Biomarkers - General Function / Cardiovascular
General Function / Cardiovascular
This section documents TILDA biomarkers currently grouped under general function and cardiovascular health, including lipid measures, nutritional markers, metabolic and growth-related proteins, neurotrophic and cardiac markers, and metabolomic profiling.
General Function / Cardiovascular Biomarkers
Click each heading to expand details of this biomarker.
Overview
What is it? Total cholesterol measures the total amount of cholesterol circulating in the blood. Cholesterol is a lipid that is synthesised in several tissues, particularly the liver and intestinal wall, and is also obtained through dietary intake.
Research relevance: Can be used to investigate lipid metabolism and cardiovascular health, including associations between cholesterol levels and atherosclerotic and cardiovascular disease risk.
Sample type: Fresh lithium-heparin plasma
Sample Collection / Handling
Plasma isolated from 5 mL of fresh whole blood and refrigerated at 2–4°C for 48 hours.
Assay / Measurement
Method: Enzymatic colorimetric assay for the direct quantitative determination of total cholesterol in plasma.
Equipment / analyser: Wave 1: Siemens Dimension Xpand chemistry kits and analyser. Waves 3 and 6: Roche Hitachi Cobas c 701 analyser with Roche Cobas Cholesterol Gen2 kits.
Laboratory: Wave 1: Prospec Laboratories, Clane Hospital, Co. Kildare. Waves 3 and 6: Biochemistry Department, Laboratory Medicine (LabMed), St James’s Hospital, Dublin.
Measurement Characteristics
| Characteristic | Value |
|---|---|
| Units | mmol/L |
| Measurement range | 0.1-20.7 mmol/L |
| Lower detection limit | 0.1 mmol/L |
| Assay CoV | 0.016 |
Collection Waves
| Biomarker | Wave 1 | Wave 2 | Wave 3 | Wave 4 | Wave 5 | Wave 6 |
|---|---|---|---|---|---|---|
| Total Cholesterol | X | X | X |
Reference
- National Library of Medicine (2024) Cholesterol levels. MedlinePlus. Available at: https://medlineplus.gov/lab-tests/cholesterol-levels/ 26 August 2026).
Example TILDA Papers
- Murphy C, Shelley E, O Halloran AM, Fahey T, Kenny RA. Failure to control hypercholesterolaemia in the Irish adult population: Cross-sectional analysis of the baseline wave of The Irish Longitudinal Study on Ageing (TILDA). Ir J Med Sci. 2017. 186: 1009–1017. https://doi.org/10.1007/s11 845-017-1590-3.
Overview
What is it? High-density lipoprotein cholesterol (HDL-C) measures the cholesterol carried by high-density lipoproteins. HDL transports cholesterol from peripheral tissues back to the liver, where it can be removed from the body.
Research relevance: Can be used to investigate lipid metabolism and cardiovascular health, including associations between HDL-C levels and risk of atherosclerotic and cardiovascular disease.
Sample type: Fresh lithium-heparin plasma
Sample Collection / Handling
Plasma isolated from 5 mL of fresh whole blood and refrigerated at 2–4°C for 48 hours.
Assay / Measurement
Method: Homogeneous enzymatic colorimetric assay for the direct quantitative determination of HDL-C in plasma.
Equipment / analyser: Wave 1: Siemens Dimension Xpand chemistry kits and analyser. Waves 3 and 6: Roche Hitachi Cobas c 701 analyser with Roche Cobas HDL Cholesterol Plus Gen3 kits.
Laboratory: Wave 1: Prospec Laboratories, Clane Hospital, Co. Kildare. Waves 3 and 6: Biochemistry Department, Laboratory Medicine (LabMed), St James’s Hospital, Dublin.
Measurement Characteristics
| Characteristic | Value |
|---|---|
| Units | mmol/L |
| Measurement range | 0.08-3.12 mmol/L |
| Lower detection limit | 0.08 mmol/L |
| Assay CoV | 0.015 |
Collection Waves
| Biomarker | Wave 1 | Wave 2 | Wave 3 | Wave 4 | Wave 5 | Wave 6 |
|---|---|---|---|---|---|---|
| High Density Lipoprotein Cholesterol (HDL-C) | X | X | X |
Reference
- National Library of Medicine (2026) HDL: The “Good” Cholesterol. MedlinePlus. Available at: MedlinePlus — HDL: The “Good” Cholesterol
Example TILDA Papers
- Murphy C, Shelley E, O Halloran AM, Fahey T, Kenny RA. Failure to control hypercholesterolaemia in the Irish adult population: Cross-sectional analysis of the baseline wave of The Irish Longitudinal Study on Ageing (TILDA). Ir J Med Sci. 2017. 186: 1009–1017. https://doi.org/10.1007/s11 845-017-1590-3.
