Limits...
No turnover in lens lipids for the entire human lifespan.

Hughes JR, Levchenko VA, Blanksby SJ, Mitchell TW, Williams A, Truscott RJ - Elife (2015)

Bottom Line: In this study, we present an intriguing counter-example by demonstrating that in the center of the human ocular lens, there is no lipid turnover in fiber cells during the entire human lifespan.This discovery, combined with prior demonstration of pronounced changes in the lens lipid composition over a lifetime (Hughes et al., 2012), suggests that some lipid classes break down in the body over several decades, whereas others are stable.Whether long-lived lipids are present in other tissues is not yet known, but this may prove to be important in understanding the development of age-related diseases.

View Article: PubMed Central - PubMed

Affiliation: School of Medicine, University of Wollongong, Wollongong, Australia.

ABSTRACT
Lipids are critical to cellular function and it is generally accepted that lipid turnover is rapid and dysregulation in turnover results in disease (Dawidowicz 1987; Phillips et al., 2009; Liu et al., 2013). In this study, we present an intriguing counter-example by demonstrating that in the center of the human ocular lens, there is no lipid turnover in fiber cells during the entire human lifespan. This discovery, combined with prior demonstration of pronounced changes in the lens lipid composition over a lifetime (Hughes et al., 2012), suggests that some lipid classes break down in the body over several decades, whereas others are stable. Such substantial changes in lens cell membranes may play a role in the genesis of age-related eye disorders. Whether long-lived lipids are present in other tissues is not yet known, but this may prove to be important in understanding the development of age-related diseases.

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Analysis of lens membrane lipid 14C content demonstrates a lack of molecular turnover.(A) The fraction of modern 14C present in the membrane lipids of human lens nuclear regions. The lipid samples (•) are superimposed over the levels of artificial 14CO2 present in the atmosphere in the northern hemisphere (light gray) and the southern hemisphere (dark gray) from 1950 until 1990 (Hua et al., 2013). (B) The correlation between the predicted year of birth as calculated from the measured fraction of modern 14C present in lens membrane lipids and the actual year of birth of each individual. The slope was approximately one (0.98 ± 0.04) and the y-intercept was indistinguishable from zero within the measured error (39 ± 75). Vertical error bars: ± sigma. Horizontal error bars: year of birth ± six months.DOI:http://dx.doi.org/10.7554/eLife.06003.003
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fig1: Analysis of lens membrane lipid 14C content demonstrates a lack of molecular turnover.(A) The fraction of modern 14C present in the membrane lipids of human lens nuclear regions. The lipid samples (•) are superimposed over the levels of artificial 14CO2 present in the atmosphere in the northern hemisphere (light gray) and the southern hemisphere (dark gray) from 1950 until 1990 (Hua et al., 2013). (B) The correlation between the predicted year of birth as calculated from the measured fraction of modern 14C present in lens membrane lipids and the actual year of birth of each individual. The slope was approximately one (0.98 ± 0.04) and the y-intercept was indistinguishable from zero within the measured error (39 ± 75). Vertical error bars: ± sigma. Horizontal error bars: year of birth ± six months.DOI:http://dx.doi.org/10.7554/eLife.06003.003

Mentions: We carefully dissected nuclei from individual human lenses of 23 donors of known birth dates. The average human lens nucleus is approximately 6–7 mm in diameter (Hermans et al., 2007). Therefore, to avoid contamination of fiber cells laid down postnatally, we cut a cylinder of 4.5 mm in diameter in the axial plane using a trephine, then removed 1 mm from either end as previously described (Friedrich and Truscott, 2009). Total lipids present in each lens nucleus were obtained using a well-established method that reports high yield of lipids and minimal protein contamination (Folch et al., 1957). Since protein is the major component of lenses by mass and lens proteins are known to be present since birth (Stewart et al., 2013), the residual protein content of lipid extracts was determined using a standard BCA assay (Smith et al., 1985). Residual protein was found to represent less than 0.5% of the total weight of carbon in the extract, and therefore a negligible contribution to the 14C measurement. Radiocarbon content in lens lipids was determined by AMS and was found to closely match the atmospheric levels of the date of birth (Figure 1A).10.7554/eLife.06003.003Figure 1.Analysis of lens membrane lipid 14C content demonstrates a lack of molecular turnover.


