Instability of the cellular lipidome with age

Abstract

The human lens nucleus is formed in utero, and from birth onwards, there appears to be no significant turnover of intracellular proteins or membrane components. Since, in adults, this region also lacks active enzymes, it offers the opportunity to examine the intrinsic stability of macromolecules under physiological conditions. Fifty seven human lenses, ranging in age from 12 to 82 years, were dissected into nucleus and cortex, and the nuclear lipids analyzed by electrospray ionization tandem mass spectrometry. In the first four decades of life, glycerophospholipids (with the exception of lysophosphatidylethanolamines) declined rapidly, such that by age 40, their content became negligible. In contrast the level of ceramides and dihydroceramides, which were undetectable prior to age 30, increased approximately 100-fold. The concentration of sphingomyelins and dihydrosphingomyelins remained unchanged over the whole life span. As a consequence of this marked alteration in composition, the properties of fiber cell membranes in the centre of young lenses are likely to be very different from those in older lenses. Interestingly, the identification of age 40 years as a time of transition in the lipid composition of the nucleus coincides with previously reported macroscopic changes in lens properties (e.g., a massive age-related increase in lens stiffness) and related pathologies such as presbyopia. The underlying reasons for the dramatic change in the lipid profile of the human lens with age are not known, but are most likely linked to the stability of some membrane lipids in a physiological environment.

Proteomic Analysis of Lipid Raft-Like Detergent-Resistant Membranes of Lens Fiber Cells

“…Considering the important functions of lipid raft domains in other cell types, including roles in trafficking, signal transduction, apoptosis, and cytoskeletal organization, it will be interesting to study the role of lens fiber cell lipid rafts in differentiation as well as in cell migration and elongation. Considering different lipid composition between human and bovine lens, 66 as well as lipid changes with aging, 67 further characterization of the lipid raft proteome in the human lens is warranted. It also will be interesting to study whether lipid rafts play a role in lens protein aggregation during lens aging, given their increased affinity for oligomeric proteins, particularly in neurodegenerative diseases.…”

Role of sphingolipids in senescence: implication in aging and age-related diseases

“…A flurry of recent studies have addressed the potential roles of blood sphingolipids as possible biomarkers for aging and agingrelated diseases. Clinical studies have made significant correlations between the levels of sphingolipids, specifically Cer, and sphingolipid enzymes and different pathologies such as atherosclerosis, cataract, AD, and type 2 diabetes (96,(122)(123)(124).…”

Potential therapeutic target for aging and age-related neurodegenerative diseases: the role of acid sphingomyelinase

“…Thus, sphingolipid abnormalities are increasingly becoming recognized as potential causes of several aging-related neurodegenerative diseases [8][9][10][11][12][13][14][15][16] . Recently, blood sphingolipids have been considered to be possible biomarkers for these diseases [17][18][19] .…”