Abstract
Purpose :
The absence of clinical tools to evaluate individual variation in the pace of aging represents a major impediment to understanding aging and maximizing health throughout life. The lens is an ideal tissue for quantitative assessment of molecular aging in vivo. Long-lived proteins in lens fiber cells are expressed during fetal life, do not undergo turnover, accumulate molecular alterations throughout life, and are optically accessible in vivo. The study purpose was to longitudinally measure both age- and glycemia-dependent signals in vivo in lenses of control C57BL/6 mice and mice with diabetes. We hypothesized that cumulative alterations in the lens may constitute an in vivo biomarker of molecular aging, and that the rate of accumulation would increase in mice with chronic hyperglycemia.
Methods :
Quasi-elastic light scattering (QLS) was used to longitudinally measure in vivo (i) age-dependent changes in lenses of unanesthetized wild-type C57BL/6 mice aged 4–18 months-old, and (ii) glycemia-dependent changes in lenses of unanesthetized C57BL/6 mice aged 4–8 months-old treated with streptozotocin to induce chronic hyperglycemia. We also examined time-dependent effects of in situ oxidation on QLS signals obtained from water-soluble human lens protein extract (hLPE) during long-term incubation in vitro.
Results :
Our results indicated that aging and glycemia related QLS metrics can be acquired noninvasively in lenses of unanesthetized mice across a wide age range. QLS scattering intensity and correlation time measured longitudinally increased linearly with age in wild-type mice. The age-dependent QLS signal changes detected in vivo in mice recapitulated time-dependent changes in hydrodynamic radius, protein polydispersity, and supramolecular order of human lens proteins during long-term incubation (~1 year) and in response to sustained oxidation (~2.5 months) in vitro.
Conclusions :
Our findings demonstrate that QLS analysis of lens proteins provides a practical technique for noninvasive assessment of molecular aging in vivo.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.