglycemia that damages blood vessels through glycation—the process where excess glucose binds to proteins, creating advanced glycation end products (AGEs) that impair tissue function. This vascular damage accelerates atherosclerosis, impairs cognitive function, damages kidneys, and promotes inflammation throughout the body.
Studies show that each 1% increase in HbA1c above optimal levels increases cardiovascular mortality risk by approximately 20-30%. An HbA1c of 6.0% (42 mmol/mol)—still below the diabetic threshold—carries significantly higher mortality risk than 5.0% (31 mmol/mol). This dose-response relationship emphasizes the importance of maintaining excellent glucose control for longevity.
Optimization strategies: Reducing HbA1c requires addressing insulin resistance through carbohydrate restriction (particularly refined carbs and sugars), time-restricted eating or intermittent fasting, regular exercise (especially resistance training and high-intensity interval training), adequate sleep, stress management, weight loss if overweight, and potentially supplements like berberine, alpha-lipoic acid, and chromium. Continuous glucose monitoring (CGM) provides real-time feedback for dietary optimization.
Fasting Insulin: The Earliest Metabolic Warning
Fasting insulin is arguably the most important yet most under-tested longevity biomarker. Elevated insulin—hyperinsulinemia—is the earliest detectable sign of metabolic dysfunction, appearing years or even decades before blood glucose or HbA1c rise into abnormal ranges.
Optimal fasting insulin for longevity is ≤5 μIU/mL, with ideal levels being 2-5 μIU/mL. Standard laboratory reference ranges extend to 25 μIU/mL or higher, but research shows that fasting insulin above 8-10 μIU/mL indicates insulin resistance and significantly increases cardiovascular disease risk, independent of glucose levels.
Hyperinsulinemia drives multiple aging processes: it promotes fat storage (particularly visceral fat), increases inflammation, elevates blood pressure, promotes cellular proliferation (potentially increasing cancer risk), impairs autophagy (cellular cleanup), and accelerates vascular damage. Chronically elevated insulin is a primary driver of metabolic syndrome—the constellation of insulin resistance, abdominal obesity, hypertension, and dyslipidemia that dramatically increases disease risk.
Prospective cohort studies demonstrate that elevated fasting insulin predicts type 2 diabetes development 10-20 years in advance and independently predicts cardiovascular events and mortality. The Framingham Heart Study showed that fasting insulin in the highest quartile (>10 μIU/mL) doubled cardiovascular risk compared to the lowest quartile, even after adjusting for other risk factors.
Optimization strategies: Lowering insulin requires the same interventions that improve insulin sensitivity: low-glycemic carbohydrate intake, elimination of refined sugars and processed foods, adequate protein and healthy fats, time-restricted eating (allowing 12-16 hour fasting windows), regular exercise (especially resistance training to build muscle mass which acts as a glucose sink), weight loss if overweight, adequate sleep (sleep deprivation dramatically increases insulin resistance), and stress management. Supplements like berberine, inositol, and magnesium may support insulin sensitivity.
Triglycerides and Metabolic Health
Fasting triglycerides reflect carbohydrate metabolism and are closely linked to insulin resistance. Optimal triglycerides for longevity are <100 mg/dL (1.13 mmol/L), with ideal levels being 50-80 mg/dL (0.56-0.90 mmol/L). Standard reference ranges extend to 150 mg/dL, but levels above 100 mg/dL indicate metabolic dysfunction.
The triglyceride-to-HDL ratio (calculated by dividing triglycerides by HDL cholesterol, both in mg/dL) is an excellent insulin resistance marker. Optimal ratio is <2, with ideal being <1. Ratios above 3 indicate significant insulin resistance and increased cardiovascular risk. This ratio often predicts metabolic problems better than any single lipid measurement.
Elevated triglycerides result primarily from excess carbohydrate intake—particularly fructose and refined carbohydrates—being converted to fat in the liver (de novo lipogenesis). High triglycerides increase cardiovascular disease risk through multiple mechanisms: production of small dense LDL particles (highly atherogenic), inflammation, impaired HDL function, and contribution to fatty liver disease.
