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      Assessment of candidate ocular biomarkers of ageing in a South African adult population: Relationship with chronological age and systemic biomarkers

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          Highlights

          • Structural parameters of the eye change with increasing chronological age.

          • Ocular age-related parameters may serve as biomarkers of aging.

          • Relevant ocular parameters include retinal vessel calibre and lens density.

          Abstract

          Certain anatomic and functional parameters of the eye change with increasing chronological age. They may, therefore, serve as potential biomarkers of ageing. We investigated associations between four such ocular parameters (lens density, retinal vessel calibre, corneal endothelial cells and retinal nerve fibre layer thickness) and two ‘cellular’ biomarkers of ageing (leukocyte telomere length and CDKN2A expression), with frailty (a clinical correlate of biological ageing) in a population of South African adults. All ocular parameters revealed an association with either telomere length or CDKN2A expression. However, lens density was most strongly correlated with age, increased CDKN2A expression, and with frailty ( p = 0.05 and 0.03, respectively). Narrow retinal arteriolar diameter, associated with increased chronological age, was also associated with increased CDK2NA expression (0.42 vs. 0.31, p = 0.02) but not with frailty. Ocular parameters may aid in determining biological age, warranting investigation in longitudinal studies.

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          Most cited references48

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          Oxidative stress shortens telomeres.

          Telomeres in most human cells shorten with each round of DNA replication, because they lack the enzyme telomerase. This is not, however, the only determinant of the rate of loss of telomeric DNA. Oxidative damage is repaired less well in telomeric DNA than elsewhere in the chromosome, and oxidative stress accelerates telomere loss, whereas antioxidants decelerate it. I suggest here that oxidative stress is an important modulator of telomere loss and that telomere-driven replicative senescence is primarily a stress response. This might have evolved to block the growth of cells that have been exposed to a high risk of mutation.
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            Healthy life expectancy for 187 countries, 1990–2010: a systematic analysis for the Global Burden Disease Study 2010

            The Lancet, 380(9859), 2144-2162
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              Expression of p16(INK4a) in peripheral blood T-cells is a biomarker of human aging.

              Expression of the p16(INK4a) tumor suppressor sharply increases with age in most mammalian tissues, and contributes to an age-induced functional decline of certain self-renewing compartments. These observations have suggested that p16(INK4a) expression could be a biomarker of mammalian aging. To translate this notion to human use, we determined p16(INK4a) expression in cellular fractions of human whole blood, and found highest expression in peripheral blood T-lymphocytes (PBTL). We then measured INK4/ARF transcript expression in PBTL from two independent cohorts of healthy humans (170 donors total), and analyzed their relationship with donor characteristics. Expression of p16(INK4a), but not other INK4/ARF transcripts, appeared to exponentially increase with donor chronologic age. Importantly, p16(INK4a) expression did not independently correlate with gender or body-mass index, but was significantly associated with tobacco use and physical inactivity. In addition, p16(INK4a) expression was associated with plasma interleukin-6 concentration, a marker of human frailty. These data suggest that p16(INK4a) expression in PBTL is an easily measured, peripheral blood biomarker of molecular age.
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                Author and article information

                Contributors
                Journal
                Mech Ageing Dev
                Mech. Ageing Dev
                Mechanisms of Ageing and Development
                Elsevier Science Ireland
                0047-6374
                1872-6216
                1 July 2013
                July 2013
                : 134
                : 7-8
                : 338-345
                Affiliations
                [a ]International Centre for Eye Health, Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine (LSHTM), Keppel Street, London WC1E 7HT, UK
                [b ]Desmond Tutu HIV Centre, Institute of Infectious Diseases and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Anzio Road, Observatory 7925, Cape Town, South Africa
                [c ]Department of Clinical Research, Faculty of Infectious and Tropical Diseases, LSHTM, Keppel Street, London WC1E 7HT, UK
                [d ]MRC Tropical Epidemiology Group, Faculty of Epidemiology and Population Health, LSHTM, Keppel Street, London WC1E 7HT, UK
                [e ]NIHR Biomedical Research Centre for Ophthalmology, Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, 162 City Road, London EC1V 2PD, UK
                [f ]Department of Ophthalmology, Groote Schuur Hospital, University of Cape Town, Observatory 7925, Cape Town, South Africa
                [g ]Singapore Eye Research Institute, National University of Singapore, 11 Third Hospital Avenue, Singapore 168751, Singapore
                [h ]Institute of Cancer Sciences, College of Medical, Veterinary & Life Sciences, University of Glasgow, Glasgow, UK
                Author notes
                [* ]Corresponding author at: International Centre for Eye Health, Department of Clinical Research, LSHTM, Keppel Street, WC1E 7HT, UK. Tel.: +44 20 7958 8343; fax: +44 20 7958 8325. Sophia.pathai@ 123456lshtm.ac.uk sophia.pathai@ 123456gmail.com
                Article
                S0047-6374(13)00061-4
                10.1016/j.mad.2013.05.002
                3710972
                23701820
                6e6f3bef-59aa-40d8-b1b3-71f426841835
                © 2013 The Authors

                This document may be redistributed and reused, subject to certain conditions.

                History
                : 17 January 2013
                : 27 April 2013
                : 11 May 2013
                Categories
                Article

                Developmental biology
                telomeres,cdkn2a,lens density,retinal vessel calibre,corneal endothelium,retinal nerve fibre layer,frailty

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