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At least 19 recordsLinked to original sources

[Relationship between blood lipid level and apolipoprotein E gene polymorphism in offspring from longevity and non-longevity families].

OBJECTIVE: To study relationship between genetic factor and level of blood lipid. METHODS: Levels of blood lipid and difference in apolipoprotein E (apo-E) allele frequencies were compared in 86 offspring in seven Uigur longevity families and 62 offspring in nine Uigur non-longevity families and their relationship was explored. RESULTS: After adjustment for age and occupation, blood indicators related to atherosclerosis were all lower in the offspring of longevity families than in non-longevity families, and those correlated inversely with it were higher in the former. Blood levels of triglyceride and apo-B were significant lower (P < 0.05) and the ratio of HDL-ch to LDL-ch was significantly higher (P < 0.05) in male offspring of longevity families than of non-longevity families. The ratio of apo-A to apo-B was significantly higher in female offspring of longevity families than of non-longevity families. Frequency of epsilon4 allele also was significantly fewer in the offspring of longevity families than of non-longevity ones (P < 0.01). Also, analysis showed that individuals with epsilon4 allele had higher levels of serum total cholesterol, lower density lipoprotein cholesterol and apo-B than those with other alleles. CONCLUSION: Average level of blood lipid was better in the offspring of longevity families than that of non-longevity families. apo-E allele polymorphism can in part explain its difference.

Adolescent↗

Immunogenetics of longevity. Is major histocompatibility complex polymorphism relevant to the control of human longevity? A review of literature data.

Literature data suggest that human longevity may be directly correlated with optimal functioning of the immune system. Therefore, it is likely that one of the genetic determinants of longevity resides in those polymorphisms for the immune system genes that regulate immune responses. Accordingly, studies performed on mice have suggested that the Major Histocompatibility Complex (MHC), known to control a variety of immune functions, is associated with the life span of the strains. In the last 25 years, a fair number of cross-sectional studies that searched for the role of HLA (the human MHC) genes on human longevity by comparing HLA antigen frequencies between groups of young and elderly persons have been published, but conflicting findings have been obtained. In fact, the same HLA antigens are increased in some studies, decreased in others and unchanged in others. On the whole, that could lead us to hypothesize that the observed age-related differences in the frequency of HLA antigens are due to bias. In our opinion, this hypothesis is real for most studies owing to major methodological problems. However, some studies that do not meet these biases have shown an association between longevity and some HLA-DR alleles or HLA-B8,DR3 haplotype, known to be involved in the antigen non-specific control of immune response. Thus, HLA studies in man may be interpreted to support suggestions derived from the studies on congenic mice on MHC effects on longevity. However, in mice the association may be by way of susceptibility to lymphomas whereas, in human beings, the effect on longevity is likely, via infectious disease susceptibility. Longevity is associated with positive or negative selection of alleles (or haplotypes) that respectively confer resistance or susceptibility to disease(s), via peptide presentation or via antigen non-specific control of the immune response.

Aging↗

[Comparison of plasma fibrinogen level in members of Uygur family of longevity and non-longevity in Xinjiang].

OBJECTIVE: The associations of plasma fibrinogen level with age in members from longevity families and non-longevity families were compared and the influences of relationship in family members to plasma fibrinogen level were analysed to study the relationship between plasma fibrinogen level and life-span run in family. MEANS: The authors measured fibrinogen in 156 Uygur subjects from 7 longevity families and 9 non-longevity families. RESULTS: Fibrinogen level was relatively stable among different age groups in longevity families. It was an association positively with age in non-longevity. Fibrinogen level of children was closely correlative with parent's. CONCLUSIONS: Genetic factor probably contributes to plasma fibrinogen level. Plasma fibrinogen level correlates with life-span run in family.

Adolescent↗

Parental longevity and polygenic longevity scores in relation to ageing-related factors in a population of 70-year-olds followed over six years: The Gothenburg H70 Birth Cohort Study.

As societies age, a deeper understanding of ageing-related factors that contribute to longevity is needed. We therefore investigated possible longevity factors (social, medical, and biological) in relation to parental longevity (PL) and polygenic longevity scores (PGLSs). We examined 1126 70-year-olds from the Swedish population-based Gothenburg H70 Birth Cohort study in 2014-2016 (response rate 72%), with follow-up in 2019-2022 (response rate 77.6%). Comprehensive examinations included self-reported information on parents' ages, socioeconomic factors, mental, cardiovascular, and neurological health, anthropometry, laboratory data, and genotyping to construct two continuous PGLSs variables (with and without the APOE locus). PL groups were categorised as high if both parents survived to age 85 (17.2%); medium if one parent had survived (43.3%), and low if neither parent had survived to age 85 (39.4%). Higher PL and higher PGLSs were related to less hypertension, higher educational level, better childhood, and current socioeconomic status. In addition, higher PL was associated with higher MMSE score, total cholesterol, HDL-cholesterol (HDL-c) and LDL-cholesterol (LDL-c), lower BMI, homocysteine and inflammatory markers (IL-6, CRP) levels, and less smoking, whereas higher PGLSs was related to less myocardial infarction. At follow-up, high-PL was associated with less increase in plasma pTau217. PGLSs were mainly related to socioeconomic and cardiovascular factors, while individuals with long-lived parents, in addition, had several other characteristics of longevity, such as less inflammation, homocysteine, and markers of dementia. PL may be a proxy for biological ageing and used as a screening for ageing-related disorders in the context of prevention.