Optimization strategies: Triglycerides respond rapidly to dietary intervention: reducing sugar and refined carbohydrates, limiting alcohol (metabolized similarly to fructose), increasing omega-3 fatty acids from fatty fish or supplements, weight loss, and regular exercise. Many people see 50% reductions in triglycerides within weeks of eliminating added sugars and refined carbs. High-dose omega-3 supplementation (2-4 grams EPA+DHA daily) can lower triglycerides by 20-40%.
Cardiovascular Risk Biomarkers
ApoB: The Superior Lipid Marker
Apolipoprotein B (ApoB) is the primary protein component of all atherogenic lipid particles: LDL, VLDL, IDL, and Lp(a). Crucially, each particle contains exactly one ApoB molecule, making ApoB a direct measure of the number of atherogenic particles—far superior to LDL cholesterol (LDL-C), which measures cholesterol content rather than particle count.
Optimal ApoB for longevity is <90 mg/dL (0.90 g/L) for primary prevention in healthy individuals, with ideal levels being 60-80 mg/dL. For those with existing cardiovascular disease or very high risk, target <80 mg/dL or even <70 mg/dL. The European Atherosclerosis Society consensus statement identifies ApoB as the preferred marker for cardiovascular risk assessment.
Why does ApoB matter more than LDL-C? LDL particles vary in size and cholesterol content. Small, dense LDL particles carry less cholesterol but are more atherogenic than large, fluffy LDL particles. Two individuals with identical LDL-C levels may have dramatically different particle numbers—and therefore different cardiovascular risk. ApoB captures this discordance by counting particles directly.
Research demonstrates that ApoB is causal in atherosclerosis: each ApoB-containing particle that enters the arterial wall contributes to plaque formation. Lifelong exposure to elevated ApoB leads to progressive atherosclerosis, while maintaining low ApoB throughout life—as seen in centenarians—prevents arterial disease. Mendelian randomization studies confirm causality: genetic variants that lower ApoB reduce cardiovascular events proportional to the degree of ApoB reduction.
ApoB also reflects metabolic health: elevated ApoB often accompanies insulin resistance, high triglycerides, and low HDL—the pattern seen in metabolic syndrome. Improving insulin sensitivity typically lowers ApoB.
Optimization strategies: Reducing ApoB requires addressing both LDL particle production and clearance. Effective interventions include: saturated fat reduction (particularly from processed and fried foods), trans fat elimination, increased soluble fiber intake (5-10 grams daily from oats, psyllium, legumes), plant sterols/stanols (2 grams daily), weight loss if overweight, regular exercise, and ensuring adequate thyroid function. Statins remain the most effective pharmaceutical intervention when lifestyle changes are insufficient. Ezetimibe, bempedoic acid, and PCSK9 inhibitors provide additional options for those requiring aggressive lipid lowering.
Lipoprotein(a): The Genetic Risk Factor
Lipoprotein(a) or Lp(a) is an LDL-like particle attached to an apolipoprotein(a) molecule. Lp(a) is almost entirely genetically determined—diet and lifestyle have minimal impact on levels. Approximately 20% of the population has elevated Lp(a) >50 mg/dL, which significantly increases cardiovascular disease risk independent of other risk factors.
Optimal Lp(a) is <30 mg/dL (75 nmol/L), with ideal being <10 mg/dL. Levels above 50 mg/dL increase cardiovascular risk approximately 1.5-2 times; levels above 125 mg/dL may triple risk. Lp(a) is particularly atherogenic because it carries oxidized phospholipids that promote inflammation and plaque formation, plus the apo(a) component has pro-thrombotic properties.
Everyone should test Lp(a) at least once, as levels remain stable throughout life. If elevated, more aggressive management of other cardiovascular risk factors becomes essential: maintaining very low ApoB (<70 mg/dL), optimal blood pressure, excellent glycemic control, and lifestyle optimization. Emerging therapies specifically targeting Lp(a) are in development.
Management strategies: Since Lp(a) is genetically determined, focus on aggressive reduction of modifiable risk factors: achieving very low ApoB levels through statins, ezetimibe, or PCSK9 inhibitors; maintaining optimal blood pressure; excellent glucose control; aspirin therapy (if appropriate); maximizing lifestyle factors (exercise, diet, stress management, sleep). High-dose niacin can lower Lp(a) by 20-30% but has side effects and uncertain benefit. Newer therapies including antisense oligonucleotides targeting Lp(a) production show promise in clinical trials.
