A framework of biomarkers for visual system aging: a consensus statement by the Aging Biomarker Consortium

Aging Biomarker Consortium; Chao Ma; Boxin Geng; Yangqing Zhang; Shan Li; Ruiyang Li; Wenben Chen; Si Wang; Weiqi Zhang; Jing Qu; Yun Feng; Qingfeng Liang; Kangxin Jin; Yonghao Gu; Wenru Su; Xuxiang Zhang; Wenjuan Zhuang; Jihong Wu; Zhaoyang Wang; Shengping Hou; Jiaxu Hong; Honghua Yu; Biao Yan; Mingguang He; Fan Lv; Guang-hui Liu; Gang Pei; Qingjiong Zhang; Tian Xue; Zi-Bing Jin

doi:10.1093/lifemedi/lnaf023

Life Medicine ›› 2025, Vol. 4 ›› Issue (4) : lnaf023 DOI: 10.1093/lifemedi/lnaf023

Forum

A framework of biomarkers for visual system aging: a consensus statement by the Aging Biomarker Consortium

Aging Biomarker Consortium
, Chao Ma ¹
, Boxin Geng ¹
, Yangqing Zhang ¹^,²
, Shan Li ¹
, Ruiyang Li ³
, Wenben Chen ³
, Si Wang ⁴
, Weiqi Zhang ⁵^,⁶
, Jing Qu ⁷^,⁸^,⁹^,¹⁰
, Yun Feng ¹¹
, Qingfeng Liang ¹
, Kangxin Jin ¹
, Yonghao Gu ¹²
, Wenru Su ¹³
, Xuxiang Zhang ¹⁴
, Wenjuan Zhuang ¹⁵
, Jihong Wu ¹⁶^,¹⁷^,¹⁸^,¹⁹
, Zhaoyang Wang ²⁰
, Shengping Hou ¹
, Jiaxu Hong ²¹
, Honghua Yu ²²
, Biao Yan ²³
, Mingguang He ²⁴
, Fan Lv ²⁵^,²⁶
, Guang-hui Liu ²⁷^,²⁸^,²⁹
, Gang Pei ³⁰
, Qingjiong Zhang ³¹
, Tian Xue ³²
, Zi-Bing Jin ¹

Author information +

¹. Beijing Tongren Hospital, Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Capital Medical University, Beijing Key Laboratory of Ophthalmology & Visual Science, Beijing 100005, China

². School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China

³. State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Vision Science, Guangdong Provincial Clinical Research Center for Ocular Diseases, Guangzhou 510060, China

⁴. Advanced Innovation Center for Human Brain Protection, National Clinical Research Center for Geriatric Disorders, Aging Translational Medicine Center, Beijing Municipal Geriatric Medical Research Center, Beijing Key Laboratory of Environment and Aging, Xuanwu Hospital Capital Medical University, Beijing 100053, China

⁵. China National Center for Bioinformation and Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China

⁶. Beijing Institute of Genomics, University of Chinese Academy of Sciences, Beijing 101408, China

⁷. State Key Laboratory of Organ Regeneration and Reconstruction, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China

⁸. Beijing Institute for Stem Cell and Regenerative Medicine, Beijing 100101, China

⁹. Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China

¹⁰. University of Chinese Academy of Sciences, Beijing 100049, China

¹¹. Department of Ophthalmology, Peking University First Hospital, Beijing 100034, China

¹². Department of Ophthalmology, First Affiliated Hospital of University of Science and Technology of China, Hefei 230001, China

¹³. Department of Ophthalmology, State Key Laboratory of Visual Science Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China

¹⁴. Department of Ophthalmology, Xuanwu Hospital, Capital Medical University, Beijing 100037, China

¹⁵. Department of Ophthalmology, People's Hospital of Ningxia Hui Autonomous Region, Yinchuan 750011, China

¹⁶. Department of Opthalmology, Eye and ENT Hospital, Fudan University, Shanghai 200031, China

