Commentary: Life course epidemiology: the past two decades and future directions
Open accessAbstract
Life course epidemiology has the great potential to help us understand why and how we age. Ultimately, the goal of such research is to identify the critical time points where interventions could ameliorate the disabling consequences of ageing. Epidemiological studies have assessed risk for disability in late life or have focused on longevity. It is now clear that we need to look back to earlier points in life to understand the origins of these important outcomes. The review by Ben-Shlomo, Cooper and Kuh1 provides an important perspective on how life course and ageing research are linked and can inform each other. Ageing is most easily recognized in the very old with a stereotypical pattern of slowing gait, greying hair and loss of function in many organ systems. For being so universally recognizable, it is perhaps surprising that ageing is so difficult to measure. Genetic and environmental manipulations such as caloric restriction clearly promote longevity in animal models.2 In these models, researchers are advocating for more emphasis on measuring health span and adopting measures of the signs of ageing such as motility or mobility.3 In humans, measures of physical and cognitive performance are often used to define the degree or rate of ageing.4 Changes in these domains are often only apparent very late in life.5 This lack of sensitivity results in a ‘ceiling effect’, where we cannot detect better than usual function. Since most younger-old and middle-aged adults function in this usual range, it is not possible to use basic measures of physical and cognitive function to understand ageing earlier in life. Biomarkers of the process of ageing have long been sought, but no single measure has been found that can compete with chronological age itself in prediction mortality or health span.6 Measures that are informative about the ageing process across the lifespan are needed to advance life course epidemiology to study ageing. One important question for life course epidemiology of ageing is: ‘When does ageing begin’? This would reveal opportunities for delaying its start or maximizing development before its onset. Some would argue that ageing begins at conception, or even before conception,7 in that measures linked to ageing like telomere length8 and mitochondrial heteroplasmy9 are inherited. Certainly there is much to learn from the field of the developmental origins of health and disease (DOHaD). Current studies are limited in design by the selection of measures chosen for purposes other than ageing, yet are currently most valuable to address questions of risk for disease, disability and death from the vantage point of early life determinants. Looking further down the line, others would define the start of ageing as the period starting after the achievement of peak development. After this point, there can be stability or the earliest signs of decline. Endurance in physical activity, particularly maximal oxygen consumption, is well known to begin to decline around age 40.10 This is recognized in the age of peak performance of marathon runners as well as in physiological studies that assess volume of oxygen uptake (VO2) serially. Many epidemiological studies of ageing have started only at age 65 or 70, and thus have missed the opportunity to understand the roles of peak development and early decline as risk factors for future function and ageing. Conversely, many of the ongoing studies in middle age or younger have not included age-sensitive measures. Promising measures include VO2 max,10 bone density11 and muscle strength,12 all of which have been shown to have age-related declines well before age 65. The variable course of ageing is an important challenge in doing life course research. Variability itself is prognostic for poor health outcomes.13 Increasing the frequency of assessment can aid in understanding this. Perhaps the field could borrow the approach of using frequent ’burst’ assessments from psychology14 which has been shown to capture response to stress and recovery. Potentially, the process of ageing might be revealed earlier by the use of tests of vulnerability or resilience to stressors. Such an approach is being adopted in the development of drugs in model organisms. Testing endurance with VO2 max might be considered a stress test of capacity to respond to a stressor, reflecting vulnerability or resilience due to ageing. As noted by Ben-Shlomo, Copper and Kuh,1 the assessment of response to stressors can be considered in the context of the sensitive periods in the life course. Ageing and age-related chronic disease are intrinsically linked in that age is a risk factor for disease and multimorbidity is a major contributor to age-related decline. It is not certain whether these can be disentangled in longitudinal studies. The previous emphasis of ageing studies on disease outcomes has considered many diseases such as osteoporosis and cardiovascular disease (CVD) individually, limiting our ability to
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
High levels of age-associated pro-inflammatory markers are detected in most older individuals even without risk factors and clinically active diseases.
“High levels of age-associated pro-inflammatory markers are detected in the majority of older individuals, even in the absence of risk factors and clinically active diseases3,5–7.”
From Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty (2018) · cites this paper as [6]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Effect of In Utero and Early-Life Conditions on Adult Health and Disease
Gluckman, P. D., Hanson, M. A., Cooper, C., & Thornburg, K. L. (2008) · New England Journal of Medicine · doi:10.1056/nejmra0708473 · Cited by 3,898 · see citing works
Extending Healthy Life Span—From Yeast to Humans
Fontana, L., Partridge, L., & Longo, V. D. (2010) · Science · doi:10.1126/science.1172539 · Cited by 3,023 · see citing works
Collins, G. S., Reitsma, J. B., Altman, D. G., & Moons, K. (2015) · BMC Medicine · doi:10.1186/s12916-014-0241-z · Cited by 1,927 · see citing works
Accelerated longitudinal decline of aerobic capacity in healthy older adults
Fleg, J. L., Morrell, C. H., Bos, A. G., Brant, L. J., Talbot, L. A., Wright, J. G., & Lakatta, E. G. (2005) · Circulation · doi:10.1161/circulationaha.105.545459 · Cited by 970 · see citing works
Levine, M. E. (2012) · The Journals of Gerontology Series A · doi:10.1093/gerona/gls233 · Cited by 897 · see citing works
Age-Associated Loss of Power and Strength in the Upper Extremities in Women and Men
Metter, E. J., Conwit, R., Tobin, J., & Fozard, J. L. (1997) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/52a.5.b267 · Cited by 592 · see citing works
Broer, L., Codd, V., Nyholt, D. R., Deelen, J., Mangino, M., Willemsen, G., Albrecht, E., Amin, N., Beekman, M., de Geus, E. J. C., et al. (2013) · European Journal of Human Genetics · doi:10.1038/ejhg.2012.303 · Cited by 450 · see citing works
The last two decades of life course epidemiology, and its relevance for research on ageing
Ben‐Shlomo, Y., Cooper, R., & Kuh, D. J. (2016) · International Journal of Epidemiology · doi:10.1093/ije/dyw096 · Cited by 270 · see citing works
A proposed panel of biomarkers of healthy ageing
Lara, J., Cooper, R., Nissan, J. J., Ginty, A. T., Khaw, K., Deary, I. J., Lord, J. M., Kuh, D. J., & Mathers, J. C. (2015) · BMC Medicine · doi:10.1186/s12916-015-0470-9 · Cited by 225 · see citing works
Patterns of Birth Cohort–Specific Smoking Histories, 1965–2009
Holford, T. R., Levy, D. T., McKay, L. A., Clarke, L. D., Racine, B., Meza, R., Land, S. R., Jeon, J., & Feuer, E. J. (2014) · American Journal of Preventive Medicine · doi:10.1016/j.amepre.2013.10.022 · Cited by 199 · see citing works
Arnold, A., Newman, A. B., Cushman, M., Ding, J., & Kritchevsky, S. B. (2009) · The Journals of Gerontology Series A · doi:10.1093/gerona/glp050 · Cited by 126 · see citing works
Self-citationBattery of behavioral tests in mice that models age-associated changes in human motor function
Justice, J. N., Carter, C. S., Beck, H. J., Gioscia‐Ryan, R. A., McQueen, M. B., Enoka, R. M., & Seals, D. R. (2013) · AGE · doi:10.1007/s11357-013-9589-9 · Cited by 125 · see citing works
Long‐Term Function in an Older Cohort—The Cardiovascular Health Study All Stars Study
Newman, A. B., Arnold, A. M., Sachs, M. C., Ives, D. G., Cushman, M., Strotmeyer, E. S., Ding, J., Kritchevsky, S. B., Chaves, P. H. M., Fried, L. P., et al. (2009) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.2008.02152.x · Cited by 80 · see citing works
Self-citationHereditary mtDNA Heteroplasmy: A Baseline for Aging?
Keogh, M. J., & Chinnery, P. F. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.09.015 · Cited by 46 · see citing works
Serum 25 Hydroxyvitamin D, Bone Mineral Density and Fracture Risk Across the Menopause
Cauley, J. A., Greendale, G. A., Ruppert, K. M., Lian, Y., Randolph, J. F., Lo, J. C.-M., Burnett‐Bowie, S. M., & Finkelstein, J. S. (2015) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2014-4367 · Cited by 44 · see citing works
Whitehead, B. R., & Bergeman, C. S. (2013) · The Journals of Gerontology Series B · doi:10.1093/geronb/gbt019 · Cited by 34 · see citing works
Victor, C. R. (2005) · Cambridge University Press eBooks · doi:10.1017/cbo9780511610714.009 · Cited by 19 · see citing works
Flagged first, then by citations
1 of the 18 references couldn’t be matched to a known paper.
Research works printed but not linked: 12
- Cooper R, Kuh D, Cooper C et al.; FALCon and HALCyon Study Teams. Objective measures of physical capability and sub- sequent health: a systematic review. Age Ageing 2011;40:14-23.
- Cooper R, Kuh D, Hardy R; Mortality Review Group, FALCon and HALCyon Study Teams. Objectively measured physical cap- ability levels and mortality: systematic review and meta-analysis. BMJ 2010;341:c4467.
