In vivo quasi-elastic light scattering eye scanner detects molecular aging in humans and mice

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 measure age-dependent signals in vivo in lenses of both healthy human subjects and wild-type C57BL/6 mice. We hypothesize that cumulative alterations in the lens may constitute an in vivo biomarker of molecular aging.

Methods : Quasi-elastic light scattering (QLS) was used to measure age-dependent changes in vivo in lenses of 34 healthy human subjects without history of eye disease (18 males, 16 females; ages 5–61), and in unanesthetized wild-type C57BL/6 mice aged 3–22 months-old. 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 related QLS metrics can be acquired noninvasively in human subjects and in unanesthetized mice. Age-dependent QLS signal changes detected in vivo in humans and 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 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.