¹⁷. Shanghai Key Laboratory of Visual Impairment and Restoration, Science and Technology Commission of Shanghai Municipality, Shanghai 200031, China

¹⁸. Key Laboratory of Myopia and Related Eye Diseases, NHC, Shanghai 200031, China

¹⁹. Key Laboratory of Myopia and Related Eye Diseases, Chinese Academy of Medical Sciences, Shanghai 200031, China

²⁰. Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing 100005, China

²¹. Department of Ophthalmology, Eye & ENT Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai 200031, China

²². Guangdong Eye Institute, Department of Ophthalmology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, China

²³. Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China

²⁴. The Hong Kong Polytechnic University, Hong Kong 999077, China

²⁵. State Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital, Wenzhou Medical University, Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou 325041, China

²⁶. Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou 325001, China

²⁷. State Key Laboratory of Organ Regeneration and Reconstruction, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China

²⁸. University of Chinese Academy of Sciences, Beijing 100049, China

²⁹. Beijing Institute for Stem Cell and Regenerative Medicine, Beijing 100101, China

³⁰. Collaborative Innovation Center for Brain Science, School of Life Science and Technology, Tongji University, Shanghai 200092, China

³¹. State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou 510060, China

³². Department of Ophthalmology, The First Affiliated Hospital of USTC, State Key Laboratory of Eye Health, School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, China

liruiyang@gzzoc.com (R.L.)

weberchan@foxmail.com (W.C.)

wangsi@xwh.ccmu.edu.cn (S.W.)

zhangwq@big.ac.cn (W.Z.)

qujing@ioz.ac.cn (J.Q.)

fengyun@bjmu.edu.cn (Y.F.)

liangqingfeng@ccmu.edu.cn (Q.L.)

jinkx@mail.ccmu.edu.cn (K.J.)

Guyh@ustc.edu.cn (Y.G.)

suwenru@sjtu.edu.cn (W.S.)

zhang_xuxiang@hotmail.com (X.Z.)

zh_wenj@163.com (W.Z.)

jihongwu@fudan.edu.cn (J.W.)

zhaokekewzy@hotmail.com (Z.W.)

sphou828@163.com (S.H.)

Jiaxu.hong@fdeent.org (J.H.)

yuhonghua@gdph.org.cn (H.Y.)

yanbiao@sjtu.edu.cn (B.Y.)

mingguang.he@polyu.edu.hk (M.H.)

lufan62@mail.eye.ac.cn (F.L.)

ghliu@ioz.ac.cn (G.-H.L.)

peigang@tongji.edu.cn (G.P.)

zhangqji@mail.sysu.edu.cn (Q.Z.)

xuetian@ustc.edu.cn (T.X.)

jinzb502@ccmu.edu.cn (Z.-B.J.)

Show less

History +

PDF (499KB)

Abstract

The visual system is essential for human perception, converting light signals into electrical impulses and transmitting them to the brain to process environmental information. As individuals age, their physiological functions gradually decline, leading to age-related vision impairment that significantly impacts the quality of life in elderly individuals. China is home to the world's largest aging population and faces significant challenges in combating visual system aging through effective treatments and interventions. In response to this challenge, the Aging Biomarker Consortium (ABC) of China has developed a consensus statement on biomarkers of visual system aging by integrating cutting-edge global research and synthesizing evidence-based medicine with clinical expertise. This consensus provides a multi-dimensional evaluation framework encompassing functional, morphological, and molecular biomarkers. Validated biomarkers for each domain are recommended not only to facilitate the early detection of vision changes but also to provide insights into the progression of age-related ocular diseases. By advancing this initiative, ABC aims to revolutionize visual health management in aging societies, ultimately improving outcomes for elderly populations in China and globally.

