Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
European Journal of Medical Research
Published in: European Journal of Medical Research 1/2023

Open Access 01-12-2023 | Obesity | Research

Association between adiposity and facial aging: results from a Mendelian randomization study

Authors: Meiqi Liu, Jingwei Feng

Published in: European Journal of Medical Research | Issue 1/2023

Login to get access

Abstract

Background

Skin, as a sociologically meaningful interface, has psychological implications different from other organs, particularly in the context of the global population aging. Growing evidence suggests that facial aging is associated with an increased risk of adiposity. Existing research, however, were observational, and while they may find some correlations, it is difficult to simply disentangle non-causal or reverse-causal links because these associations may be confounded or fail to accurately reflect true causative linkages.

Objectives

We conducted a 2-sample Mendelian randomization (MR) study to examine the potential effect of facial aging on the risk of broad obesity and its three major adiposity indicators, including body mass index (BMI), body fat percentage (BF%) and waist circumference (WC).

Methods

Genetic instruments from IEU OpenGWAS project, one of the largest available genome-wide association studies (GWAS) for facial aging (423,999 samples) were used to investigate the relation to broad obesity (32,858 cases, 65,839 controls). Using the inverse-variance weighted (IVW) technique, single nucleotide polymorphisms (SNPs) associated with adiposity indicators (BMI (461,460 samples), BF% (454,633 samples), and WC (462,166 samples)) were investigated in relationship to facial aging. Further sensitivity analyses were performed, including Mendelian randomization-Egger (MR-Egger), weighted median estimates, and leave-one-out analysis, to evaluate the consistency of the results and related potential issues in MR studies.

Results

We identified strong and significant correlations between adiposity and facial aging in the 17 broad obesity-associated SNPs (IVW estimate of odds ratio OR = 1.020, 95% CI 1.010–1.029, P = 7.303e − 05), 458 BMI-associated SNPs (IVW estimate of odds ratio OR = 1.047, 95% CI 1.0357–1.058, P = 1.154e − 16),for the 395 BF%-associated SNPs (OR = 1.056, 95%CI 1.040–1.072,P = 7.617e − 12), or for the 374 WC-associated SNPs (OR = 1.072, 95% CI 1057–1.087,P = 1.229e − 23). A range of complementary methodologies have been employed to evaluate horizontal pleiotropy and related potential caveats occurring in MR research.

