Human longevity and common variations in the LMNA gene: a meta-analysis

A mutation in the LMNA gene is responsible for the most dramatic form of premature aging, Hutchinson-Gilford progeria syndrome (HGPS). Several recent studies have suggested that protein products of this gene might have a role in normal physiological cellular senescence. To explore further LMNA's possible role in normal aging, we genotyped 16 SNPs over a span of 75.4 kb of the LMNA gene on a sample of long-lived individuals (LLI) (US Caucasians with age ≥ 95 years, N=873) and genetically matched younger controls (N=443). We tested all common nonredundant haplotypes (frequency ≥ 0.05) based on subgroups of these 16 SNPs for association with longevity. The most significant haplotype, based on four SNPs, remained significant after adjustment for multiple testing (OR=1.56, P=2.5 × 10(-5) , multiple-testing-adjusted P=0.0045). To attempt to replicate these results, we genotyped 3619 subjects from four independent samples of LLI and control subjects from (i) the New England Centenarian Study (NECS) (N=738), (ii) the Southern Italian Centenarian Study (SICS) (N=905), (iii) France (N=1103), and (iv) the Einstein Ashkenazi Longevity Study (N= 702). We replicated the association with the most significant haplotype from our initial analysis in the NECS sample (OR=1.60, P=0.0023), but not in the other three samples (P > 0.15). In a meta-analysis combining all five samples, the best haplotype remained significantly associated with longevity after adjustment for multiple testing in the initial and follow-up samples (OR=1.18, P=7.5 × 10(-4) , multiple-testing-adjusted P=0.037). These results suggest that LMNA variants may play a role in human lifespan.     

Genomics of human longevity

In animal models, single-gene mutations in genes involved in insulin/IGF and target of rapamycin signalling pathways extend lifespan to a considerable extent. The genetic, genomic and epigenetic influences on human longevity are expected to be much more complex. Strikingly however, beneficial metabolic and cellular features of long-lived families resemble those in animals for whom the lifespan is extended by applying genetic manipulation and, especially, dietary restriction. Candidate gene studies in humans support the notion that human orthologues from longevity genes identified in lower species do contribute to longevity but that the influence of the genetic variants involved is small. Here we discuss how an integration of novel study designs, labour-intensive biobanking, deep phenotyping and genomic research may provide insights into the mechanisms that drive human longevity and healthy ageing, beyond the associations usually provided by molecular and genetic epidemiology. Although prospective studies of humans from the cradle to the grave have never been performed, it is feasible to extract life histories from different cohorts jointly covering the molecular changes that occur with age from early development all the way up to the age at death. By the integration of research in different study cohorts, and with research in animal models, biological research into human longevity is thus making considerable progress.     

Number of siblings and children of short and long living individuals

The work aimed at grasping eventual relations between the grandparents' life length and the number of their siblings and children. A poll of 2800 students of Wroclaw higher education institutions (1023 men and 1777 women) from 18 to 26 years of age was conducted. Information concerning the number of siblings and children of the examined students' grandparents, and in case of the dead—their age at the moment of death, were used. The material was divided into two categories (using death—rate tables and death age median: short living (SL) and long living (LL). The examined relations were analyzed separately for mothers' mothers (MM), fathers' mothers (FM), mothers' fathers (MF) and fathers' fathers (FF) of the students combined these groups were also analysed. Number of siblings in the families of grandparents of the same categories of longevity generally doesn't differ significantly for each group of grandparents. Short living grandparents have significantly fewer siblings than the long living ones. Number of children, similarly as the number of siblings, is also higher in case of long living individuals. The described relation shall probably be sought in the so—called protective role of the family.     

Long lifespans have evolved with long and monounsaturated fatty acids in birds

The evolution of lifespan is a central question in evolutionary biology, begging the question why there is so large variation among taxa. Specifically, a central quest is to unravel proximate causes of ageing. Here, we show that the degree of unsaturation of liver fatty acids predicts maximum lifespan in 107 bird species. In these birds, the degree of fatty acid unsaturation is positively related to maximum lifespan across species. This is due to a positive effect of monounsaturated fatty acid content, while polyunsaturated fatty acid content negatively correlates with maximum lifespan. Furthermore, fatty acid chain length unsuspectedly increases with maximum lifespan independently of degree of unsaturation. These findings tune theories on the proximate causes of ageing while providing evidence that the evolution of lifespan in birds occurs in association with fatty acid profiles. This suggests that studies of proximate and ultimate questions may facilitate our understanding of these central evolutionary questions.     

Longevity of hibernating queens in Vespa orientalis (Hymenoptera: Vespinae)—Effects of physical and chemical treatments

Young queens of V. orientalis collected from nests in the field at the end of the season, just before the hornets naturally enter hibernation, were evaluated for longevity under varying laboratory conditions. Queens kept under full illumination and heating had a briefer life span than did queens kept under full illumination alone or under complete heating alone. All, however, were shorter lived than control queens kept under the thermal and photoperiodic conditions prevailing at that time in nature. Feeding of theophylline to the queens caused them to emerge from hibernation and succumb to an early death. Feeding of allopurinol to the queens diminished their activities relative to control queens but did not abbreviate their life span compared to the control queens.     