Cite this article

Download citation ▾

Aging Biomarker Consortium, Chao Ma, Boxin Geng, Yangqing Zhang, Shan Li, Ruiyang Li, Wenben Chen, Si Wang, Weiqi Zhang, Jing Qu, Yun Feng, Qingfeng Liang, Kangxin Jin, Yonghao Gu, Wenru Su, Xuxiang Zhang, Wenjuan Zhuang, Jihong Wu, Zhaoyang Wang, Shengping Hou, Jiaxu Hong, Honghua Yu, Biao Yan, Mingguang He, Fan Lv, Guang-hui Liu, Gang Pei, Qingjiong Zhang, Tian Xue, Zi-Bing Jin. A framework of biomarkers for visual system aging: a consensus statement by the Aging Biomarker Consortium. Life Medicine, 2025, 4(4): lnaf023 DOI:10.1093/lifemedi/lnaf023

登录浏览全文

4963

注册一个新账户忘记密码

References

Publishing order | Descend order by publishing year | Descend order by cited within

[1]	Calkins DJ. Age-related changes in the visual pathways:blame it on the axon. Invest Ophthalmol Vis Sci 2013; 54: ORSF37- 41.

[2]	Shang X, Zhu Z, Wang W, et al. The association between vision impairment and incidence of dementia and cognitive impairment:a systematic review and meta-analysis. Ophthalmology 2021; 128: 1135- 49.

[3]	Zhang X, Shang X, Seth I, et al. Association of visual health with depressive symptoms and brain imaging phenotypes among middle-aged and older adults. JAMA Netw Open 2022; 5: e2235017.

[4]	Sousa-Uva M, Head SJ, Thielmann M, et al. Methodology manual for european association for cardio-thoracic surgery (EACTS) clinical guidelines. Eur J Cardiothorac Surg 2015; 48: 809- 16.

[5]	Fleckenstein M, Keenan TDL, Guymer RH, et al. Age-related macular degeneration. Nat Rev Dis Primers 2021; 7: 31.

[6]	Lam D, Rao SK, Ratra V, et al. Cataract. Nat Rev Dis Primers 2015; 1: 15014.

[7]	Zhu X, Xu M, Portal C, et al. Identification of meibomian gland stem cell populations and mechanisms of aging. Nat Commun 2025; 16: 1663.

[8]	Hwang HS, Parfitt GJ, Brown DJ, et al. Meibocyte differentiation and renewal:Insights into novel mechanisms of meibomian gland dysfunction (MGD). Exp Eye Res 2017; 163: 37- 45.

[9]

Chinese Branch of the Asian Dry Eye Society; Ocular Surface and Tear Film Diseases Group of Ophthalmology Committee of Cross-Straits-Medicine-Exchange-Association; Ocular Surface and Dry Eye Group of Chinese Ophthalmologist Association. Chinese expert consensus on dry eye:lifestyle-related dry eye (2022). Zhonghua Yan Ke Za Zhi 2022; 58: 573- 83.

[10]	Huang B, Fei F, Wen H, et al. Impacts of gender and age on meibomian gland in aged people using artificial intelligence. Front Cell Dev Biol 2023; 11: 1199440.

[11]	Mimura T, Yamagami S, Usui T, et al. Changes of conjunctivochalasis with age in a hospital-based study. Am J Ophthalmol 2009; 147: 171- 7.e1.

[12]	Zhang X, Li Q, Zou H, et al. Assessing the severity of conjunctivochalasis in a senile population:a community-based epidemiology study in Shanghai, China. BMC Public Health 2011; 11: 198.

[13]	Gumus K, Pflugfelder SC. Increasing prevalence and severity of conjunctivochalasis with aging detected by anterior segment optical coherence tomography. Am J Ophthalmol 2013; 155: 238- 42.e2.

[14]	Hoh H, Schirra F, Kienecker C, et al. Lid-parallel conjunctival folds are a sure diagnostic sign of dry eye. Ophthalmologe 1995; 92: 802- 8.

[15]	Kang JS, Yi J, Ko MK, et al. Prevalence and risk factors of carbapenem-resistant enterobacteriaceae acquisition in an emergency intensive care unit in a tertiary hospital in Korea:a case-control study. J Korean Med Sci 2019; 34: e140.