APOE↗

Total immediate ancestral longevity (TIAL) score as a longevity indicator: an analysis on Einstein and three of his scientist peers.

The total immediate ancestral longevity (TIAL) score was first introduced by Raymond Pearl as a convenient parameter for quantitating human longevity. TIAL is the summed ages at death of the six immediate ancestors (namely parents and four grandparents) of a propositus. In this communication, I present the calculations of TIAL score for Einstein (1879--1955) and three of his scientist peers, namely Charles Darwin (1809--1882), Irene Joliot Curie (1897--1956) and Aage Bohr (1922--). The TIAL scores for Einstein, Darwin, Irene Curie and Aage Bohr were 390, 378, 372 and 436 respectively. These are markedly lower than 477 reported for Jeanne Calment, the French woman who died in 1997 at the oldest authenticated age of 122 years and 164 days. I conclude that the TIAL score is a convenient and easily quantifiable longevity parameter which anyone interested in determining his or her longevity can use to estimate a tentative number. More light could be shed on the worth of the TIAL score as a longevity indicator, if additional data on the TIAL scores of royalty and celebrities (for whom verified genealogical data are available) are reported.

Biology↗

Genotypes for the cytochrome P450 enzymes CYP2D6 and CYP2C19 in human longevitY. Role of CYP2D6 and CYP2C19 in longevity.

OBJECTIVE: To test whether some genotypes for CYP2D6 or CYP2C19 could contribute to longevity, we genotyped 241 Danish nonagenarians and centenarians for CYP2D6 and CYP2C19. METHODS: For CYP2D6 we identified the alleles CYP2D6*1, CYP2D6*3 and CYP2D6*4 with allele-specific polymerase chain reaction (PCR). The CYP2D6*5 alleles were identified with a long PCR method. For CYP2C19 we identified the alleles CYP2C19*1, CYP2C19*2 and CYP2C19*3 with an oligonucleotide ligation assay. RESULTS: The four alleles for CYP2D6 did not occur in Hardy-Weinberg proportions. The frequency of poor metabolism was slightly higher (10.2%) than expected [7.7%; odds ratio (OR) = 1.36 (0.75-2.40)]. The genotypes for CYP2C19 occur in Hardy-Weinberg proportions. The frequency of poor metabolism (3.8%) was not significantly different from a young control group [3.1%; OR = 1.21 (0.26-5.75)]. CONCLUSION: CYP2D6 could play a role in human longevity due to the lack of Hardy-Weinberg proportions. If CYP2D6 only plays a role in longevity by protecting the poor metabolizers from cancer, we should expect a rise in the frequency in these genotypes in Denmark from 7.7% among young adults to 10-11% among very old people. We found a frequency of poor metabolism of 10.2% in the very old group. CYP2C19 is - due to the occurrence of Hardy-Weinberg proportions and the expected number of poor metabolizers unlikely to contribute to human longevity.

Adult↗

Implications for the insulin signaling pathway in Snell dwarf mouse longevity: a similarity with the C. elegans longevity paradigm.

Mutation analyses in the nematode, Caenorhabditis elegans, and mice have identified genes that increase their life-span via hormonal signal transduction, i.e. the insulin/insulin-like growth factor-1 (IGF-1) pathway in nematodes, and the growth hormone (GH)-thyriod stimulating hormone (TSH)-prolactin system in Snell dwarf mouse mutants. We have shown that the GH deficiency due to Pit1 mutation in the long-lived Snell dwarf mice may decrease circulating insulin levels, thereby resulting in a decreased activity of the insulin/IGF-1 signaling pathway. The data presented are consistent with our hypothesis that the decreased circulating insulin levels resulting from the Pit1 mutation mimics a physiological state similar to that proposed to occur in the long-lived C. elegans, daf-2 mutant. Our studies demonstrate a series of changes in components of the insulin/IGF-1-signaling pathway that suggest a reduction-of-function of this pathway in the aged dwarf. These include a decreased IRS-2 pool level, a decrease in PI3K activity and its association with IRS-2 and decreased docking of p85alpha to IRS-2. Our data also suggest a preferential docking of IRS-2-p85 alpha -p110 alpha in the aged dwarf liver and IRS-2-p85 alpha -p110 beta in the aged control. We speculate that the preference for the p110 alpha-containing complex may be a specific characteristic of a downstream segment of the longevity-signaling cascade. We conclude that the Pit1 mutation may result in physiological homeostasis that favors longevity, and that the Snell dwarf mutant conforms to the nematode longevity paradigm.

