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Four families highly clustered for extreme longevity are described here, representing the first report of clustering for this phenotype. Families such as these may prove to be helpful in the further understanding of the genetic contribution to achieving exceptional longevity.
Aging of population in Tyumen region and a growing number of long livers, marked in last decade, make research of medical and social aspects of this age persons actual. Complex examination of 84 persons (age 90-102 years) was made. High longevity of parents, absence of chronic internal diseases complications in them, mechanisms of adaptation to severe climatic conditions due to the long living in Tyumen region are important factors for determination of longevity phenomenon.
Present knowledge on the effects of growth hormone (GH)/insulin-like growth hormone (IGF)1 deficiency on ageing and lifespan are reviewed. Evidence is presented that isolated GH deficiency (IGHD), multiple pituitary hormone deficiencies (MPHD) including GH, as well as primary IGE1 deficiency (GH resistance, Laron syndrome) present signs of early ageing such as thin and wrinkled skin, obesity, hyperglycemia and osteoporosis. These changes do not seem to affect the lifespan, as patients reach old age. Animal models of genetic MPHD (Ames and Snell mice) and GH receptor knockout mice (primary IGF1 deficiency) also have a statistically significant higher longevity compared to normal controls. On the contrary, mice transgenic for GH and acromegalic patients secreting large amounts of GH have premature death. In conclusion longstanding GH/IGF1 deficiency affects several parameters of the ageing process without impairing lifespan, and as shown in animal models prolongs longevity. In contrast high GH/IGF1 levels accelerate death.
The author has divided his work into parts. The first part entitled "Premature Death of Physicians" is dedicated to those who started their research, scientific works and fruitful medical practice but the premature death has stopped their lives and activities. Death causes are presented in ten chapters (groups of causes), i.e. Tuberculosis - Other Lung Diseases - Heart and Vessel Diseases - Septicaemiae - Infectious Diseases in Subgroups: Typhus, Plague, Cholera, Yellow Fever, Diphtheria, Influenza, Malaria, Smallpox, etc. - Encephalopathies and Mental Diseases - Malignant Neoplasms - Noninfectious Unit Diseases - Accidents - Manslaughters - Death Sentences - Suicides - Not Settled Causes of Death. There are in total 283 biographies in the first part. The second part "Longevity of Physicians" is much longer than the first one and contains 509 biographies of doctor, scientists, research workers and practitioners, meritorious in the history of medicine who attained at least 80 years of age. The biographies are arranged in 22 chapters, one for every year from 80 years of age assumed as the beginning of longevity up to 104 years in one of the cases. In each chapter the biographies are arranged in the alphabetical order. In the Epilogue the author presents shortly his conclusions and observations related to the first part and wider commentaries for the second part.
BACKGROUND AND OBJECTIVES: In general, elderly patients with Hodgkin's lymphoma (HL) have a less favorable prognosis than younger patients. Factors such as inadequate therapy often due to decreased tolerance to treatment, presence of intercurrent diseases and accumulation of certain clinical and biological risk factors contribute to the poor outcome. Established predictors of prognosis in HL are less appropriate in the elderly population. Consequently, there is a need for additional markers to guide treatment decisions and to improve prediction of outcome. In the general population, the expected length of life of an individual is intimately associated with that of his/her parents. In a small cohort of elderly HL patients, we had previously observed high familial life-span of two previous generations predicts superior survival. The aim of this study was to test the hypothesis that parental longevity alone--an easily accessible and non-disease associated variable--is also associated with improved outcome using an enlarged series of elderly HL patients. DESIGN AND METHODS: One hundred and twenty-one patients with HL >60 years at diagnosis were included. The median follow-up time was 67 (range 37-175) months. Data regarding age at death and reported cause of death were available through parish offices for 228 (94%) parents. The effect of parental lifespan on HL survival included the use of Kaplan-Meier curves and Cox' proportional hazards regression analysis. RESULTS: Maternal as well as paternal lifespan correlated poorly with HL survival, both with regard to overall and disease-specific survival. There was, however, a tendency towards a decreased risk of dying among patients with low maternal lifespan (all-cause mortality: RR=0.7, 95% CI 0.5-1.0). INTERPRETATION AND CONCLUSIONS: Parental longevity does not predict superior survival in elderly patients with HL.
Currently two types of theories of aging are generally recognized: the genetic and the free radical theories. Each of them allow to explain plasibly some particular features of the aging process and pathologies associated with it. However, there are some phenomena related to aging and longevity that are not easily interpreted in frames of both theories; in particular, the increase of the life span of animals following caloric restriction, or beneficial effects of reactive oxygen species on multiple living functions, etc. On the other hand, the mostly unknown principles of theoretical biology suggested by E.S. Bauer in 1930s allow to explain from the monistic basis the essence of those and many other phenomena related to development, aging and longevity. The major postulates of the Bauer's theory and the corollaries of them are reviewed with the emphasis on the specifically biological phenomenon discovered by Bauer, the so called "Basic Process". The latter allows to find the means for the significant extension of the active life span. Taking Bauer's principles into consideration we contemplate the modern data on the peculiarities of free radical processes in living systems giving rise to electron excited species generation as the energy-informational foundation for the build up of an organism's resources for the counteraction of most pathological factors. The needfulness to employ these considerations for the resolution of the problems of gerontology is substantiated.