Inflammation and Longevity
High-Sensitivity C-Reactive Protein
High-sensitivity C-Reactive Protein (hs-CRP) measures systemic inflammation—a fundamental driver of aging and age-related disease. The concept of "inflammaging" describes how chronic low-grade inflammation accelerates cellular aging, impairs tissue repair, promotes atherosclerosis, increases cancer risk, and contributes to neurodegeneration.
Optimal hs-CRP for longevity is <1.0 mg/L, with ideal levels being <0.5 mg/L. Standard cardiovascular risk stratification defines: <1 mg/L = low risk, 1-3 mg/L = moderate risk, >3 mg/L = high risk. However, for longevity optimization, maintaining levels well below 1 mg/L is ideal. Centenarian studies consistently show hs-CRP levels <1 mg/L despite advanced age.
The landmark Emerging Risk Factors Collaboration meta-analysis of over 160,000 individuals demonstrated that elevated hs-CRP independently predicts cardiovascular events, cancer mortality, and all-cause mortality. Each doubling of hs-CRP increases cardiovascular risk by approximately 25%, even after adjusting for traditional risk factors like cholesterol and blood pressure.
Chronic inflammation damages the cardiovascular system by promoting endothelial dysfunction, oxidizing LDL particles (making them more atherogenic), destabilizing arterial plaques (increasing rupture risk), and activating the coagulation system. Beyond cardiovascular disease, inflammation drives metabolic dysfunction (inflammation impairs insulin signaling), neurodegenerative disease (neuroinflammation damages brain tissue), cancer (inflammatory environment promotes tumor growth), and accelerates cellular aging through oxidative stress and telomere shortening.
Optimization strategies: Reducing hs-CRP requires addressing inflammation sources: weight loss if overweight (adipose tissue produces inflammatory cytokines), regular exercise (particularly moderate intensity—though intense exercise can temporarily elevate hs-CRP), anti-inflammatory diet rich in omega-3 fatty acids, colorful vegetables, berries, and polyphenols while minimizing processed foods, refined carbohydrates, and trans fats. Adequate sleep (poor sleep elevates inflammation), stress management (chronic stress drives inflammation), dental health (periodontal disease increases systemic inflammation), and addressing chronic infections. Omega-3 supplementation (2-4 grams EPA+DHA daily), curcumin, and other anti-inflammatory compounds may help reduce hs-CRP.
White Blood Cell Count
White blood cell (WBC) count, even within the normal range, correlates with inflammation and mortality risk. Optimal WBC count for longevity is in the lower half of the reference range: 4.0-6.0 × 10⁹/L, with ideal being approximately 4.5-5.5 × 10⁹/L. Reference ranges typically extend to 11.0 × 10⁹/L, but levels consistently above 7.0 × 10⁹/L indicate elevated inflammation and increased cardiovascular risk.
Elevated WBC count within the "normal" range associates with increased risk of cardiovascular disease, diabetes, cancer, and all-cause mortality in multiple cohort studies. This relationship reflects chronic low-grade inflammation and immune activation. Conversely, individuals with exceptional longevity tend to have WBC counts in the lower normal range.
The differential WBC count (percentages of neutrophils, lymphocytes, monocytes, eosinophils, and basophils) provides additional information. The neutrophil-to-lymphocyte ratio (NLR) serves as an inflammatory marker: optimal NLR is <2.0, with levels above 3.0 indicating significant inflammation and immune activation associated with increased mortality risk.
Methylation and Vascular Health
Homocysteine: Methylation and Cardiovascular Risk
Homocysteine is an amino acid produced during methionine metabolism. Elevated homocysteine indicates impaired methylation—a crucial biochemical process involving over 200 reactions essential for DNA repair, neurotransmitter production, detoxification, and gene expression regulation. High homocysteine also directly damages blood vessels, promoting atherosclerosis, stroke, and venous thrombosis.
Optimal homocysteine for longevity is <8 μmol/L, with ideal levels being 5-7 μmol/L. Standard reference ranges extend to 15 μmol/L, but cardiovascular disease risk increases progressively above 10 μmol/L. Each 5 μmol/L increase in homocysteine increases stroke risk by approximately 20% and cardiovascular disease risk by 10-15%.