No turnover in lens lipids for the entire human lifespan.

Hughes JR, Levchenko VA, Blanksby SJ, Mitchell TW, Williams A, Truscott RJ - Elife (2015)

Analysis of lens membrane lipid 14C content demonstrates a lack of molecular turnover.(A) The fraction of modern 14C present in the membrane lipids of human lens nuclear regions. The lipid samples (•) are superimposed over the levels of artificial 14CO2 present in the atmosphere in the northern hemisphere (light gray) and the southern hemisphere (dark gray) from 1950 until 1990 (Hua et al., 2013). (B) The correlation between the predicted year of birth as calculated from the measured fraction of modern 14C present in lens membrane lipids and the actual year of birth of each individual. The slope was approximately one (0.98 ± 0.04) and the y-intercept was indistinguishable from zero within the measured error (39 ± 75). Vertical error bars: ± sigma. Horizontal error bars: year of birth ± six months.DOI:http://dx.doi.org/10.7554/eLife.06003.003
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4384533&req=5

fig1: Analysis of lens membrane lipid 14C content demonstrates a lack of molecular turnover.(A) The fraction of modern 14C present in the membrane lipids of human lens nuclear regions. The lipid samples (•) are superimposed over the levels of artificial 14CO2 present in the atmosphere in the northern hemisphere (light gray) and the southern hemisphere (dark gray) from 1950 until 1990 (Hua et al., 2013). (B) The correlation between the predicted year of birth as calculated from the measured fraction of modern 14C present in lens membrane lipids and the actual year of birth of each individual. The slope was approximately one (0.98 ± 0.04) and the y-intercept was indistinguishable from zero within the measured error (39 ± 75). Vertical error bars: ± sigma. Horizontal error bars: year of birth ± six months.DOI:http://dx.doi.org/10.7554/eLife.06003.003
Mentions: We carefully dissected nuclei from individual human lenses of 23 donors of known birth dates. The average human lens nucleus is approximately 6–7 mm in diameter (Hermans et al., 2007). Therefore, to avoid contamination of fiber cells laid down postnatally, we cut a cylinder of 4.5 mm in diameter in the axial plane using a trephine, then removed 1 mm from either end as previously described (Friedrich and Truscott, 2009). Total lipids present in each lens nucleus were obtained using a well-established method that reports high yield of lipids and minimal protein contamination (Folch et al., 1957). Since protein is the major component of lenses by mass and lens proteins are known to be present since birth (Stewart et al., 2013), the residual protein content of lipid extracts was determined using a standard BCA assay (Smith et al., 1985). Residual protein was found to represent less than 0.5% of the total weight of carbon in the extract, and therefore a negligible contribution to the 14C measurement. Radiocarbon content in lens lipids was determined by AMS and was found to closely match the atmospheric levels of the date of birth (Figure 1A).10.7554/eLife.06003.003Figure 1.Analysis of lens membrane lipid 14C content demonstrates a lack of molecular turnover.

Bottom Line: In this study, we present an intriguing counter-example by demonstrating that in the center of the human ocular lens, there is no lipid turnover in fiber cells during the entire human lifespan.This discovery, combined with prior demonstration of pronounced changes in the lens lipid composition over a lifetime (Hughes et al., 2012), suggests that some lipid classes break down in the body over several decades, whereas others are stable.Whether long-lived lipids are present in other tissues is not yet known, but this may prove to be important in understanding the development of age-related diseases.

View Article: PubMed Central - PubMed

Affiliation: School of Medicine, University of Wollongong, Wollongong, Australia.

ABSTRACT
Lipids are critical to cellular function and it is generally accepted that lipid turnover is rapid and dysregulation in turnover results in disease (Dawidowicz 1987; Phillips et al., 2009; Liu et al., 2013). In this study, we present an intriguing counter-example by demonstrating that in the center of the human ocular lens, there is no lipid turnover in fiber cells during the entire human lifespan. This discovery, combined with prior demonstration of pronounced changes in the lens lipid composition over a lifetime (Hughes et al., 2012), suggests that some lipid classes break down in the body over several decades, whereas others are stable. Such substantial changes in lens cell membranes may play a role in the genesis of age-related eye disorders. Whether long-lived lipids are present in other tissues is not yet known, but this may prove to be important in understanding the development of age-related diseases.

Show MeSH
Related in: MedlinePlus