Overview
What is it? Triglycerides are a type of fat found in the blood. They are derived from dietary fats and are also produced by the body from excess energy, with circulating triglycerides transported primarily in lipoproteins such as VLDL and chylomicrons.
Research relevance: Can be used to investigate lipid metabolism and cardiometabolic health, including associations between triglyceride levels and dyslipidaemia, metabolic syndrome and cardiovascular disease risk.
Sample type: Fresh lithium-heparin plasma
Sample Collection / Handling
Plasma isolated from 5 mL of fresh whole blood and refrigerated at 2–4°C for 48 hours.
Assay / Measurement
Method: GPO-PAP enzymatic colorimetric assay for the direct quantitative determination of triglycerides in plasma.
Equipment / analyser: Wave 1: Siemens Dimension Xpand chemistry kits and analyser. Waves 3 and 6: Roche Hitachi Cobas c 701 analyser with Roche Cobas HDL Cholesterol Plus Gen3 kits.
Laboratory: Wave 1: Prospec Laboratories, Clane Hospital, Co. Kildare. Waves 3 and 6: Biochemistry Department, Laboratory Medicine (LabMed), St James’s Hospital, Dublin.
Measurement Characteristics
| Characteristic | Value |
|---|---|
| Units | mmol/L |
| Measurement range | 0.1‑10.0 mmol/L |
| Lower detection limit | 0.1 mmol/L |
| Assay CoV | 0.023 |
Collection Waves
| Biomarker | Wave 1 | Wave 2 | Wave 3 | Wave 4 | Wave 5 | Wave 6 |
|---|---|---|---|---|---|---|
| Triglycerides | X | X | X |
Reference
- National Library of Medicine (2024) Triglycerides Test. MedlinePlus. Available at: https://medlineplus.gov/lab-tests/triglycerides-test/
Example TILDA Papers
- Murphy C, Shelley E, O Halloran AM, Fahey T, Kenny RA. Failure to control hypercholesterolaemia in the Irish adult population: Cross-sectional analysis of the baseline wave of The Irish Longitudinal Study on Ageing (TILDA). Ir J Med Sci. 2017. 186: 1009–1017. https://doi.org/10.1007/s11 845-017-1590-3.
Overview
What is it? Low-density lipoprotein cholesterol (LDL-C) represents cholesterol carried by low-density lipoproteins, which transport cholesterol through the circulation to peripheral tissues and the liver.
Research relevance: Can be used to investigate lipid metabolism and cardiovascular health, including associations between LDL-C levels, atherosclerosis and risk of cardiovascular disease.
Sample type: Fresh lithium-heparin plasma
Sample Collection / Handling
Plasma isolated from 5 mL of fresh whole blood and refrigerated at 2–4°C for 48 hours.
Assay / Measurement
Method: LDL-C was indirectly determined using an automated calculation based on the Friedewald equation: LDL-C (mmol/L) = TC − HDL − (TG × 0.46). LDL-C was calculated only for participants with triglyceride concentrations <4.0 mmol/L.
Laboratory: Calculation automated at the Biochemistry Department, Laboratory Medicine (LabMed), St James’s Hospital, Dublin.
Measurement Characteristics
| Characteristic | Value |
|---|---|
| Units | mmol/L |
Collection Waves
| Biomarker | Wave 1 | Wave 2 | Wave 3 | Wave 4 | Wave 5 | Wave 6 |
|---|---|---|---|---|---|---|
| Low-Density Lipoprotein Cholesterol | X | X | X |
Reference
- National Library of Medicine (2024) LDL: The “Bad” Cholesterol. MedlinePlus. Available at: https://medlineplus.gov/ldlthebadcholesterol.html
Example TILDA Papers
- Murphy C, Shelley E, O Halloran AM, Fahey T, Kenny RA. Failure to control hypercholesterolaemia in the Irish adult population: Cross-sectional analysis of the baseline wave of The Irish Longitudinal Study on Ageing (TILDA). Ir J Med Sci. 2017. 186: 1009–1017. https://doi.org/10.1007/s11 845-017-1590-3.
Other References
- Wang TY, Haddad M, Wang TS. Low triglyceride levels affect calculation of low-density lipoprotein cholesterol values. Arch Pathol Lab Med. 2001;125(3):404–405
Overview
What is it? Lipoprotein(a) [Lp(a)] is a cholesterol-rich lipoprotein consisting of an LDL-like particle bound to apolipoprotein(a). Circulating Lp(a) concentrations are largely genetically determined and vary considerably between individuals.
Research relevance: Can be used to investigate genetically influenced cardiovascular risk, including associations between Lp(a) concentrations, atherosclerotic cardiovascular disease and aortic valve stenosis.
Sample type: Fresh lithium-heparin plasma
Sample Collection / Handling
Plasma isolated from 5 mL of fresh whole blood and refrigerated at 2–4°C for 48 hours.