Elevated homocysteine most commonly results from B-vitamin deficiencies—particularly vitamin B12, folate (B9), and vitamin B6—which serve as cofactors for enzymes that metabolize homocysteine. Genetic variants in the MTHFR gene (affecting approximately 40% of the population) impair folate metabolism and increase homocysteine levels, especially with inadequate folate intake. Kidney disease also elevates homocysteine as renal clearance declines.
Beyond cardiovascular disease, elevated homocysteine associates with cognitive decline and dementia. Studies show that individuals with high homocysteine experience accelerated brain atrophy and greater cognitive decline. B-vitamin supplementation that lowers homocysteine can slow brain atrophy and cognitive decline in older adults, particularly those with elevated baseline homocysteine.
Optimization strategies: Lowering homocysteine is straightforward and highly effective: supplementation with methylated B vitamins (methylcobalamin or hydroxocobalamin for B12, methylfolate or folinic acid for folate, and pyridoxal-5-phosphate for B6). Typical effective doses are: B12 500-1000 mcg daily, methylfolate 400-800 mcg daily, and B6 25-50 mg daily. Dietary sources include leafy green vegetables (folate), animal products (B12), and legumes (folate and B6). Most people see significant homocysteine reductions (20-40%) within 8-12 weeks of supplementation. For those with MTHFR variants, methylated forms of B vitamins are particularly important.
Essential Nutrient Biomarkers
Vitamin D: Immune Function and Longevity
Vitamin D functions more as a hormone than a vitamin, with receptors in virtually every tissue. Vitamin D regulates immune function, bone health, cardiovascular health, insulin sensitivity, mood, and gene expression. Deficiency is extraordinarily common—over 40% of UK adults have insufficient levels, with higher rates in winter months and among those with darker skin or limited sun exposure.
Optimal 25-hydroxyvitamin D [25(OH)D] levels for longevity are 100-150 nmol/L (40-60 ng/mL), significantly higher than NHS "sufficiency" threshold of 50 nmol/L (20 ng/mL). Research consistently demonstrates that levels above 75 nmol/L (30 ng/mL) reduce risk of respiratory infections, autoimmune disease, cardiovascular events, cancer, and all-cause mortality compared to deficient levels. Many longevity experts target 100-125 nmol/L (40-50 ng/mL) for optimal health.
Vitamin D supports innate and adaptive immunity: it enhances antimicrobial peptide production, modulates inflammatory responses, and reduces autoimmune disease risk. Studies show that vitamin D supplementation reduces acute respiratory infections by 10-50%, with greatest benefit in those with deficiency. Low vitamin D levels associate with increased risk of influenza, pneumonia, and severe COVID-19 outcomes.
For cardiovascular health, vitamin D deficiency increases hypertension, atherosclerosis, and heart failure risk. Observational studies show strong inverse correlations between vitamin D levels and cardiovascular disease and mortality. For metabolic health, adequate vitamin D improves insulin sensitivity and reduces diabetes risk. For cancer prevention, higher vitamin D levels associate with reduced risk of colorectal, breast, and other cancers.
Optimization strategies: Most UK residents require supplementation to achieve optimal levels: 2000-4000 IU (50-100 mcg) daily for maintenance, with higher doses (5000-10,000 IU) for correcting deficiency. Individual requirements vary based on genetics, body weight (obese individuals require higher doses), sun exposure, and skin pigmentation. Vitamin D is fat-soluble, so taking with a meal containing fat improves absorption. Test levels 3-4 months after starting supplementation to verify adequacy. Vitamin D3 (cholecalciferol) is preferred over D2 (ergocalciferol). Safe upper limits are approximately 150-200 nmol/L (60-80 ng/mL); toxicity is rare below these levels.
Vitamin B12 and Folate: Methylation and Cognitive Health
Vitamin B12 (cobalamin) is essential for DNA synthesis, red blood cell formation, neurological function, and homocysteine metabolism. Deficiency is common, particularly in older adults (reduced stomach acid impairs absorption), vegetarians/vegans (B12 is found almost exclusively in animal products), and those taking metformin or proton pump inhibitors (PPIs) which impair absorption.