"Based on the author's long and in-depth social investigations in Bama County, Guangxi Zhuang Autonomous Region, [China], one of the world's well-known longevity zones, this article looks at the longevity group and the favorable environment for their survival in an attempt to gain a better understanding of the issue both theoretically and empirically."
TO IDENTIFY THE GENETIC FACTORS: Family and twin studies showed that longevity results from the interaction of genetic and environmental factors. Despite progress the performed made in the study of animal models highlighting some interesting metabolic pathways, characterization of genetic factors remains difficult in human beings. Two genetic approaches are currently available: association studies and sib-pair analyses. ASSOCIATION STUDIES: The first method is based on the comparison of polymorphism repartitions on candidate genes in two matched populations of old people and young controls. SIB-PAIR ANALYSES: The second requires genotyping of brothers and/or sisters on a set of highly polymorphic markers, in order to identify new candidate regions on the genome. APOE: Until now, the only gene that remains clearly associated with longevity is the Apolipoprotein E gene.
A PROBABLE ROLE: The great increase in life expectancy over the past decades and too short a time lapse for any major genetic mutations to intervene, are arguments in favour of the intervention of environmental factors in longevity. A FAIRLY LONG LIST: Various environmental factors can be envisaged: prenatal environment, pollution, radiation and oncogenic agents, notably tobacco, food (quantitatively and qualitatively), medicinal products, stress, education and socio-professional life style, isolation, number of children and sexual activity, sports and exercising, etc. It is highly likely that all these factors, or at least some of them, have a real effect on longevity, although this is difficult to demonstrate directly. A COMBINED EFFECT: The basic idea of this paper is that these environmental factors should be seen as agents, the effects of which would be combined with those of genetic factors, considered as agents of radically different nature. We suggest that, in order to have any real effect, these environmental factors have to work on the same cell mechanisms as those that affect the genetic process, notably the mechanisms related to oxidative stress and genetic expression.
OBJECTIVE: To explore the distribution of I/D polymorphisms of angiotensin converting enzyme (ACE) gene and its relation to natural longevity in the Xinjiang Uygur people. METHODS: Polymerize chain reaction, single strand conformation polymorphism, and direct sequencing technique were used to test the I/D polymorphisms of ACE gene in 42 centenarians, 102 people aged 90-99, 70 people aged 65-70, 53 cases of natural death aged 65-70 were used as controls. RESULTS: The frequencies of ACE genotypes DD, DI, and II were 28.6%, 30.9%, and 40.5% respectively in the centenarian group, the frequency rates of D and I alleles were 0.44 and 0.56. The frequency rate of D/D genotype of the centenarian group was significantly higher than that of the group aged 65-70 (28.6% vs. 12.9%, chi2 = 4.25, P < 0.05), however, not significantly different from that of the group aged 90 (P > 0.05). The frequency rate of D allele of the group of centenarian was significantly higher than that of the group aged 65-70 (44.0% vs. 36.4%, chi2 = 4.47, P < 0.05). The frequency rates of genotype D/D and D alleles were significantly higher in the centenarian group than in the controls (both P < 0.01). CONCLUSION: ACE gene polymorphism is closely correlated with life span of individuals. Longevity is the result of pleiotropic age-dependent influence of multiple factors.
The functional polymorphism methionine synthase (MTR) c.2576A-->G (D919G) influences homocysteine and folate metabolism and has been reported to be of protective function against oncological, neurodegenerative and vascular diseases. We analyzed 329 healthy individuals to confirm whether this polymorphism might be of epidemiological impact on disease-free longevity. In our sample, prevalence of the G-allele was significantly higher in the older than in the younger individuals (p=0.005) supporting the thesis that MTR c.2576A-->G is beneficial to disease-free longevity. Separate analysis of female and male subjects revealed that the influence of the MTR genotype on male subjects became relevant at a younger age as opposed to female subjects suggesting a gender-dependent effect.
Longevity assurance genes (LAGs) represent a subgroup of the homeobox gene family. Five mammalian homologs have been reported, and the corresponding proteins have previously been investigated with respect to their key role in ceramide synthesis. However, members of the LAG family have been shown to be involved in cell growth regulation and cancer differentiation. In an effort to characterize additional members of the LAG family, we have screened the latest releases of genomic databases and report on the bioinformatic characterization of yet another member, LAG1 longevity assurance homolog 6 (LASS6). Like other LAG family members, the LASS6 protein contained a homeodomain and LAG1 domain. In phylogenetic analyses, it displayed highest homology to LASS5. The corresponding gene was localized to human chromosome 2q24.3, spanning a rather large genomic region of 318 kb. Orthologous sequences in mouse and zebrafish suggested a conservation of LASS6 in vertebrates as the protein and corresponding genomic sequences were highly conserved. LASS6 expression was analyzed in silico, and the gene was shown to be broadly expressed in a wide range of tissues. Furthermore, available microarray data suggested a role in cancer differentiation and early embryonic development.