[16]	Fricke TR, Tahhan N, Resnikoff S, et al. Global prevalence of presbyopia and vision impairment from uncorrected presbyopia:systematic review, meta-analysis, and modelling. Ophthalmology 2018; 125: 1492- 9.

[17]	Pathai S, Shiels PG, Lawn SD, et al. The eye as a model of ageing in translational research-molecular, epigenetic and clinical aspects. Ageing Res Rev 2013; 12: 490- 508.

[18]	Sinha T, Makia M, Du J, et al. Flavin homeostasis in the mouse retina during aging and degeneration. J Nutr Biochem 2018; 62: 123- 33.

[19]	Dimopoulos IS, Freund PR, Redel T, et al. Changes in rod and cone-driven oscillatory potentials in the aging human retina. Invest Ophthalmol Vis Sci 2014; 55: 5058- 73.

[20]	De Silva MEH, Hill LJ, Downie LE, et al. The effects of aging on corneal and ocular surface homeostasis in mice. Invest Ophthalmol Vis Sci 2019; 60: 2705- 15.

[21]	Galgauskas S, Norvydaitė D, Krasauskaitė D, et al. Age-related changes in corneal thickness and endothelial characteristics. Clin Interv Aging 2013; 8: 1445- 50.

[22]	Chylack LT Jr, Leske MC, McCarthy D, et al. Lens opacities classification system II (LOCS II). Arch Ophthalmol 1989; 107: 991- 7.

[23]	Emery JM, Little JH. Phacoemulsification and Aspiration of Cataracts:Surgical Techniques, Complications, and Results. St. Louis:Mosby, 1979, xv, 325 p.

[24]	Ivanova T, Jalil A, Antoniou Y, et al. Vitrectomy for primary symptomatic vitreous opacities:an evidence-based review. Eye (Lond) 2016; 30: 645- 55.

[25]	Tsukahara M, Mori K, Gehlbach PL, et al. Posterior vitreous detachment as observed by wide-angle OCT imaging. Ophthalmology 2018; 125: 1372- 83.

[26]	Cui X, Buonfiglio F, Pfeiffer N, et al. Aging in ocular blood vessels:molecular insights and the role of oxidative stress. Biomedicines 2024; 12: 817.

[27]	Dias SB, de Lemos L, Sousa L, et al. Age-related changes of the synucleins profile in the mouse retina. Biomolecules 2023; 13: 180.

[28]	Kovacs-Valasek A, Pöstyéni E, Dénes V, et al. Age-related alterations of proteins in albino wistar rat retina. Cells Tissues Organs 2021; 210: 135- 50.

[29]	Zhu Z, Shi D, Guankai P, et al. Retinal age gap as a predictive biomarker for mortality risk. Br J Ophthalmol 2023; 107: 547- 54.

[30]	Hu W, Wang W, Wang Y, et al. Retinal age gap as a predictive biomarker of future risk of Parkinson's disease. Age Ageing 2022; 51: 1- 9.

[31]	Popovic N, Ždralević M, Vujosevic S, et al. Retinal microvascular complexity as a putative biomarker of biological age:a pilot study. Biogerontology 2023; 24: 971- 85.

[32]	Sandell JH, Peters A. Effects of age on nerve fibers in the rhesus monkey optic nerve. J Comp Neurol 2001; 429: 541- 53.

[33]	White KE, Davies VJ, Hogan VE, et al. OPA1 deficiency associated with increased autophagy in retinal ganglion cells in a murine model of dominant optic atrophy. Invest Ophthalmol Vis Sci 2009; 50: 2567- 71.

[34]	Lisak RP, Bealmear B, Nedelkoska L, et al. Secretory products of central nervous system glial cells induce Schwann cell proliferation and protect from cytokine-mediated death. J Neurosci Res 2006; 83: 1425- 31.

[35]	Zawadzka M, Franklin RJ. Myelin regeneration in demyelinating disorders:new developments in biology and clinical pathology. Curr Opin Neurol 2007; 20: 294- 8.