Optimal serum B12 for longevity is >400 pmol/L (>550 pg/mL), with ideal levels being 500-900 pmol/L (680-1220 pg/mL). Standard reference ranges extend down to 150-200 pmol/L, but neurological damage can occur at levels below 300 pmol/L. For more accurate functional B12 assessment, test methylmalonic acid (MMA)—elevated MMA (>270 nmol/L) indicates functional B12 deficiency even when serum B12 appears normal.
B12 deficiency causes fatigue, cognitive impairment, depression, peripheral neuropathy (nerve damage causing numbness and tingling), and macrocytic anemia. Neurological damage from B12 deficiency can be permanent if prolonged, emphasizing the importance of maintaining optimal levels. Adequate B12 is critical for maintaining low homocysteine, protecting against cognitive decline and cardiovascular disease.
Folate (vitamin B9) works synergistically with B12 in homocysteine metabolism and DNA synthesis. Optimal serum folate is >20 nmol/L (>9 ng/mL), with ideal levels being 25-50 nmol/L. Red blood cell (RBC) folate provides a better measure of long-term folate status: optimal RBC folate is >900 nmol/L.
Optimization strategies: For B12, supplementation with 500-1000 mcg daily of methylcobalamin or hydroxocobalamin effectively maintains optimal levels. Sublingual or liquid forms may absorb better, particularly in older adults with reduced stomach acid. For those with severe deficiency or absorption issues, B12 injections (1000 mcg weekly or monthly) ensure adequacy. Dietary sources include meat, fish, eggs, and dairy; fortified foods provide B12 for vegetarians, though supplementation is more reliable. For folate, eat leafy green vegetables, legumes, and fortified grains. Supplement with 400-800 mcg daily of methylfolate (L-5-MTHF) or folinic acid, particularly if you have MTHFR genetic variants or elevated homocysteine. Avoid excessive folic acid (synthetic form used in some supplements), which can mask B12 deficiency.
Hormonal Biomarkers and Aging
DHEA-S: Adrenal Reserve and Vitality
Dehydroepiandrosterone sulfate (DHEA-S) is the most abundant steroid hormone, produced primarily by the adrenal glands. DHEA-S serves as a precursor for sex hormone synthesis and has direct effects on immune function, bone density, muscle mass, cognitive function, and mood. DHEA-S levels peak in the mid-20s and decline dramatically with age—by age 70, levels are typically only 10-20% of youthful values.
Optimal DHEA-S levels vary by age and sex. For adults aged 40-60: men should aim for the upper third of the reference range (typically 280-500 μg/dL), women for the middle to upper range (typically 140-270 μg/dL). Maintaining levels in these ranges supports vitality, immune function, and healthy aging. Levels below the 25th percentile for age increase mortality risk.
Research demonstrates that low DHEA-S associates with increased all-cause mortality, cardiovascular disease, frailty, cognitive decline, osteoporosis, reduced immune function, and depression. The Baltimore Longitudinal Study of Aging found that men with DHEA-S in the lowest quartile had significantly higher mortality risk than those in the highest quartile, even after adjusting for other risk factors.
DHEA-S reflects overall adrenal function and stress resilience. Chronic stress, poor sleep, inflammatory diseases, and aging all suppress DHEA-S production. Low DHEA-S may indicate adrenal exhaustion or chronic activation of the stress response (high cortisol suppresses DHEA-S production).
Optimization strategies: Natural strategies to support healthy DHEA-S include: adequate sleep (7-9 hours nightly), regular exercise (but not excessive—overtraining suppresses DHEA-S), stress management practices, maintaining healthy body composition, and possibly adaptogenic herbs like ashwagandha, rhodiola, or ginseng. DHEA supplementation is available and can effectively raise levels: typical doses are 25-50 mg daily for men, 10-25 mg daily for women, taken in the morning. However, DHEA supplementation should be approached cautiously under medical supervision, as DHEA converts to testosterone and estrogen—retest levels after 3 months to ensure appropriate range. Those with hormone-sensitive conditions should avoid DHEA supplementation.
IGF-1: Growth Signaling and Longevity
Insulin-like Growth Factor-1 (IGF-1) is primarily produced by the liver in response to growth hormone. IGF-1 promotes cellular growth, protein synthesis, and tissue maintenance but also stimulates cellular proliferation—potentially accelerating aging and increasing cancer risk when chronically elevated.