Longevity and morbidity and death from myocardial infarction were examined in eight kindreds with familial hypobeta lipoproteinemia and in 18 kindreds with familial hyperalpha lipoproteinemia. Expectation of life for males and females from kindreds with hypobeta lipoproteinemia was 9 and 12 years longer (p less than or equal to 0.002) than that indicated by population statistics for U.S. white populations, whereas expectation of life for males and females from kindreds with hyperalpha lipoproteinemia was 5 and 7 years longer (p less than 0.02). Morbidity from myocardial infarction in 115 living first-degree adult relatives of probands with hypobeta and hyperalpha lipoproteinemia and in 364 living first-degree adult relatives of normolipemic spouse controls were compared. Nonfatal myocardial infarction (MI) was reported for 18 of 364 (5 per cent) relatives of normal spouse controls and in 0 of 115 relatives of hypobeta and hyperalpha subjects (p less than 0.05). The ratios (mean+/-S.E.) of C-LDL to C-HDL in familial hypobeta and hyperalpha lipoproteinemia were 0.79+/-0.06 and 1.21+/-0.06, as compared to 2.41+/-0.12 in a control population (p less than 0.001). If high-density lipoproteins confer protection against development of atherosclerosis, whereas low-density lipoproteins have opposite effects, then we speculate that the low ratio of C-LDL:C-HDL may be related to prolonged longevity and decreased morbidity from myocardial infarction in familial hypobeta and hyperalpha lipoproteinemia.
The burden of human suffering and the costs of money, manpower and material for the treatment and maintaining of disabled and/or chronically ill--particularly ageing and old--people are increasing immensely. Primary prevention--if possible--is therefore urgently needed in this field of health and social care. Prospective longitudinal epidemiological research may provide an important tool to learn more and better about the causes and development of many processes of malfunctioning and the incidence of disabling conditions at higher ages. For several reasons not many major extensive surveys of this kind have been undertaken so far, although a few are now underway. A very brief overview is presented of some main follow-up surveys, primarily where predictors of disability and longevity are involved. Comparability is difficult, results are sometimes conflicting. Good objective health, high scores on certain intelligence and memory tests seem to be good predictors for longevity, good subjective health more or less. In a Dutch survey disabilities with respect to activities of daily life were more strongly related to survival time in women than in men. Some variables indicating the use of health care services correlated all negatively with survival. The complexity of variables to predict better at high age the risks of disabilities, and survival time, requires a.o. sophisticated longitudinal studies, upon the results of which to base an adequate policy response.
The life spans of parents and children appear only weakly related, even though parents affect their children's longevity through both genetic and environmental influences. These influences can be summarized as a correlation between parents' and children's frailty. It is shown that even if children perfectly inherit their frailty from their parents, parents' life spans explain little of the variance in children's life spans, because the variance in life expectancies among people with different frailties is small compared with the variance in life spans among people at the same level of frailty. By interpreting frailty as a relative risk in a proportional-hazard model, longevity as a duration or waiting time, and inheritance as an invariance in relative risk over time, one can extend this result to repeatable events involving fertility, migration, marriage, unemployment, and so forth.
Ageing in Drosophilia is modified according to their physiological state. Adult longevity is decreased by sexual activity: in both sexes the life span of virgins is higher. For the same physiological state male longevity is always lower than that of females.
The effects of salinity, pH, and temperature on the longevity and hatchability of miracidia of Philophthalmus megalurus and P. gralli were determined. Miracidia of both species are able to hatch and survive at saline concentrations much above physiological levels, although these processes are reduced in 2.0--2.4% saline and completely inhibited at 2.6%. The greatest hatching rates for both species were found near neutrality (pH 6--8) but some miracidia hatched at the extreme pH levels of 3 and 12. Philophthalmus megalurus miracidia exhibited longer half-lives under acid conditions (pH 2--6) than P. gralli miracidia; conversely, P. gralli miracidia showed longer half-lives in alkaline conditions (pH 8--11). Hatching and longevity were much greater below room temperature (5--20 C) than above (30--50 C) for miracidia of both species. Temperatures above 50 C proved lethal for eyefluke eggs. Except in acid pH, P. gralli miracidia showed longer half-lives than miracidia of P. megalurus. Comparison to studies on schistosomes revealed that the inhibitory effects of physiological saline and host body temperature on the hatching process of schistosome eggs does not occur in these 2 species of eyeflukes.
The effect of food restriction in rats to a level 46% below the intake of those fed ad libitum was studied in relation to onset of disease and longevity. Dietary restriction at this level kept adult rats in a nutritional state short of the development of excess body fat, and had little effect on skeletal growth or sexual maturity. Onset of microscopically observed renal, vascular, myocardial and skeletal muscle lesions, as well as mammary fibroadenoma in females, was delayed and resulted in greater longevity. Life expectancy of male rats was increased by 25% and of females by 39%. Time of onset of disease appears to be regulated by a common factor which is influenced by dietary intake.