Assay / Measurement
Method: Particle-enhanced immunoturbidimetric assay. Lp(a) in the sample agglutinates with latex particles coated with anti-Lp(a) antibodies, with the resulting precipitate measured turbidimetrically at 659 nm.
Equipment / analyser: Wave 6: Roche Hitachi Cobas c 701 analyser with Roche Cobas Tina-quant Lipoprotein(a) Gen.2 kits.
Laboratory: Wave 6: Biochemistry Department, Laboratory Medicine (LabMed), St James’s Hospital, Dublin.
Measurement Characteristics
| Characteristic | Value |
|---|---|
| Units | nmol/L |
| Measurement range | 7.0-240.0 nmol/L |
| Lower detection limit | 7.0 mmol/L |
| Assay CoV | 0.042 |
Collection Waves
| Biomarker | Wave 1 | Wave 2 | Wave 3 | Wave 4 | Wave 5 | Wave 6 |
|---|---|---|---|---|---|---|
| Lipoprotein(a) | X |
Reference
- Kronenberg, F., Mora, S., Stroes, E.S.G., Ference, B.A., Arsenault, B.J., Berglund, L., Dweck, M.R., Koschinsky, M., Lambert, G., Mach, F., McNeal, C.J., Moriarty, P.M., Natarajan, P., Nordestgaard, B.G., Parhofer, K.G., Virani, S.S., von Eckardstein, A., Watts, G.F., Stock, J.K., Ray, K.K. and Tsimikas, S. (2022) ‘Lipoprotein(a) in atherosclerotic cardiovascular disease and aortic stenosis: a European Atherosclerosis Society consensus statement’, European Heart Journal, 43(39), pp. 3925–3946. doi:10.1093/eurheartj/ehac361.
Example TILDA Papers
- In press TILDA report is forthcoming and will be published in HRB Open Research in Q4 2024.
Overview
What is it? Vitamin D is obtained through skin synthesis following sunlight exposure, dietary sources and supplements. Circulating 25-hydroxyvitamin D [25(OH)D] is the principal indicator of vitamin D status and includes contributions from vitamin D2 and vitamin D3. Vitamin D plays an important role in calcium and phosphate regulation and bone health.
Research relevance: Can be used to investigate vitamin D status and its associations with bone and musculoskeletal health, nutritional status and other health outcomes in ageing populations.
Sample type: Frozen K2EDTA blood plasma
Sample Collection / Handling
Plasma isolated from 10 mL of fresh whole blood, maintained at 2–4°C for 24–48 hours after blood collection and subsequently frozen at −80°C.
Assay / Measurement
Method: Total plasma 25-hydroxyvitamin D [25(OH)D2 and 25(OH)D3] was quantified using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method (MassChrom 25-OH-Vitamin D3/D2, Chromsystems). Method quality was monitored using internal quality controls, NIST 972 vitamin D standard reference material and participation in DEQAS.
Equipment / analyser: API 4000 LC-MS/MS system (AB SCIEX) with MassChrom 25-OH-Vitamin D3/D2 (Chromsystems Instruments and Chemicals GmbH).
Laboratory: Biochemistry Department, Laboratory Medicine (LabMed), St James’s Hospital, Dublin.
Measurement Characteristics
| Characteristic | Value |
|---|---|
| Units | nmol/L |
| Measurement range | 1.0-650 (nmol/L) |
| Lower detection limit | 1.0 (nmol/L) |
| Assay CoV | 0.045 |
Collection Waves
| Biomarker | Wave 1 | Wave 2 | Wave 3 | Wave 4 | Wave 5 | Wave 6 |
|---|---|---|---|---|---|---|
| Vitamin D3 | X | X |
Reference
- National Institutes of Health, Office of Dietary Supplements (2025) Vitamin D: Fact Sheet for Health Professionals. Available at: https://ods.od.nih.gov/factsheets/VitaminD-HealthProfessional/
Example TILDA Papers
- Laird E, O’Halloran AM, Carey D, Healy M, O’Connor D, Moore P, Shannon T, Molloy AM, Kenny RA. The prevalence of vitamin D deficiency and the determinants of 25(OH)D concentration in older Irish adults: Data from The Irish Longitudinal Study on Ageing (TILDA). J Gerontol A Biol Sci Med Sci [01 Mar 2018, 73(4):519-525] https://doi.org/10.1093/gerona/glx168
- O’Halloran AM, Laird EJ, Feeney J, Healy M, Moran R, Beatty S, Nolan JM, Molloy AM, Kenny RA. Circulating Micronutrient Biomarkers Are Associated With 3 Measures of Frailty: Evidence From the Irish Longitudinal Study on Ageing. J Am Med Dir Assoc. 2020 Feb;21(2):240-247.e5. https://doi.org/10.1016/j.jamda.2019.06.011
Overview
What is it? Folate (vitamin B9) is a water-soluble B vitamin involved in one-carbon metabolism. It is required for DNA and RNA synthesis, normal cell division and amino acid metabolism, including the conversion of homocysteine to methionine.