[36]	Nadal-Nicolas FM, Vidal-Sanz M, Agudo-Barriuso M. The aging rat retina:from function to anatomy. Neurobiol Aging 2018; 61: 146- 68.

[37]	Tarau IS, Berlin A, Curcio CA, et al. The cytoskeleton of the retinal pigment epithelium:from normal aging to age-related macular degeneration. Int J Mol Sci 2019; 20: 3578.

[38]	Shamsi FA, Partal A, Sady C, et al. Immunological evidence for methylglyoxal-derived modifications in vivo. Determination of antigenic epitopes. J Biol Chem 1998; 273: 6928- 36.

[39]	Beattie JR, Pawlak AM, McGarvey JJ, et al. Sclera as a surrogate marker for determining AGE-modifications in Bruch's membrane using a Raman spectroscopybased index of aging. Invest Ophthalmol Vis Sci 2011; 52: 1593- 8.

[40]	Trinkaus-Randall V, Tong M, Thomas P, et al. Confocal imaging of the alpha 6 and beta 4 integrin subunits in the human cornea with aging. Invest Ophthalmol Vis Sci 1993; 34: 3103- 9.

[41]	Onouchi H, Ishii T, Miyazawa M, et al. Mitochondrial superoxide anion overproduction in Tet-mev-1 transgenic mice accelerates age-dependent corneal cell dysfunctions. Invest Ophthalmol Vis Sci 2012; 53: 5780- 7.

[42]	Roh DS, Du Y, Gabriele ML, et al. Age-related dystrophic changes in corneal endothelium from DNA repair-deficient mice. Aging Cell 2013; 12: 1122- 31.

[43]	Gary AS, Dorr MM, Rochette PJ. The T414G mitochondrial DNA mutation:a biomarker of ageing in human eye. Mutagenesis 2021; 36: 187- 92.

[44]	Hsueh YJ, Wang D-Y, Cheng C-C, et al. Age-related expressions of p63 and other keratinocyte stem cell markers in rat cornea. J Biomed Sci 2004; 11: 641- 51.

[45]	McFall-Ngai M, Horwitz J, Ding LL, et al. Age-dependent changes in the heat-stable crystallin, beta Bp, of the human lens. Curr Eye Res 1986; 5: 387- 94.

[46]	Garner B, Vazquez S, Griffith R, et al. Identification of glutathionyl-3-hydroxykynurenine glucoside as a novel fluorophore associated with aging of the human lens. J Biol Chem 1999; 274: 20847- 54.

[47]	Itakura H, Kishi S. Aging changes of vitreomacular interface. Retina 2011; 31: 1400- 4.

[48]	van Deemter M, Pas HH, Kuijer R, et al. Enzymatic breakdown of type II collagen in the human vitreous. Invest Ophthalmol Vis Sci 2009; 50: 4552- 60.

[49]	Vaughan-Thomas A, Gilbert SJ, Duance VC. Elevated levels of proteolytic enzymes in the aging human vitreous. Invest Ophthalmol Vis Sci 2000; 41: 3299- 304.

[50]	Ohno-Matsui K. Parallel findings in age-related macular degeneration and Alzheimer's disease. Prog Retin Eye Res 2011; 30: 217- 38.

[51]	Hoh Kam J, Lenassi E, Jeffery G. Viewing ageing eyes:diverse sites of amyloid beta accumulation in the ageing mouse retina and the up-regulation of macrophages. PLoS One 2010; 5: e13127.

[52]	Liu C, Cao L, Yang S, et al. Subretinal injection of amyloid-beta peptide accelerates RPE cell senescence and retinal degeneration. Int J Mol Med 2015; 35: 169- 76.

[53]	Ravichandran S, Snyder PJ, Alber J, et al. Association and multimodal model of retinal and blood-based biomarkers for detection of preclinical Alzheimer's disease. Alzheimers Res Ther 2025; 17: 19.

[54]	Augustin S, Lam M, Lavalette S, et al. Melanophages give rise to hyperreflective foci in AMD, a disease-progression marker. J Neuroinflammation 2023; 20: 28.