The relationship between IGF-1 and longevity is complex and U-shaped: both very high and very low levels increase mortality risk. Animal studies consistently show that reduced IGF-1 signaling extends lifespan, and human studies of centenarians often show lower-than-average IGF-1. However, very low IGF-1 in humans associates with frailty, muscle wasting, osteoporosis, and increased mortality.
Optimal IGF-1 appears to be in the middle to lower-middle range of normal: approximately 120-180 ng/mL for adults, though optimal values vary by age (levels naturally decline with aging). Very high IGF-1 (>250 ng/mL in adults) increases cancer risk, particularly breast, prostate, and colorectal cancer. Very low IGF-1 (<100 ng/mL) impairs tissue maintenance and repair.
The key appears to be maintaining IGF-1 adequate for tissue repair and function but avoiding chronic excessive stimulation of growth pathways. This concept aligns with emerging longevity interventions like protein cycling, time-restricted eating, and periodic fasting—strategies that create periods of low growth signaling while maintaining adequate nutrition.
Management strategies: Modulating IGF-1 involves balancing protein intake, exercise, and possibly periodic fasting. High protein intake (especially animal protein) and chronic overfeeding elevate IGF-1; protein restriction or plant-based diets lower IGF-1. Resistance exercise acutely increases IGF-1 and improves tissue IGF-1 sensitivity. Periodic fasting or fasting-mimicking diets temporarily suppress IGF-1, potentially providing longevity benefits. The optimal approach may be adequate protein and resistance training to maintain muscle mass and function (preventing frailty) combined with periodic fasting or protein cycling to reduce chronic IGF-1 elevation. Individuals with very high IGF-1 should consider reducing animal protein intake; those with very low IGF-1 may benefit from increased protein and resistance training.
Thyroid Hormones: Metabolic Rate and Longevity
Thyroid hormones regulate metabolic rate, energy production, body temperature, heart rate, cognitive function, and virtually every physiological process. Subclinical hypothyroidism (slightly elevated TSH with normal Free T4) affects 5-10% of adults and is more common with aging, particularly in women.
Optimal thyroid function for longevity involves TSH in the range of 1.0-2.0 mIU/L, Free T3 in the middle to upper third of the reference range, and Free T4 in the middle to upper range. While reference ranges for TSH typically extend to 4.0-5.0 mIU/L, research suggests TSH >2.5 mIU/L may indicate subclinical hypothyroidism with symptoms including fatigue, weight gain, cold intolerance, cognitive slowing, and mood disturbances.
Interestingly, the relationship between thyroid hormones and longevity shows some complexity. Very high thyroid function (hyperthyroidism) clearly increases mortality risk through cardiovascular effects. However, some centenarian studies show slightly lower-than-average thyroid hormone levels, possibly reflecting reduced metabolic rate consistent with longevity. The key appears to be avoiding overt hypothyroidism while not pushing function to excessive levels—maintaining thyroid hormones in the middle-to-upper normal range.
Optimization strategies: If thyroid function is suboptimal, address nutritional factors: adequate iodine (from iodized salt, seafood, or kelp—but avoid excessive iodine which can suppress thyroid function), selenium (Brazil nuts are an excellent source—2-3 daily provide adequate selenium), iron (iron deficiency impairs thyroid hormone production), and zinc. Avoid goitrogenic compounds in excess (found in raw cruciferous vegetables—cooking inactivates them). If TSH >2.5 with symptoms, discuss thyroid hormone replacement with your doctor. Levothyroxine (synthetic T4) is standard treatment; some people benefit from combination T4/T3 therapy. Regular monitoring ensures appropriate dosing.
Organ Function and Longevity
Kidney Function: eGFR and Creatinine
Kidney function is a powerful longevity biomarker, yet gradual decline is often dismissed as "normal aging." The estimated Glomerular Filtration Rate (eGFR) measures kidney filtering capacity: optimal eGFR is >90 mL/min/1.73m², levels 60-89 indicate mild decline, 30-59 moderate decline (stage 3 chronic kidney disease), and <30 severe decline requiring specialist care.