Research relevance: Can be used to investigate folate and nutritional status and their associations with one-carbon metabolism and circulating homocysteine. In ageing research, folate status can also be examined in relation to cognitive and cardiovascular health.
Sample type: Frozen K2EDTA blood plasma
Sample Collection / Handling
Plasma isolated from 10 mL of fresh whole blood, maintained at 2–4°C for 24–48 hours after blood collection and subsequently frozen at −80°C.
Assay / Measurement
Method: Microbiological assay using Lactobacillus casei as the test organism. Ascorbic acid was used to protect folate activity during measurement.
Laboratory: Molloy Nutrition Research Laboratory, Trinity Translational Medicine Institute (TTMI), St James’s Hospital, Dublin.
Measurement Characteristics
| Characteristic | Value |
|---|---|
| Units | nmol/L |
| Measurement range | 1.0-650 (nmol/L) |
| Lower detection limit | 1.0 (nmol/L) |
| Assay CoV | 0.109 |
Collection Waves
| Biomarker | Wave 1 | Wave 2 | Wave 3 | Wave 4 | Wave 5 | Wave 6 |
|---|---|---|---|---|---|---|
| Folate (Vitamin B9) | X |
Reference
- National Institutes of Health, Office of Dietary Supplements (2022) Folate: Fact Sheet for Consumers. Available at: https://ods.od.nih.gov/factsheets/Folate-Consumer/
Example TILDA Papers
- Molloy AM, Scott JM (1997). Microbiological assay for serum, plasma, and red cell folate using cryopreserved, microtiter plate method. Methods Enzymol 281, 43-53.
- Laird EJ, O’Halloran AM, Carey D, O’Connor D, Kenny RA, Molloy AM. Voluntary fortification is ineffective to maintain the vitamin B12 and folate status of older Irish adults: evidence from the Irish Longitudinal Study on Ageing (TILDA). Br J Nutr 01 Jul 2018, 120(1):111-120 https://doi.org/10.1017/S0007114518001356
- O’Halloran AM, Laird EJ, Feeney J, Healy M, Moran R, Beatty S, Nolan JM, Molloy AM, Kenny RA. Circulating Micronutrient Biomarkers Are Associated With 3 Measures of Frailty: Evidence From the Irish Longitudinal Study on Ageing. J Am Med Dir Assoc. 2020 Feb;21(2):240-247.e5. https://doi.org/10.1016/j.jamda.2019.06.011
Overview
What is it? Vitamin B12 (cobalamin) is a water-soluble vitamin required for normal red blood cell formation, DNA synthesis and neurological function. Its metabolically active forms act as cofactors in reactions involved in one-carbon and amino acid metabolism.
Research relevance: Can be used to investigate vitamin B12 and nutritional status, particularly in older adults who are at increased risk of deficiency. Vitamin B12 status can also be examined in relation to haematological and neurological health, cognitive function and homocysteine metabolism.
Sample type: Frozen K2EDTA blood plasma
Sample Collection / Handling
Plasma isolated from 10 mL of fresh whole blood, maintained at 2–4°C for 24–48 hours after blood collection and subsequently frozen at −80°C.
Assay / Measurement
Method: Microbiological assay performed on microtitre plates using a colistin sulphate-resistant strain of Lactobacillus leichmannii (NCIB 12519) and cryopreserved cultures.
Laboratory: Molloy Nutrition Research Laboratory, Trinity Translational Medicine Institute (TTMI), St James’s Hospital, Dublin.
Measurement Characteristics
| Characteristic | Value |
|---|---|
| Units | pmol/L |
| Measurement range | 28-2000 (pmol/L) |
| Lower detection limit | 28.0 (pmol/L) |
| Assay CoV | 0.109 |
Collection Waves
| Biomarker | Wave 1 | Wave 2 | Wave 3 | Wave 4 | Wave 5 | Wave 6 |
|---|---|---|---|---|---|---|
| Vitamin B12 (Cobalamin) | X |
Reference
- National Institutes of Health, Office of Dietary Supplements (2025) Vitamin B12: Fact Sheet for Health Professionals. Available at: https://ods.od.nih.gov/factsheets/VitaminB12-HealthProfessional/
Example TILDA Papers
- Laird EJ, O’Halloran AM, Carey D, O’Connor D, Kenny RA, Molloy AM. Voluntary fortification is ineffective to maintain the vitamin B12 and folate status of older Irish adults: evidence from the Irish Longitudinal Study on Ageing (TILDA). Br J Nutr 01 Jul 2018, 120(1):111-120 https://doi.org/10.1017/S0007114518001356
- O’Halloran AM, Laird EJ, Feeney J, Healy M, Moran R, Beatty S, Nolan JM, Molloy AM, Kenny RA. Circulating Micronutrient Biomarkers Are Associated With 3 Measures of Frailty: Evidence From the Irish Longitudinal Study on Ageing. J Am Med Dir Assoc. 2020 Feb;21(2):240-247.e5. https://doi.org/10.1016/j.jamda.2019.06.011
Other References
- Kelleher BP, Broin SD (1991) Microbiological assay for vitamin B12 performed in 96-well microtitre plates. J Clin Pathol 44, 592-595.