Aging↗

Statistico-demographic investigations on the longevity of the Romanian population. II. Longevity and the process of demographic aging.

This is the second part of a two-part paper concerning longevity in Romania. In this part the authors examine "the extent to which levels of longevity reached in the Romanian counties over the period 1966 and 1968 were the result of...demographic aging; to this aim the nature and intensity of the relationship between the dynamics of longevity and demographic aging indices by county, sex and social background [were] correlatively analysed." (SUMMARY IN FRE AND RUM)

Adult↗

Effect of temperature on longevity and productivity in Drosophila ananassae: evidence for adaptive plasticity and trade-off between longevity and productivity.

The genetic response of body size to temperature in the laboratory provides an interesting example of phenotypic plasticity. We found that females of Drosophila ananassae reared to adulthood at 18 degrees C showed significant increase in body weight as compared to females reared at 25 degrees C. At a given temperature, early productivity and lifetime productivity were the highest when the rearing and test temperature were the same. The effect of test temperature was highly significant for total productivity and early productivity. The interaction between test temperature and development temperature was also highly significant. Effect of development temperature was not significant. The females reared at 18 degrees C showed greater body weight but their productivity was not significantly higher than smaller females reared at 25 degrees C. Thus, the usually close relationship between size and fecundity is lost when the size change is due to rearing temperature. These findings provide evidence for adaptive plasticity in D. ananassae. We also found a negative correlation (trade-off) between longevity and productivity, the first report of such a trade-off between longevity and productivity in D. ananassae.

Adaptation, Physiological↗

Body composition and longevity: is there a longevous morphotype?

Life expectancies are increasing in populations throughout the world. As infectious diseases decline as causes of mortality, certain degenerative diseases including cardiovascular disease and cancer account for an increasing percentage of deaths. As more people survive into old age, the intrinsic limits on the human life span will be reached. It is clear that genetic factors have a strong influence on the life span. It is not clear, however, that there are identifiable longevous body types (morphotypes). For the first time in human history, large numbers of people 80 years old and older are available for study. If there is an association between body form and composition and superior longevity, it should be possible to identify its major aspects. Monitoring changes in body composition throughout the life cycle and the retention of reserves to be drawn upon when disease or trauma threaten life may provide the basis for prediction of the course of life threatening diseases. The unusually high survival of morphotypes classifiable as "moderately obese" casts doubt on standards recommending "ideal weights for height" if the criterion in question is survival.

Adipose Tissue↗

A look at the basic correlates of longevity: is longevity a superficial trait?

Nature appears to have distributed life spans, whether long or short, entirely upon the possession or non-possession of a few physiologically superficial characteristics, namely, immunity of mature, full-sized specimens from the effects of: (1) predation, (2) competition, (3) fire, (4) disease, and (5) the existence of a definite usefulness for long life spans in bridging lengthy periods unfavorable to the reproduction and/or maturation of offspring. Extremely strong correlations are presented in proof of the above relationships. Since longevity mechanisms can closely correlate to superficial traits, it is unlikely that they comprise an integral part of basic structural or biochemical processes. In the case of trees, all five of the above traits are apparently required for the achievement of potential life spans in excess of 1000 years. By contrast, the longest live animal species appear to fully possess only (1) and (3) of the five prerequisite traits above. This observation may fully account for the fact that maximum life spans of trees are 30-40 times greater than those of the longest lived animals.

Animals↗

Successful selection for increased longevity in Drosophila: analysis of the survival data and presentation of a hypothesis on the genetic regulation of longevity.

Long lived strains of Drosophila melanogaster have been generated via 25 generations of artificial selection. The mean and the maximum lifespans have been increased both absolutely as well as relative to the controls. The mean lifespan of the selected line now exceeds the maximum lifespan of the controls. The data shows that this increase is entirely accounted for by a genetically based delay in the onset of senescence. Identification and analysis of biomarker data involving reproductive functions supports this interpretation and leads to a suggestion of the processes involved in the lifespan extension. This increase in the duration of the pre-senescent period is under both genetic and environmental control. Senescence itself is not under genetic control and appears to occur stochastically. Selection for decreased longevity was unsuccessful, supporting the concept of a minimum species specific lifespan. A testable hypothesis regarding the biphasic mode of gene regulation of senescence is presented in which a gene-environment interaction takes place in larval life that results in a temporal reprogramming of other, presumably structural, genes which act in adult life at a time prior to the onset of senescence.

Aging↗