- Dodds RM, Syddall HE, Cooper R et al. Grip strength across the life course: normative data from twelve British studies. PLoS One 2014;9:e113637.
- Inskip HM, Godfrey KM, Robinson SM, Law CM, Barker DJ, Cooper C ; SWS Study Group. Cohort profile: The Southampton Women's Survey. Int J Epidemiol 2006;35:42-48.
- Simmonds SJ, Syddall HE, Westbury LD, Dodds RM, Cooper C, Sayer AA. Grip strength among community-dwelling older people predicts hospital admission during the following decade. Age Ageing 2015;44:954-59.
- Kerr A, Syddall HE, Cooper C, Turner GF, Briggs RS, Sayer AA. Does admission grip strength predict length of stay in hospital- ised older patients? Age Ageing 2006;35:82-84.
- Gill TM, Gahbauer EA, Han L, Allore HG. Trajectories of dis- ability in the last year of life. N Engl J Med 2010;362:1173-80.
- Gill TM, Hardy SE, Williams CS. Underestimation of disability in community-living older persons. J Am Geriatr Soc 2002;50: 1492-97.
- Gill TM, Kurland B. The burden and patterns of disability in activities of daily living among community-living older persons. J Gerontol A Biol Sci Med Sci 2003;58:70-75.
- Gill TM, Williams CS, Mendes de Leon CF, Tinetti ME. The role of change in physical performance in determining risk for depend- ence in activities of daily living among nondisabled community- living elderly persons. J Clin Epidemiol 1997;50:765-72.
- Gill TM, Baker DI, Gottschalk M, Peduzzi PN, Allore H, Byers A. A program to prevent functional decline in physically frail, elderly persons who live at home. N Engl J Med 2002;347:1068-74.
- Denison HJ, Syddall HE, Dodds R et al. The effects of aerobic exer- cise on sarcopenia and physical performance among community dwelling older people from the Hertfordshire Cohort Study: a rand- omised controlled trial. Age Ageing 2013;42(Suppl 2): ii26-ii27. International Journal of Epidemiology, 2016, 1013-1015 doi: 10.1093/ije/dyw102 References
Cited by
Sorted by citations
Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty
Ferrucci, L., & Fabbri, E. (2018) · Nature Reviews Cardiology · doi:10.1038/s41569-018-0064-2 · Cited by 3,690 · see citing works
The last two decades of life course epidemiology, and its relevance for research on ageing
Ben‐Shlomo, Y., Cooper, R., & Kuh, D. J. (2016) · International Journal of Epidemiology · doi:10.1093/ije/dyw096 · Cited by 270 · see citing works
Peripheral immune system in aging and Alzheimer’s disease
Cao, W., & Zheng, H. (2018) · Molecular Neurodegeneration · doi:10.1186/s13024-018-0284-2 · Cited by 214 · see citing works
Liu, C. H., Abrams, N., Carrick, D. M., Chander, P., Dwyer, J. T., Hamlet, M. R. J., Macchiarini, F., PrabhuDas, M., Shen, G. L., Tandon, P., et al. (2017) · Nature Immunology · doi:10.1038/ni.3828 · Cited by 132 · see citing works
Peripheral and central neuroimmune mechanisms in Alzheimer’s disease pathogenesis
Zhang, S., Gao, Y., Zhao, Y., Huang, T. Y., Zheng, Q., & Wang, X. (2025) · Molecular Neurodegeneration · doi:10.1186/s13024-025-00812-5 · Cited by 78 · see citing works
Role of Microgliosis and NLRP3 Inflammasome in Parkinson’s Disease Pathogenesis and Therapy
de Araújo, F. M., Cuenca‐Bermejo, L., Fernández‐Villalba, E., Costa, S. L., da Silva, V. D. A., & Herrero, M. T. (2021) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-020-01027-6 · Cited by 61 · see citing works
Westbury, L. D., Syddall, H. E., Fuggle, N. R., Dennison, E. M., Cauley, J. A., Shiroma, E. J., Fielding, R. A., Newman, A. B., & Cooper, C. C. (2020) · Calcified Tissue International · doi:10.1007/s00223-020-00679-2 · Cited by 47 · see citing works
Self-citationOld plasma dilution reduces human biological age: a clinical study
Kim, D., KIPROV, D. D., Luellen, C., Lieb, M., Liu, C., Watanabe, E., Mei, X., Casaletto, K. B., Kramer, J. H., Conboy, M. J., et al. (2022) · GeroScience · doi:10.1007/s11357-022-00645-w · Cited by 43 · see citing works
