Longevity and the  2 Allele of Apolipoprotein E: The Finnish Centenarians Study

Frisoni, Giovanni B.; Louhija, Jukka; Geroldi, Cristina; Trabucchi, Marco

doi:10.1093/gerona/56.2.m75

Cited by 67 publications

(42 citation statements)

References 31 publications

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“…The prevalence of the ⑀ 4 allele in our sample was low (8.5%), but it was very similar to those previously reported by other Italian authors (34). Recently, an association between the ⑀ 2 allele and extreme longevity has been reported in the Finnish Centenarians Study (35). Our data do not support a role of apo E polymorphism in VaSA; nevertheless, the very low prevalence of both ⑀ 4 and ⑀ 2 alleles might reduce the possibility of detecting significant differences among the groups.…”

Section: Discussionsupporting

confidence: 92%

Genetic Factors Associated With the Absence of Atherosclerosis in Octogenarians

Zuliani¹,

Cherubini²,

Volpato³

et al. 2002

The Journals of Gerontology Series A: Biological Sciences and M

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Background . Atherosclerosis (ATS) is a common age-related disease of large arteries. The prevalence of older subjects with vascular successful aging (VaSA), defined as the absence of clinical symptoms and instrumental signs of ATS, is low in Western countries. The possible contribution of genetics to the VaSA phenomenon is not known. THEROSCLEROSIS (ATS), a progressive age-related disease of the large arteries characterized by the accumulation of lipids and fibrous elements, is the primary cause of coronary heart disease (CHD) and stroke, and represents the underlying cause of about 50% of all deaths in Western countries (1). The prevalence of ATS increases significantly with age, and only a few older individuals have no evidence of ATS when evaluated at one vascular site, for instance the carotid arteries (2). The percentage of older subjects without ATS in several vascular districts is not known, but it is conceivably much smaller. This highly selected group might represent a useful model to investigate the factors that protect against the development of ATS and allow the individual to achieve successful aging at the vascular level (3). In a previous study, we found that very old ATS-free subjects have higher plasma levels of vitamin E and lower levels of low-density lipoprotein (LDL) oxidation compared with age-matched controls with documented ATS (4). However, epidemiological studies have shown that not only environmental but also genetic factors contribute to the development of the atherosclerotic plaques. Indeed, it has been suggested that the fraction of disease explained by genetics within a population is high and often exceeds 50% (1). MethodsATS is considered a polygenic disease, and, in the past few years, a large number of genetic risk factors have been reported, including the polymorphisms in angiotensin converting enzyme (ACE) (5), methylenetetrahydrofolate reductase (MTHFR) (6), apolipoprotein E (apo E) (7), and paraoxonase (PON) genes (8). ACE converts angiotensin I into angiotensin II, a potent vasopressor peptide, and also inactivates bradykinin (9). The ACE gene has a common insertion/deletion (I/D) polymorphism in intron 16 (5), and the D allele has been associated with CHD and left ventricular hypertrophy in adult populations (9). MTHFR is a key enzyme in the metabolism of homocysteine, and elevated plasma levels of this amino acid have been associated with the development of ATS (10). A relatively common point mutation at nucleotide 677 of the MTHFR gene is responsible for a thermolabile variant of the enzyme that has been associated with increased homocysteine levels (10). Apo E is a polymorphic plasma protein that modulates the metabolism of triglyceride-rich atherogenic lipoproteins (11). A growing body of evidence indicates that apo E polymorphism plays a significant role in the susceptibility to develop ATS; indeed, individuals bearing the 4 allele have higher total cholesterol levels and an increased risk of developing CHD (7). PON is a high-density lipoprotein (HDL)-associated enzy...

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Section: Discussionsupporting

confidence: 92%

Genetic Factors Associated With the Absence of Atherosclerosis in Octogenarians

Zuliani¹,

Cherubini²,

Volpato³

et al. 2002

The Journals of Gerontology Series A: Biological Sciences and M

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“…Studying a population in Belfast who are prone to heart disease, they found that the 2 variant was significantly more common among those over age 90 and the 4 variant frequency was reduced in comparison to people aged 30-65 [57]. A Finnish study found that in looking at centenarians, the incidence of the 2 version of the apolipoprotein gene was 9% among those aged 100-101, 21% for those 102-103, and 25% for those 104 and over [58].…”

Section: Apolipoprotein E (Apoe)mentioning

confidence: 99%

Human Longevity: Nature versus Nurture, Survival versus Mortality~!2010-04-29~!2010-06-30~!2010-08-31~!

Bowirrat¹

2010

TOALTMEDJ

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Numerous studies were published, investigating the associations of ApoE and ACE polymorphisms with longevity. In 1995, we conducted based cross-sectional study among 823 elderly Arab residents in Israel for studying the prevalence and genetics of dementia of Alzheimer's type (DAT). Epidemiological and genes results of (ApoE + ACE) were reported The ApoE frequency was the lowest in the world and no association was found between ACE and DAT. During 2008, we conducted a follow up study looking for survival and mortality rate among the same participants to endeavor if there is any relationship between genes and longevity. The total mortality rate among both genders after thirteen years was 66.34%, and the survival subjects of 88 years or older were 34 persons only out of the initial number 270 in 1995 (34/270 = 12.6%). We used the Chi-Square test to examine the null hypothesis (no difference between observed and expected results): When we compare the survival rate among both sexes in age group (60-74) in 1995 vs. age group (73-87) in 2008. We observed statistically significant high survival rate among males (p=0.003) comparing to females in the same age groups. In contrary, at advanced age, when we compare the survival rate in age group (75-85+) in 1995 vs. age group (88-98+) in 2008, we observed high and significant survival rate among females (p=0.033).Conclusion: High rate of mortality was observed among females in age groups (60-74) in1995 and age group (73-87) in 2008, and high rate of mortality at advanced age was observed among males at advanced age group (75-85+) in 1995 and age group (88-98+) in 2008. More females live longer than men and no association was found between ApoE, ACE genes and longevity, that seems that longevity is exceedingly dependent on other genes in addition to the environmental factors.

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“…Obviously, our genetic makeup plays a major role in our aging process. This has been demonstrated not only in genetic manipulations in worms (4,5) but also in the studies in centenarians and others suggesting that certain genes, such as apolipoprotein E, can be either beneficial or deleterious depending on the isoform we inherit (6)(7)(8)(9)(10)(11)(12)(13)(14). Thus it remains as true today as ever that choosing the right parents before birth remains the best method of ensuring successful aging.…”

mentioning

confidence: 93%