[55]	Zhu D, Wu J, Spee C, et al. BMP4 mediates oxidative stressinduced retinal pigment epithelial cell senescence and is overexpressed in age-related macular degeneration. J Biol Chem 2009; 284: 9529- 39.

[56]	Han S, Lu Q, Wang N. Apr3 accelerates the senescence of human retinal pigment epithelial cells. Mol Med Rep 2016; 13: 3121- 6.

[57]	Huang Y, Syed MG, Chen R, et al. Genomic determinants of biological age estimated by deep learning applied to retinal images. Geroscience 2025; 47: 2613- 29.

[58]	Yi W, Lu Y, Zhong S, et al. A single-cell transcriptome atlas of the aging human and macaque retina.Natl Sci Rev 2021; 8: nwaa179.

[59]	Hannum G, Guinney J, Zhao L, et al. Genome-wide methylation profiles reveal quantitative views of human aging rates. Mol Cell 2013; 49: 359- 67.

[60]	Chen D, Chao DL, Rocha L, et al. The lipid elongation enzyme ELOVL2 is a molecular regulator of aging in the retina. Aging Cell 2020; 19: e13100.

[61]	Dubey SK, Dubey R, Prajapati SC, et al. Histone deficiency and hypoacetylation in the aging retinal pigment epithelium. Aging Cell 2024; 23: e14108.

[62]	Kinser HE, Pincus Z. MicroRNAs as modulators of longevity and the aging process. Hum Genet 2020; 139: 291- 308.

[63]	Akamine PS, Lima CR, Lustoza-Costa GJ, et al. Age-related increase of let-7 family microRNA in rat retina and vitreous. Exp Eye Res 2021; 204: 108434.

[64]	Smit-McBride Z, Forward KI, Nguyen AT, et al. Age-dependent increase in miRNA-34a expression in the posterior pole of the mouse eye. Mol Vis 2014; 20: 1569- 78.

[65]	Hao Y, Zhou Q. miR-146a is upregulated during retinal pigment epithelium (RPE)/choroid aging in mice and represses IL-6 and VEGF-A expression in RPE cells. J Clin Exp Ophthalmol 2016; 7: 562.

[66]	Hermenean A, Trotta MC, Gharbia S, et al. Changes in retinal structure and ultrastructure in the aged mice correlate with differences in the expression of selected retinal miRNAs. Front Pharmacol 2020; 11: 593514.

[67]	Qu J, Kaufman Y, Washington I. Coenzyme Q10 in the human retina. Invest Ophthalmol Vis Sci 2009; 50: 1814- 8.

[68]	Jadeja RN, Powell FL, Jones MA, et al. Loss of NAMPT in aging retinal pigment epithelium reduces NAD(+) availability and promotes cellular senescence.Aging (Albany NY) 2018; 10: 1306- 23.

[69]	Mu W, Han X, Tong M, et al. Identification of the metabolic signature of aging retina. Transl Vis Sci Technol 2024; 13: 8.

[70]	Kawai M, Ogawa Y, Shimmura S, et al. Expression and localization of aging markers in lacrimal gland of chronic graft-versushost disease. Sci Rep 2013; 3: 2455.

[71]	Jung YH, Ryu J-S, Yoon C-H, et al. Age-dependent distinct distributions of dendritic cells in autoimmune dry eye murine model.Cells 2021; 10: 1857.

[72]	Rocha EM, Alves M, Rios JD, et al. The aging lacrimal gland:changes in structure and function. Ocul Surf 2008; 6: 162- 74.

[73]	Micera A, Di Zazzo A, Esposito G, et al. Age-related changes to human tear composition. Invest Ophthalmol Vis Sci 2018; 59: 2024- 31.

[74]	Wolf J, Rasmussen DK, Sun YJ, et al. Liquid-biopsy proteomics combined with AI identifies cellular drivers of eye aging and disease in vivo. Cell 2023; 186: 4868- 84.e12.