Overview
What is it? Adiponectin is an adipokine, a signalling protein secreted predominantly by adipose tissue. It is involved in the regulation of glucose and lipid metabolism, insulin sensitivity and inflammatory processes. Circulating adiponectin concentrations are generally lower in individuals with obesity and insulin resistance.
Research relevance: Can be used to investigate adipose tissue function and metabolic health, including associations between adiponectin concentrations, obesity, insulin resistance, metabolic syndrome and cardiovascular health. In ageing research, it can also be examined in relation to changes in body composition and cardiometabolic health outcomes.
Sample type: Frozen K2EDTA blood plasma
Sample Collection / Handling
Plasma isolated from 10 mL of fresh whole blood, maintained at 2–4°C for 24–48 hours after blood collection and subsequently frozen at −80°C.
Assay / Measurement
Method: Single-plex immunoassay using the Meso Scale Diagnostics (MSD) R-PLEX platform. Assays were conducted according to the manufacturer’s instructions, and adiponectin concentrations were calculated using MSD Discovery Workbench Software (v4.0).
Equipment / analyser: SECTOR Imager 6000 (Meso Scale Discovery)
Laboratory: Central Biotechnology Services, Cardiff University, Cardiff, UK
Measurement Characteristics
| Characteristic | Value |
|---|---|
| Units | pg/mL |
| Measurement range | 10.3e+03- 2.00e+08 pg/ml |
| Lower detection limit | 10.3e+03pg/ml |
| Assay CoV | 0.188 |
Collection Waves
| Biomarker | Wave 1 | Wave 2 | Wave 3 | Wave 4 | Wave 5 | Wave 6 |
|---|---|---|---|---|---|---|
| Adiponectin | X | X |
Reference
- Achari, A.E. and Jain, S.K. (2017) ‘Adiponectin, a therapeutic target for obesity, diabetes, and endothelial dysfunction’, International Journal of Molecular Sciences, 18(6), p. 1321. doi:10.3390/ijms18061321.
Other References
- Li N, Zhao S, Zhang Z, Zhu Y, Gliniak CM, Vishvanath L, An YA, Wang MY, Deng Y, Zhu Q, Shan B, Sherwood A, Onodera T, Oz OK, Gordillo R, Gupta RK, Liu M, Horvath TL, Dixit VD, Scherer PE. Adiponectin preserves metabolic fitness during aging. Elife. 2021 Apr 27;10:e65108. https://doi.org/10.7554%2FeLife.65108
- Mancuso P, Bouchard B. The Impact of Aging on Adipose Function and Adipokine Synthesis. Front Endocrinol (Lausanne). 2019 Mar 11;10:137. https://doi.org/10.3389/fendo.2019.00137
- Günther A, Becker M, Göpfert J, Joos T, Schneiderhan-Marra N. Comparison of Bead-Based Fluorescence Versus Planar Electrochemiluminescence Multiplex Immunoassays for Measuring Cytokines in Human Plasma. Front Immunol. 2020 Sep 24;11:572634. https://doi.org/10.3389/fimmu.2020.572634
Overview
What is it? Brain-derived neurotrophic factor (BDNF) is a neurotrophin that supports the survival, growth and function of neurons. It plays an important role in synaptic plasticity and processes involved in learning and memory and is widely expressed in the central nervous system and peripheral tissues.
Research relevance: Can be used to investigate neurobiological processes related to neuronal health and plasticity. In ageing research, circulating BDNF can be examined in relation to cognitive function, cognitive decline, neurodegenerative disease and mental health outcomes.
Sample type: Frozen K2EDTA blood plasma
Sample Collection / Handling
Plasma isolated from 10 mL of fresh whole blood, maintained at 2–4°C for 24–48 hours after blood collection and subsequently frozen at −80°C.
Assay / Measurement
Method: Single-plex immunoassay using the Meso Scale Diagnostics (MSD) U-PLEX platform. Assays were conducted according to the manufacturer’s instructions, and BDNF concentrations were calculated using MSD Discovery Workbench Software (v4.0).