Conclusions

Using Mendelian randomization as an alternative approach to investigate causality, we found a causal relationship between adiposity and facial aging, which was statistically strong and significant.
Appendix
Available only for authorised users
Literature
1.
2.
Von Bank H, Kirsh C, Simcox J. Aging adipose: Depot location dictates age-associated expansion and dysfunction. Ageing Res Rev. 2021;67: 101259.CrossRef
3.
Reyes-Farias M, Fos-Domenech J, Serra D, et al. White adipose tissue dysfunction in obesity and aging. Biochem Pharmacol. 2021;192: 114723.PubMedCrossRef
4.
Vijay J, Gauthier MF, Biswell RL, et al. Single-cell analysis of human adipose tissue identifies depot and disease specific cell types. Nat Metab. 2020;2(1):97–109.PubMedCrossRef
5.
Hirt PA, Castillo DE, Yosipovitch G, et al. Skin changes in the obese patient. J Am Acad Dermatol. 2019;81(5):1037–57.PubMedCrossRef
6.
Bourassa KJ, Moffitt TE, Ambler A, et al. Association of treatable health conditions during adolescence with accelerated aging at midlife. JAMA Pediatr. 2022;176(4):392–9.PubMedPubMedCentralCrossRef
7.
8.
Santos AL, Sinha S. Obesity and aging: molecular mechanisms and therapeutic approaches. Ageing Res Rev. 2021;67: 101268.PubMedCrossRef
9.
Wang L, Yi Z. Obesity paradox and aging: visceral adiposity index and all-cause mortality in older individuals: a prospective cohort study. Front Endocrinol. 2022;13: 975209.CrossRef
10.
Yosipovitch G, Devore A, Dawn A. Obesity and the skin: skin physiology and skin manifestations of obesity. J Am Acad Dermatol. 2007;56(6):901–16.PubMedCrossRef
11.
Valente DS, Braga Da Silva J, Cora Mottin C, et al. Influence of massive weight loss on the perception of facial age: the facial age perceptions cohort. Plast Reconstr Surg. 2018;142(4):481e–8e.PubMedCrossRef
12.
Davey Smith G, Phillips AN. Correlation without a cause: an epidemiological odyssey. Int J Epidemiol. 2020;49(1):4–14.PubMedCrossRef
13.
Hu X, Zhao J, Lin Z, et al. Mendelian randomization for causal inference accounting for pleiotropy and sample structure using genome-wide summary statistics. Proc Natl Acad Sci USA. 2022;119(28): e2106858119.PubMedPubMedCentralCrossRef
14.
Burgess S, Foley CN, Zuber V. Inferring causal relationships between risk factors and outcomes from genome-wide association study data. Annu Rev Genom Hum Genet. 2018;19:303–27.CrossRef
15.
Davey Smith G, Holmes MV, Davies NM, et al. Mendel’s laws, Mendelian randomization and causal inference in observational data: substantive and nomenclatural issues. Eur J Epidemiol. 2020;35(2):99–111.PubMedPubMedCentralCrossRef
16.
17.
Lu Y, Day FR, Gustafsson S, et al. New loci for body fat percentage reveal link between adiposity and cardiometabolic disease risk. Nat Commun. 2016;7:10495.PubMedPubMedCentralCrossRef
18.
Lyon MS, Andrews SJ, Elsworth B, et al. The variant call format provides efficient and robust storage of GWAS summary statistics. Genome Biol. 2021;22(1):32.PubMedPubMedCentralCrossRef
19.
20.
Ruth Mitchell E, BL, Mitchell, R, Raistrick, CA, Paternoster, L, Hemani, G, Gaunt, TR. MRC IEU UK Biobank GWAS pipeline version 2 [DS]. 2019,
21.
Zhan Y, Hagg S. Association between genetically predicted telomere length and facial skin aging in the UK biobank: a mendelian randomization study. Geroscience. 2021;43(3):1519–25.PubMedCrossRef
22.
Jiang L, Zheng Z, Fang H, et al. A generalized linear mixed model association tool for biobank-scale data. Nat Genet. 2021;53(11):1616–21.PubMedCrossRef
23.
Sekula P, Del Greco MF, Pattaro C, et al. Mendelian randomization as an approach to assess causality using observational data. J Am Soc Nephrol. 2016;27(11):3253–65.PubMedPubMedCentralCrossRef
24.
Hartwig FP, Borges MC, Horta BL, et al. Inflammatory biomarkers and risk of schizophrenia: a 2-sample mendelian randomization study. JAMA Psychiat. 2017;74(12):1226–33.CrossRef
25.
Burgess S, Scott RA, Timpson NJ, et al. Using published data in mendelian randomization: a blueprint for efficient identification of causal risk factors. Eur J Epidemiol. 2015;30(7):543–52.PubMedPubMedCentralCrossRef
26.
Bowden J, Davey Smith G, Haycock PC, et al. Consistent estimation in mendelian randomization with some invalid instruments using a weighted median estimator. Genet Epidemiol. 2016;40(4):304–14.PubMedPubMedCentralCrossRef
27.
Bowden J, Davey Smith G, Burgess S. Mendelian randomization with invalid instruments: effect estimation and bias detection through egger regression. Int J Epidemiol. 2015;44(2):512–25.PubMedPubMedCentralCrossRef
28.
Hartwig FP, Davey Smith G, Bowden J. Robust inference in summary data mendelian randomization via the zero modal pleiotropy assumption. Int J Epidemiol. 2017;46(6):1985–98.PubMedPubMedCentralCrossRef