Even mild kidney function decline significantly increases cardiovascular mortality risk, progression to kidney failure, anemia, bone disease, and complications from medications cleared by the kidneys. The Chronic Kidney Disease Prognosis Consortium meta-analysis of over 2 million individuals demonstrated that eGFR <60 mL/min/1.73m² increases mortality risk approximately 50% compared to eGFR >90, with risk increasing progressively as eGFR declines.
Serum creatinine (used to calculate eGFR) should be as low as reasonably achievable: optimal is <1.0 mg/dL for men, <0.9 mg/dL for women. Very low creatinine may indicate muscle wasting, while rising creatinine over time indicates declining kidney function. Annual monitoring of creatinine and eGFR enables early detection of kidney disease.
Kidney function decline accelerates aging through multiple mechanisms: accumulation of uremic toxins, activation of inflammatory pathways, hormonal imbalances (erythropoietin deficiency causing anemia, vitamin D deficiency, parathyroid hormone elevation), and cardiovascular disease progression. Protecting kidney function is essential for longevity.
Protection strategies: Maintain excellent blood pressure control (target <120/80 mmHg), optimal glycemic control (high glucose damages kidneys), adequate hydration, healthy body weight, avoid nephrotoxic medications (NSAIDs like ibuprofen with long-term use, some antibiotics), limit excessive protein intake (very high protein stresses kidneys), and manage cardiovascular risk factors. ACE inhibitors or ARBs (blood pressure medications) provide kidney protection in those with hypertension or diabetes. Regular monitoring enables early intervention before significant damage occurs.
Liver Function: GGT and Transaminases
Gamma-glutamyl transferase (GGT) is a liver enzyme that, even within normal ranges, independently predicts cardiovascular disease, diabetes, cancer, and all-cause mortality. Optimal GGT for longevity is <20 U/L despite reference ranges extending to 50-70 U/L. Studies show that GGT in the upper-normal range (30-50 U/L) carries significantly higher mortality risk than levels <20 U/L.
Elevated GGT indicates oxidative stress, inflammation, and often fatty liver disease—even before other liver enzymes (ALT, AST) rise. GGT elevation commonly occurs with insulin resistance, obesity, alcohol consumption, and metabolic syndrome. GGT appears to be both a marker and mediator of oxidative stress and inflammation.
Other liver markers for longevity include ALT (alanine aminotransferase) and AST (aspartate aminotransferase). Optimal ALT is <25 U/L for men, <19 U/L for women; optimal AST is <30 U/L. The AST/ALT ratio provides additional information: ratio <1 suggests fatty liver disease, ratio >2 may indicate alcoholic liver disease or advanced fibrosis.
Optimization strategies: Lowering GGT and improving liver health requires: weight loss if overweight (reducing visceral fat), limiting or eliminating alcohol, reducing sugar and refined carbohydrate intake (which drive fatty liver), regular exercise, coffee consumption (coffee is strongly protective against liver disease), and addressing insulin resistance. Supplements with evidence for liver health include milk thistle (silymarin), N-acetylcysteine (NAC), and omega-3 fatty acids. Many people see dramatic GGT reductions (30-50%) with weight loss and dietary improvements within 3-6 months.
Comprehensive Longevity Biomarker Panel
An optimal longevity-focused blood panel should comprehensively assess metabolic health, cardiovascular risk, inflammation, hormones, nutrients, and organ function. The following represents a thorough baseline assessment:
Metabolic Health: HbA1c, Fasting Glucose, Fasting Insulin, Lipid Panel (Total Cholesterol, LDL, HDL, Triglycerides, ApoB, Lipoprotein(a)), Uric Acid
Inflammation & Immunity: hs-CRP, Homocysteine, Complete Blood Count (including WBC differential), Erythrocyte Sedimentation Rate (ESR), Ferritin
Kidney & Liver Function: Comprehensive Metabolic Panel (glucose, creatinine, eGFR, BUN, electrolytes, calcium, ALT, AST, ALP, GGT, total protein, albumin)
Hormones: Thyroid Panel (TSH, Free T3, Free T4, thyroid antibodies if indicated), DHEA-S, Cortisol (AM), Sex Hormones appropriate to age and sex (Total and Free Testosterone, Estradiol, Progesterone, SHBG), IGF-1
Vitamins & Minerals: Vitamin D 25(OH)D, Vitamin B12, Folate (serum and RBC), Iron Panel (ferritin, serum iron, TIBC, transferrin saturation), Magnesium (RBC magnesium preferred), Omega-3 Index
Advanced Optional Markers: Advanced Lipid Panel (LDL particle number, particle size, Apolipoprotein A1), Insulin-like Growth Factor Binding Protein 3 (IGFBP-3), Hemoglobin A1c 5-year trajectory, Biological Age testing (epigenetic clocks like GlycanAge or TruAge), Micronutrient testing for comprehensive assessment
This comprehensive panel, tested annually with more frequent monitoring of specific markers during intervention periods, provides the data foundation for personalized longevity optimization. Trends over multiple years become even more valuable than single time points, revealing trajectories toward health optimization or decline.
