Age-related impairment of HDL-mediated cholesterol efflux

Berrougui, Hicham; Isabelle, Maxim; Cloutier, Martin; Grenier, Guillaume; Khalil, Abdelouahed

doi:10.1194/jlr.m600167-jlr200

Cited by 73 publications

(59 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…While T cells from young subjects recovered membrane fluidity after 24h, T cells from elderly subjects exhibited fluctuations in membrane fluidity over the time course tested here. These data confirmed that HDL from elderly subjects are unable to support efficient cholesterol efflux (Berrougui et al 2007) and may contribute to functional alterations in the T cell membrane.…”

Section: High Membrane Cholesterol Content Is Associated With Alteredsupporting

confidence: 74%

Immunomodulatory role of high-density lipoproteins: impact on immunosenescence

Larbi

Fortin

Dupuis

et al. 2014

AGE

Self Cite

View full text Add to dashboard Cite

Natural aging is accompanied by a dysregulation of the host immune response that has well-known clinical consequences but poorly defined underlying causes. It has previously been reported that advancing age is associated with an increase in membrane cholesterol level in T cells. The aim of this study was to investigate whether high-density lipoprotein (HDL) can modulate the age-related accumulation of membrane cholesterol in T cells and impact on their subsequent responsiveness. Our data reveal that cholesterol metabolism, influx, and efflux are altered in T cells with aging, which may in part explain the increase in membrane cholesterol level observed in T cells in elderly individuals. HDL was unable to promote reverse cholesterol transport in T cells from elderly subjects with the same efficiency as was observed in T cells from young subjects besides unchanged ABCA-1 and SR-BI expressions. HDL exhibited a short-acting co-stimulatory effect by enhancing T cell production of interleukin-2 (IL-2). Moreover, HDL from healthy normolipemic individuals exerted differential effects on T cell proliferation that depended on the age of the HDL donor. Finally, HDL modulated TCR/CD28 activation by inducing sustained signaling through pLck, pERK, and pAkt. These data suggest that HDL has immunomodulatory effects on T cells that are influenced by age.

show abstract

Section: High Membrane Cholesterol Content Is Associated With Alteredsupporting

confidence: 74%

Immunomodulatory role of high-density lipoproteins: impact on immunosenescence

Larbi

Fortin

Dupuis

et al. 2014

AGE

Self Cite

View full text Add to dashboard Cite

show abstract

“…27 Age-dependent reductions in LPL or LCAT activity and HDL particle size are possible reasons. These alterations, however, greatly vary and seem to have a strong genetic background.…”

Section: Influence Of Age On Hdl Particlementioning

confidence: 99%

“…26 The activity of enzymes involved in HDL formation and conversion of HDL subclasses may change as persons age. 27,30 Moreover, most of the HDL signaling pathways 40 -50 are potentially compromised in aged cells. 24 -26 For example, cdc42 activity is reduced in senescent cells and may contribute to impairement of lipid transport in Werner syndrome.…”

Section: Other Cell and Plasma Proteins Involved In Cholesterol Homeomentioning

confidence: 99%

Interrelationships Among HDL Metabolism, Aging, and Atherosclerosis

Walter

2009

ATVB

105

View full text Add to dashboard Cite

Abstract-HDL plasma concentrations decline with age in prospective studies. Decline in HDL concentration and function may occur secondary because of hormonal changes, inflammatory processes, and diabetes mellitus. Beyond these effects specific aging processes may be involved. Replicative aging, the telomere-driven loss of divisional capacity, is a species-specific aging mechanism that may decrease HDL concentration and function. Cross-sectionally, by contrast, HDL levels do not change much or even slightly increase with age, suggesting that only people with still high HDL concentrations survive. A selection bias by HDL lowering genetic variation may explain why HDL deficiency is extremely rare among centenarians. Vice versa, HDL may modulate the aging process, not only by its well-known antiatherogenic effects, eg, its ability to remove cellular lipids and by antiatherogenic pleiotropic effects on cell survival, but possibly also by direct interfering with aging signaling or survival factor KLOTHO. Most of the current findings, however, are based on cell culture and selected animal experiments and await further confirmation by appropriate in vivo models. T he influence of age on atherosclerosis is generally explained by the simple passage of time and a higher number and severity of risk factors with increasing age. However, the observation of senescence-like changes in atherosclerotic lesions, 1 the severe atherosclerosis in premature aging syndromes, 2 and the identification of age as by far the most predictive independent risk factor for atherosclerosis effective even in absence of other risk factors 3 suggests that atherogenesis is more directly related to the aging process than previously presumed.Aging is a complex process that (on the cellular level) includes cell cycle arrest, morphology remodeling with functional decline, chromatin silencing with profound gene expression changes, and changes in metabolism. As summarized in Figure 1, different triggers may act together in a cooperative fashion and use overlapping signaling pathways to induce and propagate the aging process. 4 Replicative aging results from the progressive shortening of telomeres (composed of conserved nucleotide sequences, TTAGGG in vertebrates) attributable to incomplete end replication during cell divisions. It may protect against increased cancer risk but may also contribute to atherosclerosis in later life, particularly at "atherosclerosis-prone areas" with high replication rates. 5 Next to age, a low high-density lipoprotein (HDL) cholesterol level is one of the strongest predictors of premature coronary heart disease and stroke. 6 In contrast to high low-density lipoprotein (LDL) cholesterol, low HDL cholesterol remains a powerful risk predictor into old age. HDL may directly influence specific aging processes and, vice versa, aging may influence HDL concentration and function. However, it is important to bear in mind the caveats of the current studies. First, most findings are based on cell culture and animal models and have not be...

show abstract

“…The properties of HDL particles, the levels of HDL-C and the genetic contribution to HDL-C change with age [89,90 ]. For example, in a longitudinal study [89], the APOE isoform polymorphism influenced HDL-C in an age-dependent manner.…”

Section: Hdl-c Level Is An Emergent Property Of a Dynamic Systemmentioning

confidence: 98%