Evidence for reduction of pro-atherosclerotic properties in platelets from healthy centenarians

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Abstract

The aim of the present study was to investigate if aging is associated with platelet membrane modifications possibly related with cellular activation and hyperaggregability and if platelets from centenarians show different properties which might play a role in successful aging and longevity.

Platelet plasma membranes were obtained from 60 healthy subjects, divided into four groups according to the age range: (1) 21–39 years; (2) 40–59 years; (3) 60–79 years; (4) centenarians (≥100 years). Both centenarians and control subjects were submitted to the following inclusion criteria: liver, kidney, and thyroid function tests within the normal range; absence of history of diabetes, hypertension or coronary heart disease; no signs of edema or dehydration; no drug or vitamin supplement in the 4 weeks before the study; absence of Alzheimer's disease or secondary dementia. The following determinations were performed: lipid peroxide levels (Lp) evaluated by the measurement of thiobarbituric acid (TBA) reactivity, fluidity studied by the fluorescence anisotropy of the probe 1-(4-trimethylaminophenyl)-6-phenyl-1,3,5-hexatriene (TMA-DPH), Na+/K+-ATPase activity measured by the method of Kitao and Hattori, and sialic acid (SA) content evaluated by the periodate–thiobarbituric acid method. Centenarians showed: (i) Lp concentrations lower than elderly subjects; (ii) increased Na+/K+-ATPase activity compared with adult and elderly subjects; (iii) higher TMA-DPH anisotropy than elderly subjects; (iv) SA content similar to the young and adult groups.

The present work found deep platelet membrane modifications in centenarians compared with elderly subjects. These changes are likely associated with a decreased platelet activation and therefore might exert a protective role against cardiovascular accidents, as platelet activation is a key event in the initiation and progression of arteriosclerosis.

Introduction

Cardiovascular diseases are the major cause of morbidity and mortality in the elderly (Massarelli et al., 2000, Walsh, 1987). Multiple factors might be responsible for the increased incidence of arterial thromboembolism during aging. In particular, a central role might be played by platelet activation with enhanced cellular responsiveness to aggregating stimuli, high levels of beta-thromboglobulin and increased production of thromboxane A2 (Abbate et al., 1993).

Studies performed on experimental animals demonstrated an association between the enhancement of platelet aggregation during aging and changes in membrane microviscosity and lipid composition (Hossain et al., 1999). The age-related deterioration of platelet membrane fluidity in rats has been ascribed not only to a higher membrane cholesterol/phospholipid molar ratio (Hossain et al., 1999) but also to increased basal levels of lipid peroxides in old animals (Hossain et al., 1999).

The data reporting age-related alterations in platelet membrane fluidity in experimental animals are not fully confirmed by data obtained in elderly humans, in which either no change (Noble et al., 1999) or an increase in the membrane structural order (Marinho et al., 1997) were described. Moreover, it is not currently available in the literature a study investigating in human aging the relations among the platelet membrane physicochemical properties (fluidity), lipid peroxidation, sialic acid content—which has been involved in the process of platelet senescence in animals (Kotze et al., 1993)—and activities of membrane-bound enzymes.

It can be supposed that centenarians have both a genetic and a phenotipic profile that have protected them from cardiovascular death. A previous work by our group has recently found that platelets from centenarians are resistant to the homocysteine-induced inhibition of nitric oxide production and has suggested that this feature observed in platelets might be one of the mechanisms at the basis of successful aging (Mutus et al., 2000).

The aim of the present study was to investigate if aging is associated with platelet membrane modifications possibly related with cellular activation and hyperaggregability and if platelets from centenarians show different properties which might play a role in successful aging and longevity.

Correlation studies were performed among the parameters studied, as it has long been known that the platelet membrane physicochemical properties evaluated as fluidity might be related with membrane lipid peroxidation, sialic acid content and activities of membrane-bound enzymes (Lenaz, G., 1987).

Section snippets

Subjects

The study was performed in 60 subjects, divided into four groups according to the age range: (1) 21–39 years (n=15); (2) 40–59 years (n=15); (3) 60–79 years (n=15); (4) centenarians (≥100 years) (n=15). Both centenarians and control subjects were recruited from central Italy and submitted to the following inclusion criteria: liver, kidney, and thyroid function tests within the normal range; absence of history of diabetes, hypertension or coronary heart disease; no signs of edema or dehydration;

Lipid peroxide levels

Table 2 shows the basal lipid peroxide levels, evaluated as MDA content, in the platelet membranes obtained from the four age groups. The Lp content progressively increased from 21 to 39 years until 60–79 years, being significantly higher in elderly subjects (60–79 years) than in young (21–39 years) and adult subjects (40–59 years). On the contrary, in centenarians the MDA concentrations were significantly reduced in comparison with elderly subjects (p<0.01 vs. 60–79 years), being still higher

Discussion

The present study indicated an age-associated trend in the platelet membrane concentrations of a biomarker of oxidative stress (MDA), which showed a progressive increase from the subjects aged 21–39 years to 60–79 years. These results are consistent with the hypothesis suggesting that the oxidative damage plays a central role in senescence. A large and rapidly growing body of evidences supports this hypothesis (Beckman and Ames, 1998), but at present only a few specific cellular targets have

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