Comparative biochemical and stress analysis of genetically selected drosophila strains with different longevities

We have performed a comparative analysis of the effects of age of reproduction on the biochemical (protein, lipid, and glycogen content) and stress resistance (ability to survive starvation, desiccation, and exogenous paraquat) parameters on 10 sister lines of five different Drosophila strains. Four pairs of these sister lines were selected under different regimens for either early or delayed reproduction; the fifth pair was maintained in a nonselected state and served as the baseline strain to which all others were compared. It is generally accepted that the early regimens give rise to short-lived phenotypes, whereas the delayed regimens give rise to long-lived phenotypes. Our results suggest that a mechanism involving lipid and starvation resistance is not operative in our long-lived strains. In addition, a mechanism involving glycogen content and desiccation resistance is only weakly supported. Finally, there is strong support for a mechanism that gives rise to enhanced paraquat resistance and therefore may involve regulatory changes in the pattern of ADS gene expression. In addition, the 15-day early age at reproduction regimen (M type) shows qualitatively similar responses to that of the late age at reproduction regimen (L type). These results suggest that correlations between biochemical traits and longevity must be interpreted with caution. We discuss possible reasons for these results, including the possibility of multiple mechanisms, each leading to a different extended longevity phenotype.     

The co‐occurrence of mtDNA mutations on different oxidative phosphorylation subunits,not detected by haplogroup analysis,affects human longevity and is population specific

To re‐examine the correlation between mtDNA variability and longevity, we examined mtDNAs from samples obtained from over 2200 ultranonagenarians (and an equal number of controls) collected within the framework of the GEHA EU project. The samples were categorized by high‐resolution classification, while about 1300 mtDNA molecules (650 ultranonagenarians and an equal number of controls) were completely sequenced. Sequences, unlike standard haplogroup analysis, made possible to evaluate for the first time the cumulative effects of specific, concomitant mtDNA mutations, including those that per se have a low, or very low, impact. In particular, the analysis of the mutations occurring in different OXPHOS complex showed a complex scenario with a different mutation burden in 90+ subjects with respect to controls. These findings suggested that mutations in subunits of the OXPHOS complex I had a beneficial effect on longevity, while the simultaneous presence of mutations in complex I and III (which also occurs in J subhaplogroups involved in LHON) and in complex I and V seemed to be detrimental, likely explaining previous contradictory results. On the whole, our study, which goes beyond haplogroup analysis, suggests that mitochondrial DNA variation does affect human longevity, but its effect is heavily influenced by the interaction between mutations concomitantly occurring on different mtDNA genes.     

The influence of salinity on the cercariae of three species of Schistosoma

Donnelly F. A., Appleton C. C. and Schutte C. H. J. 1984. The influence of salinity on the cercariae of three species of Schistosoma. International Journal for Parasitology14: 13–21. The effect of salinity on the longevity and infectivity of cercariae of Schistosoma mattheei, Schistosoma haematobium and Schistosoma mansoni was determined. No significant differences in cercarial longevity occurred (p > 0.05) in low salinities (0–5.25%), whereas further increases in salinity resulted in progressive decreases in survival. In salinities ? 17.5%, cercariae were incapable of surviving for longer than 11 min. A maximum life-span of up to 122 h was recorded for some S. mattheei cercariae. Cercarial infectivity, as indicated by worm returns, was reduced progressively with increasing salinity up to a lethal limit of 10.5%. Differences in the salinity tolerance of the cercariae of the three species were discussed.     

西方长寿与衰老研究史精要

长寿是一个美丽的梦想,衰老是一个神秘的谜团.旨在回顾西方文明从远古至20世纪初,从民间到学术界,探索长寿之路,破解衰老之谜,冥思苦想苦苦追寻的漫漫历程,并按历史的足迹,将这错综复杂的过程分为八个历史时期予以阐述.     

Longevity of seven species of cactophilic Drosophila and D. melanogaster on carbohydrates

Adults of 6 species of Drosophila that use decaying prickly pear cactus (Opuntia sp.) as breeding and feeding sites were compared to each other and to D. nigrospiracula, whose host is saguaro cactus, and to the cosmopolitan D. melanogaster, in their utilization of 21 sugars for longevity (time to 50% mortality). In general, the utilization of sugars by these flies for longevity followed the pattern observed with the other insects. None of the species were able to live very long on solutions of pentoses, uronic acids, inositol, rhamnose, sorbose or the β-linked disaccharides, lactose and cellobiose. Althogh all could use glucose, fructose, sucrose, maltose and melezitose well, their life spans on galactose, mannose, trehalose and raffinose were more variable. Two of the Opuntia feeders were also tested on a number of other carbohydrates. Ribitol, mannitol, sorbitol and xylitol significantly prolonged the life of D. arizonensis but not that of D. wheeleri. Neither species lived long on solutions of arabitol, galactitol, starch, inulin or on arabogalactan.     