Equipment / analyser: SECTOR Imager 6000 (Meso Scale Discovery)
Laboratory: Central Biotechnology Services, Cardiff University, Cardiff, UK
Measurement Characteristics
| Characteristic | Value |
|---|---|
| Units | pg/mL |
| Measurement range | 0.72 - 16400 pg/ml |
| Lower detection limit | 0.72 pg/ml |
| Assay CoV | 0.121 |
Collection Waves
| Biomarker | Wave 1 | Wave 2 | Wave 3 | Wave 4 | Wave 5 | Wave 6 |
|---|---|---|---|---|---|---|
| Brain-Derived Neurotrophic Factor | X | X |
Reference
- Miranda, M., Morici, J.F., Zanoni, M.B. and Bekinschtein, P. (2019) ‘Brain-derived neurotrophic factor: a key molecule for memory in the healthy and the pathological brain’, Frontiers in Cellular Neuroscience, 13, p. 363. doi:10.3389/fncel.2019.00363.
Other References
- Molinari C, Morsanuto V, Ruga S, Notte F, Farghali M, Galla R, Uberti F. The Role of BDNF on Aging-Modulation Markers. Brain Sci. 2020 May 9;10(5):285. https://doi.org/10.3390%2Fbrainsci10050285
- Oh H, Lewis DA, Sibille E. The Role of BDNF in Age-Dependent Changes of Excitatory and Inhibitory Synaptic Markers in the Human Prefrontal Cortex. Neuropsychopharmacology. 2016 Dec;41(13):3080-3091. https://doi.org/10.1038/npp.2016.126
- Miranda M, Morici JF, Zanoni MB, Bekinschtein P. Brain-Derived Neurotrophic Factor: A Key Molecule for Memory in the Healthy and the Pathological Brain. Front Cell Neurosci. 2019 Aug 7;13:363. https://doi.org/10.3389/fncel.2019.00363
Overview
What is it? Growth differentiation factor-15 (GDF-15) is a stress-responsive signalling protein and member of the transforming growth factor-beta superfamily. Circulating levels are generally low under normal physiological conditions but can increase in response to cellular stress, inflammation and tissue injury, and tend to increase with age.
Research relevance: Can be used to investigate biological stress and age-related changes in health. In ageing research, circulating GDF-15 can be examined in relation to frailty, functional decline, cardiovascular and kidney health, multimorbidity and mortality.
Sample type: Frozen K2EDTA blood plasma
Sample Collection / Handling
Plasma isolated from 10 mL of fresh whole blood, maintained at 2–4°C for 24–48 hours after blood collection and subsequently frozen at −80°C.
Assay / Measurement
Method: Single-plex immunoassay using the Meso Scale Diagnostics (MSD) R-PLEX platform. Assays were conducted according to the manufacturer’s instructions, and GDF-15 concentrations were calculated using MSD Discovery Workbench Software (v4.0).
Equipment / analyser: SECTOR Imager 6000 (Meso Scale Discovery)
Laboratory: Central Biotechnology Services, Cardiff University, Cardiff, UK
Measurement Characteristics
| Characteristic | Value |
|---|---|
| Units | pg/mL |
| Measurement range | 1.00 – 50,000 pg/ml |
| Lower detection limit | 1.00 pg/ml |
| Assay CoV | 0.096 |
Collection Waves
| Biomarker | Wave 1 | Wave 2 | Wave 3 | Wave 4 | Wave 5 | Wave 6 |
|---|---|---|---|---|---|---|
| Growth Differentiation Factor-15 | X | X |
Reference
- Conte, M., Martucci, M., Mosconi, G., Chiariello, A., Cappuccilli, M., Totti, V., Santoro, A., Franceschi, C. and Salvioli, S. (2020) ‘GDF15 plasma level is inversely associated with level of physical activity and correlates with markers of inflammation and muscle weakness’, Frontiers in Immunology, 11, 915. doi:10.3389/fimmu.2020.00915.
Other References
- Nowak N, De Looze C, O’Halloran A, Kenny RA, Sexton DJ. The association between kidney function, cognitive function, and structural brain abnormalities in community-dwelling individuals aged 50+ is mediated by age and biomarkers of cardiovascular disease. Cardiovasc Res. 2023 Sep 5;119(11):2106-2116. https://doi.org/10.1093/cvr/cvad060
- Conte M, Giuliani C, Chiariello A, Iannuzzi V, Franceschi C, Salvioli S. GDF15, an emerging key player in human aging. Ageing Res Rev. 2022 Mar;75:101569. https://doi.org/10.1016/j.arr.2022.101569
- Pence BD. Growth Differentiation Factor-15 in Immunity and Aging. Front Aging. 2022 Feb 9;3:837575. https://doi.org/10.3389%2Ffragi.2022.837575
- Moon JS, Goeminne LJE, Kim JT, Tian JW, Kim SH, Nga HT, Kang SG, Kang BE, Byun JS, Lee YS, Jeon JH, Shong M, Auwerx J, Ryu D, Yi HS. Growth differentiation factor 15 protects against the aging-mediated systemic inflammatory response in humans and mice. Aging Cell. 2020 Aug;19(8):e13195. https://doi.org/10.1111/acel.13195
Overview
What is it? Insulin-like growth factor-1 (IGF-1) is a hormone that mediates many of the effects of growth hormone and plays an important role in growth, metabolism and the maintenance of multiple tissues. Circulating IGF-1 concentrations generally decline with advancing age.