Koivunen, K., Sillanpää, E., Munukka, M., Portegijs, E., & Rantanen, T. (2020) · The Journals of Gerontology Series A · doi:10.1093/gerona/glaa224 · Cited by 43 · see citing works
Syddall, H. E., Westbury, L. D., Shaw, S., Dennison, E. M., Cooper, C. C., & Galé, C. R. (2017) · Calcified Tissue International · doi:10.1007/s00223-017-0337-5 · Cited by 34 · see citing works
Hvid, L. G., Feys, P., Baert, I., Kalron, A., & Dalgas, U. (2020) · Neurorehabilitation and neural repair · doi:10.1177/1545968320907074 · Cited by 32 · see citing works
Pace of Aging analysis of healthspan and lifespan in older adults in the US and UK
Balachandran, A., Pei, H., Shi, Y., Beard, J., Caspi, A., Cohen, A. A., Domingue, B. W., Indik, C. E., Ferrucci, L., Furuya, A., et al. (2025) · Nature Aging · doi:10.1038/s43587-025-00866-6 · Cited by 22 · see citing works
Schubert, C. R., Paulsen, A. J., Nondahl, D. M., Dalton, D. S., Fischer, M., Klein, R., Klein, R., Tweed, T. S., & Cruickshanks, K. J. (2018) · JAMA Otolaryngology–Head & Neck Surgery · doi:10.1001/jamaoto.2018.0041 · Cited by 15 · see citing works
Zheng, J.-B., Liang, Q.-F., Li, J.-H., Zhang, S., Yu, X.-H., Zhao, J., Liang, G.-Q., Shi, H., Zhou, W., & Zhu, Q. (2019) · The Journal of Sexual Medicine · doi:10.1016/j.jsxm.2019.07.017 · Cited by 9 · see citing works
Fermín‐Martínez, C. A., Ramírez‐García, D., Antonio‐Villa, N. E., Perezalonso-Espinosa, J., Aguilar-Ramirez, D. J., García‐Peña, C., Gutiérrez‐Robledo, L. M., Seiglie, J. A., & Bello‐Chavolla, O. Y. (2025) · npj Aging · doi:10.1038/s41514-025-00232-1 · Cited by 5 · see citing works
Jones, P. M., Minton, J., & Bell, A. (2022) · Quality & Quantity: International Journal of Methodology · doi:10.1007/s11135-022-01498-3 · Cited by 4 · see citing works
Associations between serum cystatin C and fall reports in an Elderly population
Han, J., Wang, R., Bai, L., Liu, Y., Liao, M., Zhang, L., Liu, L., & Qi, B. (2024) · Scientific Reports · doi:10.1038/s41598-024-77138-7 · Cited by 3 · see citing works
An inflammatory clock for healthy aging
Iruela‐Arispe, M. L. (2021) · Nature Aging · doi:10.1038/s43587-021-00085-9 · Cited by 2 · see citing works
Benton, M. J., & Hutchins, A. M. (2024) · BMC Women s Health · doi:10.1186/s12905-024-03085-0 · Cited by 2 · see citing works
Jones, P. M., Minton, J., & Bell, A. (2017) · doi:10.31219/osf.io/4f7jr · Cited by 1 · see citing works
- Authors
- Newman, A. B.
- Affiliations
- University of Pittsburgh (US)
- Corresponding author
- Newman, Anne B
- ORCID
- Newman, Anne B
- Venue
- International Journal of Epidemiology
- Publisher
- Oxford University Press (OUP)
- Published
- 2016-08-01
- Volume
- 45
- Issue
- 4
- Pages
- 1013-1015
- ISSN
- 0300-5771 (ISSN-L)
- 1464-3685
- PMC
- PMC5841775
- OpenAlex
- W2531561637
- Cited by
- 20
- References
- 18
- Citations by year
- 2025: 3 · 2024: 2 · 2022: 2 · 2021: 2 · 2020: 3 · 2019: 1 · 2018: 3 · 2017: 3 · 2016: 1
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- public-domain
- Locations
- International Journal of Epidemiology (publishedVersion, public-domain)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- National Institute of Aging (NIA) (R01 AG023629)
- Exceptional Survival: Trajectories to Functional Aging (P30 AG024827)
- Topics
- Social Sciences › Health › Health disparities and outcomes
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Aging, Health, and Disability
- Social Sciences › Psychology › Neuropsychology and Physiological Psychology › Aging and Gerontology Research
- Keywords
- life course epidemiology, aging, healthspan, aging biomarkers, developmental origins of health and disease, early life factors, telomere length, mitochondrial heteroplasmy, longevity, middle-aged and older adults, mortality risk
- MeSH terms
- Forecasting, Humans
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