Interpreting Results for Optimization
Interpreting longevity biomarkers requires understanding that "normal" laboratory ranges differ fundamentally from "optimal" ranges for health and longevity. Reference ranges are statistical constructs based on population data—including unhealthy individuals—and indicate values unlikely to cause immediate disease, not values that support maximal healthspan.
When reviewing your results, compare values to optimal ranges discussed throughout this guide rather than simply seeking "within normal range" on laboratory reports. Many people have multiple biomarkers in the normal range but far from optimal—these suboptimal values predict future disease risk and accelerated aging decades in advance.
Focus on patterns and clusters: insulin resistance typically presents as elevated fasting insulin, rising HbA1c (even if still <5.7%), high triglycerides, low HDL, elevated ApoB, and increased hs-CRP. This metabolic syndrome pattern demands intervention regardless of whether individual markers have crossed "abnormal" thresholds.
Track trends over time: a slowly rising HbA1c (from 5.0% to 5.3% to 5.5% over several years) warns of progression toward diabetes despite remaining "normal." Rising homocysteine, declining eGFR, or increasing hs-CRP should prompt investigation and intervention rather than waiting for abnormal values.
Prioritize interventions based on your specific pattern: if metabolic markers dominate (high insulin, HbA1c, triglycerides), focus intensely on diet modification, weight loss if needed, and exercise. If inflammation is elevated (high hs-CRP, upper-normal WBC), investigate sources (obesity, poor diet, poor sleep, chronic stress, infections) and implement anti-inflammatory strategies. If nutrient deficiencies appear, implement targeted supplementation and retest to verify correction.
Work with qualified practitioners—functional medicine doctors, longevity physicians, or informed GPs—to interpret results comprehensively and develop personalized optimization strategies. While biomarker testing is increasingly accessible, interpreting results and developing effective interventions benefits from medical expertise.
Implementing Biomarker-Guided Longevity
Blood biomarker tracking transforms longevity from abstract goal to measurable, optimizable process. Regular comprehensive testing provides objective feedback on interventions, early detection of dysfunction before disease develops, and personalized data to guide nutrition, lifestyle, supplementation, and medical decisions.
Begin with comprehensive baseline testing as outlined in this guide, then retest annually or more frequently during active optimization. Focus on achieving and maintaining optimal ranges rather than settling for "normal" values. Track trends meticulously—longitudinal data over years becomes invaluable for personalized health optimization.
Remember that biomarkers represent intermediate endpoints: the ultimate goals are extended healthspan, maintained function, vitality, and prevention of age-related disease. Use biomarker data as a tool for achieving these goals, not as ends in themselves. Combine quantitative biomarker optimization with qualitative measures of health: energy, sleep quality, cognitive function, physical performance, and subjective wellbeing.
The science of longevity biomarkers continues advancing rapidly, with emerging markers including epigenetic aging clocks, inflammatory cytokine panels, advanced metabolomics, and proteomics offering increasingly precise assessment of biological age and health status. Stay informed about advances while focusing on well-established markers with clear evidence for longevity associations.
Ultimately, biomarker-guided health optimization represents proactive, preventive medicine—identifying and addressing dysfunction years or decades before clinical disease emerges. This approach, increasingly accessible through private testing services and emerging as the standard in longevity medicine, empowers individuals to take control of their healthspan and potentially extend not just years of life, but years of vigorous, healthy life.