Research relevance: Can be used to investigate growth hormone/IGF-1 signalling, metabolic regulation and age-related changes in anabolic function. In ageing research, IGF-1 can also be examined in relation to physical function, frailty, cardiovascular health and mortality.
Sample type: Frozen K2EDTA blood plasma
Sample Collection / Handling
Plasma isolated from 10 mL of fresh whole blood, maintained at 2–4°C for 24–48 hours after blood collection and subsequently frozen at −80°C.
Assay / Measurement
Method: Single-plex immunoassay using the Meso Scale Diagnostics (MSD) R-PLEX platform. Assays were conducted according to the manufacturer’s instructions, and IGF-1 concentrations were calculated using MSD Discovery Workbench Software (v4.0).
Equipment / analyser: SECTOR Imager 6000 (Meso Scale Discovery)
Laboratory: Central Biotechnology Services, Cardiff University, Cardiff, UK
Measurement Characteristics
| Characteristic | Value |
|---|---|
| Units | pg/mL |
| Measurement range | 13.0 – 80,000 pg/ml |
| Lower detection limit | 13.0 pg/ml |
| Assay CoV | 0.177 |
Collection Waves
| Biomarker | Wave 1 | Wave 2 | Wave 3 | Wave 4 | Wave 5 | Wave 6 |
|---|---|---|---|---|---|---|
| Insulin-like Growth Factor-1 | X | X |
Reference
- Junnila, R.K., List, E.O., Berryman, D.E., Murrey, J.W. and Kopchick, J.J. (2013) ‘The GH/IGF-1 axis in ageing and longevity’, Nature Reviews Endocrinology, 9(6), pp. 366–376. doi:10.1038/nrendo.2013.67.
Other References
- Vitale G, Pellegrino G, Vollery M, Hofland LJ. ROLE of IGF-1 System in the Modulation of Longevity: Controversies and New Insights From a Centenarians’ Perspective. Front Endocrinol (Lausanne). 2019 Feb 1;10:27. https://doi.org/10.3389/fendo.2019.00027
- Frater J, Lie D, Bartlett P, McGrath JJ. Insulin-like Growth Factor 1 (IGF-1) as a marker of cognitive decline in normal ageing: A review. Ageing Res Rev. 2018 Mar;42:14-27. https://doi.org/10.1016/j.arr.2017.12.002
- Wrigley S, Arafa D, Tropea D. Insulin-Like Growth Factor 1: At the Crossroads of Brain Development and Aging. Front Cell Neurosci. 2017 Feb 1;11:14. https://doi.org/10.3389/fncel.2017.00014
Overview
What is it? N-terminal pro B-type natriuretic peptide (NT-proBNP) is an inactive peptide released into the circulation alongside B-type natriuretic peptide (BNP) when cardiac muscle is subjected to increased wall stress and stretching. Circulating concentrations are widely used as a marker of cardiac stress and tend to increase with age and in conditions such as heart failure.
Research relevance: Can be used to investigate cardiac stress and cardiovascular health, including heart failure and other forms of cardiac dysfunction. In ageing research, NT-proBNP can also be examined in relation to cardiovascular disease, functional decline, mortality and cognitive outcomes.
Sample type: Frozen K2EDTA blood plasma
Sample Collection / Handling
Plasma isolated from 10 mL of fresh whole blood, maintained at 2–4°C for 24–48 hours after blood collection and subsequently frozen at −80°C.
Assay / Measurement
Method: Single-plex immunoassay using the Meso Scale Diagnostics (MSD) R-PLEX platform. Assays were conducted according to the manufacturer’s instructions, and NT-proBNP concentrations were calculated using MSD Discovery Workbench Software (v4.0).