29.
30.
31.
32.
Wang HY, Chang SC, Lin WY, et al. Machine learning-based method for obesity risk evaluation using single-nucleotide polymorphisms derived from next-generation sequencing. J Comput Biol. 2018;25(12):1347–60.PubMedCrossRef
33.
Zou X, Wang L, Xiao L, et al. Deciphering the irregular risk of stroke increased by obesity classes: a stratified mendelian randomization study. Front Endocrinol. 2021;12: 750999.CrossRef
34.
Bell CG, Gao F, Yuan W, et al. Obligatory and facilitative allelic variation in the DNA methylome within common disease-associated loci. Nat Commun. 2018;9(1):8.PubMedPubMedCentralCrossRef
35.
36.
Nanda V, Gutman B, Bar E, et al. Quantitative analysis of 3-dimensional facial soft tissue photographic images: technical methods and clinical application. Prog Orthod. 2015;16:21.PubMedPubMedCentralCrossRef
37.
Dykiert D, Bates TC, Gow AJ, et al. Predicting mortality from human faces. Psychosom Med. 2012;74(6):560–6.PubMedCrossRef
38.
Tomlinson DJ, Erskine RM, Morse CI, et al. The combined effects of obesity and ageing on skeletal muscle function and tendon properties in vivo in men. Endocrine. 2021;72(2):411–22.PubMedPubMedCentralCrossRef
39.
Rexbye H, Petersen I, Johansens M, et al. Influence of environmental factors on facial ageing. Age Ageing. 2006;35(2):110–5.PubMedCrossRef
40.
Shook BA, Wasko RR, Mano O, et al. Dermal adipocyte lipolysis and myofibroblast conversion are required for efficient skin repair. Cell Stem Cell. 2020;26(6):880–95.PubMedPubMedCentralCrossRef
41.
Crowley JS, Kream E, Fabi S, et al. Facial rejuvenation with fat grafting and fillers. Aesthet Surg J. 2021;41(Suppl 1):S31–8.PubMedCrossRef
42.
43.
Yan B, Yang J, Zhao B, et al. Causal effect of visceral adipose tissue accumulation on the human longevity: a mendelian randomization study. Front Endocrinol. 2021;12: 722187.CrossRef
44.
Rogers NH, Landa A, Park S, et al. Aging leads to a programmed loss of brown adipocytes in murine subcutaneous white adipose tissue. Aging Cell. 2012;11(6):1074–83.PubMedCrossRef
45.
Marcangeli V, Youssef L, Dulac M, et al. Impact of high-intensity interval training with or without l-citrulline on physical performance, skeletal muscle, and adipose tissue in obese older adults. J Cachexia Sarcopenia Muscle. 2022;13(3):1526–40.PubMedPubMedCentralCrossRef
46.
47.
Zhou Q, Wan Q, Jiang Y, et al. A landscape of murine long non-coding RNAs reveals the leading transcriptome alterations in adipose tissue during aging. Cell Rep. 2020;31(8): 107694.PubMedPubMedCentralCrossRef
48.
Trim WV, Walhin JP, Koumanov F, et al. Divergent immunometabolic changes in adipose tissue and skeletal muscle with ageing in healthy humans. J Physiol. 2022;600(4):921–47.PubMedCrossRef
49.
Srivastava A, Barth E, Ermolaeva MA, et al. Tissue-specific gene expression changes are associated with aging in mice. Genom Proteom Bioinform. 2020;18(4):430–42.CrossRef
50.
Millard LAC, Munafo MR, Tilling K, et al. MR-pheWAS with stratification and interaction: searching for the causal effects of smoking heaviness identified an effect on facial aging. PLoS Genet. 2019;15(10): e1008353.PubMedPubMedCentralCrossRef
51.
Topiwala A, Taschler B, Ebmeier KP, et al. Alcohol consumption and telomere length: mendelian randomization clarifies alcohol’s effects. Mol Psychiatry. 2022;27(10):4001–8.PubMedPubMedCentralCrossRef
Metadata
Title
Association between adiposity and facial aging: results from a Mendelian randomization study
Authors
Meiqi Liu
Jingwei Feng
Publication date
01-12-2023
Publisher
BioMed Central
Keywords
Obesity
Obesity
Published in
European Journal of Medical Research / Issue 1/2023
Electronic ISSN: 2047-783X
DOI
https://doi.org/10.1186/s40001-023-01236-x

Other articles of this Issue 1/2023

European Journal of Medical Research 1/2023 Go to the issue

Research

Remimazolam tosylate's long-term sedative properties in ICU patients on mechanical ventilation: effectiveness and safety

Research

Acute subdural haematoma exacerbates cerebral blood flow disorder and promotes the development of intraoperative brain bulge in patients with severe traumatic brain injury

Review

Artificial intelligence in cardiovascular diseases: diagnostic and therapeutic perspectives

Research

Percutaneous coronary intervention vs. coronary artery bypass grafting in emergency and non-emergency unprotected left-main revascularization

Research

Identifying effective diagnostic biomarkers for childhood cerebral malaria in Africa integrating coexpression analysis with machine learning algorithm

Research

Serum growth differentiation factor-15 (GDF-15) is a biomarker of cardiac manifestations in children with COVID-19