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Published on: September 17, 2020
Vascular genetic factors and human longevity
Francesco Panza1, Alessia D'Introno, Anna M Colacicco
1Department of Geriatrics, Center for Aging Brain, Memory Unit, University of Bari, Policlinico, Piazza Giulio Cesare, 11-70124 Bari, Italy. geriat.dot@geriatria.uniba.it
Insights
Investigating genetic factors in centenarians reveals apolipoprotein E (APOE) concentration may influence longevity. Regional variations in genes like angiotensin I converting enzyme 1 (ACE1) also suggest complex genetic roles in exceptional lifespan.
Area of Science:
- Genetics and Longevity Research
- Molecular Biology and Aging
- Cardiovascular and Neurological Disease Genetics
Background:
- Complex interrelationships exist between age-associated illnesses like vascular disease and Alzheimer's disease (AD).
- Lipoprotein metabolism and vascular genetic risk factors are implicated in human longevity.
- Previous studies noted higher frequencies of the apolipoprotein E (APOE) epsilon4 allele in middle-aged individuals compared to centenarians.
Purpose of the Study:
- To examine biological and genetic pathways in centenarian populations for insights into human longevity.
- To investigate the role of apolipoprotein E (APOE) levels and alleles in relation to aging and lifespan.
- To review genetic vascular factors potentially involved in exceptional human longevity.
Main Methods:
- Analysis of apolipoprotein E (APOE) allele frequencies in centenarian and middle-aged populations.
- Examination of serum APOE levels across different APOE genotypes (epsilon2, epsilon4) and their association with age, adjusted for HDL cholesterol.
- Review of studies on other genetic factors (e.g., ACE1, MTHFR, APOA-I) implicated in vascular risk and longevity.
Main Results:
- Consistent findings show a higher frequency of the APOE epsilon4 allele in younger individuals compared to centenarians.
- A trend of reduced serum APOE levels from APOE epsilon2 to epsilon4 carriers was observed, with significant age-related differences in epsilon4 carriers after HDL adjustment.
- Replication of increased angiotensin I converting enzyme 1 (ACE1) D allele prevalence in French centenarians was not consistently found, suggesting regional genetic variations.
Conclusions:
- APOE concentration may serve as a potential longevity factor, although further studies are needed for confirmation.
- Regional differences in the frequency of genetic variants like APOE and ACE1 may influence longevity across European populations.
- This review highlights the complex interplay of genetic vascular factors in determining human longevity.
Abstract:
Complex inter-relationships between age-associated illnesses, such as vascular disease and Alzheimer's disease (AD), suggest that biological and genetic pathways may be worthy of examination in centenarian populations to provide insights into human longevity. This is also borne out by the involvement of lipoprotein metabolism and a number of vascular genetic risk factors. Repeated findings of a higher frequency of the apolipoprotein E (APOE) epsilon4 allele in middle-aged subjects compared with centenarians were reported. Furthermore, we have also shown how in different populations there is a significant trend in reduction of serum APOE levels from APOE epsilon2- to epsilon4-carrier as well as significant differences in serum APOE levels respect to age in epsilon4-carriers but only after adjustment for HDL cholesterol. In contrast, findings of increased prevalence of the angiotensin I converting enzyme 1 (ACE1) D allele in French centenarians have not been replicated, suggesting the possibility that regional differences may occur in ACE1(*)D frequency within Europe in centenarians, as has been recently reported for APOE epsilon2 and epsilon4 alleles. A number of studies have examined the potential role in longevity of other genes involved in vascular risk, haemostasis, and blood pressure regulation [methyltetrahydrofolatereductase (MTHFR), apolipoprotein A1 (APOA-I), apolipoprotein C3 (APOC-III), apolipoprotein A4 (APOA-IV), paraoxonase 1 (PON1), plasminogen activator inhibitor type I (PAI-1)], with contrasting results. While further studies are needed to confirm the possible role of APOE concentration as putative longevity factor, this paper provides an overview of genetic vascular factors potentially involved in human longevity.
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