Equipment / analyser: SECTOR Imager 6000 (Meso Scale Discovery)
Laboratory: Central Biotechnology Services, Cardiff University, Cardiff, UK
Measurement Characteristics
| Characteristic | Value |
|---|---|
| Units | pg/mL |
| Measurement range | 0.30 – 2,500 pg/ml |
| Lower detection limit | 0.30 pg/ml |
| Assay CoV | 0.064 |
Collection Waves
| Biomarker | Wave 1 | Wave 2 | Wave 3 | Wave 4 | Wave 5 | Wave 6 |
|---|---|---|---|---|---|---|
| N-terminal pro B-type Natriuretic Peptide | X | X |
Reference
- Mueller, C., McDonald, K., de Boer, R.A., Maisel, A., Cleland, J.G.F., Kozhuharov, N., Coats, A.J.S., Metra, M., Mebazaa, A., Ruschitzka, F., Lainscak, M., Filippatos, G., Seferovic, P.M., Meijers, W.C., Bayes-Genis, A., Mueller, T., Richards, M. and Januzzi, J.L. (2019) ‘Heart Failure Association of the European Society of Cardiology practical guidance on the use of natriuretic peptide concentrations’, European Journal of Heart Failure, 21(6), pp. 715–731. doi:10.1002/ejhf.1494.
Example TILDA Papers
- Nowak N, De Looze C, O’Halloran A, Kenny RA, Sexton DJ. The association between kidney function, cognitive function, and structural brain abnormalities in community-dwelling individuals aged 50+ is mediated by age and biomarkers of cardiovascular disease. Cardiovasc Res. 2023 Sep 5;119(11):2106-2116. https://doi.org/10.1093/cvr/cvad060
Other References
- Muscari A, Bianchi G, Forti P, Magalotti D, Pandolfi P, Zoli M; Pianoro Study Group. N-terminal pro B-type natriuretic peptide (NT-proBNP): a possible surrogate of biological age in the elderly people. Geroscience. 2021 Apr;43(2):845-857. doi: 10.1007/s11357-020-00249-2. Epub 2020 Aug 11. https://doi.org/10.1007/s11357-020-00249-2
- Welsh P, Campbell RT, Mooney L, Kimenai DM, Hayward C, Campbell A, Porteous D, Mills NL, Lang NN, Petrie MC, Januzzi JL, McMurray JJV, Sattar N. Reference Ranges for NT-proBNP (N-Terminal Pro-B-Type Natriuretic Peptide) and Risk Factors for Higher NT-proBNP Concentrations in a Large General Population Cohort. Circ Heart Fail. 2022 Oct;15(10):e009427 https://doi.org/10.1161/circheartfailure.121.009427
- Fabbian F, De Giorgi A, Pala M, Tiseo R, Portaluppi F. Elevated NT-proBNP levels should be interpreted in elderly patients presenting with dyspnea. Eur J Intern Med. 2011 Feb;22(1):108-11. https://doi.org/10.1016/j.ejim.2010.07.013
Overview
What is it? Metabolomics is the large-scale study of small molecules, or metabolites, produced through cellular and physiological processes. The metabolome reflects the combined influence of genetic, physiological, environmental and lifestyle factors and provides a molecular profile of an individual’s metabolic state.
Research relevance: Can be used to investigate metabolic pathways and molecular signatures associated with ageing, disease and environmental or lifestyle exposures. In ageing research, TILDA metabolomic data can support the identification of metabolic profiles associated with biological ageing, frailty, multimorbidity and other age-related outcomes, as well as the development of metabolomic ageing signatures.
Sample type: Frozen lithium-heparin blood plasma
Sample Collection / Handling
Plasma was isolated from 10 mL of fresh whole blood, maintained at 2–4°C for 24–48 hours after collection and subsequently frozen at −80°C. Archived plasma samples were analysed from Wave 1 (n=1,400) and Wave 3 (n=500).
Assay / Measurement
Method: Metabolomic profiling of 700+ lipid and small-molecule metabolites. Two dataset versions are available: NPC v1 includes NMR and UPLC-MS data (reversed-phase C8 lipids in positive and negative ionisation modes and HILIC in positive mode); NPC v2 includes reversed-phase C8 lipid and C18 small-molecule platforms in positive and negative ionisation modes. PeakPantheR was used to support metabolite quantification and long-term reference standards enabled normalisation of relative concentrations across datasets.
Equipment / analyser: NMR and UPLC-MS platforms; specific instrument models N/A
Laboratory: National Phenome Centre, Imperial College London, UK
Measurement Characteristics
| Characteristic | Value |
|---|---|
| Units | Relative metabolite concentrations / platform-dependent |
Collection Waves
| Biomarker | Wave 1 | Wave 2 | Wave 3 | Wave 4 | Wave 5 | Wave 6 |
|---|---|---|---|---|---|---|
| Metabolomics | X | X |
Reference
- Johnson, C.H., Ivanisevic, J. and Siuzdak, G. (2016) ‘Metabolomics: beyond biomarkers and towards mechanisms’, Nature Reviews Molecular Cell Biology, 17(7), pp. 451–459. doi:10.1038/nrm.2016.25.
Other References
- Robinson O, Lau CE. How do metabolic processes age: Evidence from human metabolomic studies. Curr Opin Chem Biol. 2023;76:102360. https://doi.org/10.1016/j.cbpa.2023.102360