The effect of reproductive activity on the longevity of male Drosophila melanogaster is not caused by an acceleration of ageing

Male D. melanogaster kept supplied with virgin females had lower longevity than males kept without access to females. Cessation of reproductive activity by males previously kept with females resulted after a short lag in the same life expectancy as that of flies of the same age which had never had females. Commencement of reproductive activity resulted in life expectancy indistinguishable from that of males of the same age kept with females throughout life. The effect of reproductive activity on longevity is therefore short-term and reversible and not due to an acceleration of ageing. This finding has implications for the way that different theories of the evolution of ageing should be tested.     

Can FSH influence longevity?

It was recently reported that the extragonadal actions of follicle‐stimulating hormone (FSH) include regulation of brown and white adipose tissue function and thermogenesis. Based on these findings and on our evidence for reduced FSH levels and enhanced thermogenesis in long‐lived growth hormone (GH)‐deficient mice and GH‐resistant mice, we suggest that FSH may have a role in the control of aging and longevity. We speculate that alterations in FSH secretion may represent one of the mechanisms of trade‐offs between reproduction and aging.     

Is there an adverse effect of sons on maternal longevity?

Recent years have witnessed the emergence of a literature examining the effects of giving birth to sons on postmenopausal longevity in pre-industrial mothers. The original paper in this lineage used a sample (n=375) of Sami mothers from northern Finland and found that, relative to daughters, giving birth to sons substantially reduced maternal longevity. We examine this hypothesis using a similar and a much larger sample (n=930) of pre-industrial Sami women from northern Sweden, who in terms of their demographic, sociocultural and biological conditions, closely resemble the original study population. In contrast to the previously reported results for the Sami, we find no evidence of a negative effect of sons on maternal longevity. Thus, we provide the most compelling evidence to date that the leading result in the literature must be approached with scepticism.     

Apoptosis-related mitochondrial dysfunction defines human monocyte-derived dendritic cells with impaired immuno-stimulatory capacities

The death of dendritic cells (DCs) can potentially influence immune responses by affecting the duration of DC stimulation of lymphocytes. Here, we report that cultured mature monocyte-derived DCs manifest early mitochondrial damage ( i.e. within 24 hrs), characterized by mitochondrial membrane potential (ψΔm) disruption and mitochondrial release of pro-apoptotic factors, followed by reactive oxygen species (ROS) production and activation of caspases. Afterwards, DCs with mitochondrial alterations are condemned to undergo apoptosis and necrosis. Macroarray analysis results (validated by real time quantitative-PCR (QRT-PCR) and immunoblotting), showed up-regulation of the pro-apoptotic member of the Bcl-2 family, Bim, while expression of several anti-apoptotic molecules was down-regulated. Importantly, pre-apoptotic DCs (characterized by a low Δψm) showed a modified phenotype, with down-regulation.of HLA-DR and of the co-stimulatory molecules CD80 and CD86. Moreover, sorted viable low ψΔm DCs were unable to activate allogeneic T cells, indicating that pre-apoptotic DCs have already lost some of their immuno-stimulatory capabilities long before any detectable signs of death occur. Perturbations to mitochondrial respiration with rotenone identified the same modifications to DC immune functions. These data indicate a strong requirement for mitochondrial integrity for the immuno-stimulatory capacities of DC. Determining ΔΨm could be a useful parameter to select 'fully' functional DCs for anti-tumour vaccines.     

草地螟阿格姬蜂生物学特性初步研究

草地螟阿格姬蜂Agrypon flexorius Thunberg是草地螟Loxostege sticticalis L.老龄幼虫的优势寄生蜂,国内外对其研究报道较少。通过田间调查和室内试验,结果表明:雌雄蜂形态相似,雌蜂个体比雄峰略大。23℃下,草地螟阿格姬蜂经卵、幼虫、蛹发育到成虫,一个世代历期为30³7 d。田间寄生率为3.04%,自然平均雌雄性比为3.97∶1。羽化在寄主成虫出现一周后开始,第5天达到高峰。交尾时间一般537 d。田间寄生率为3.04%,自然平均雌雄性比为3.97∶1。羽化在寄主成虫出现一周后开始,第5天达到高峰。交尾时间一般5¹0 min。产卵时间一般为110 min。产卵时间一般为1²min,卵多产在草地螟头、胸部两侧。草地螟阿格姬蜂大多进行两性生殖,少数进行孤雌生殖。在雌蜂不产卵情况下,补充各种营养的成蜂寿命均在16℃时最长;22℃,补充蔗糖,雌蜂寿命平均为17.11 d。在雌蜂产卵情况下,20%蜂蜜水最适合繁殖。草地螟阿格姬蜂在草地螟4龄幼虫的寄生率最高,平均为40.23%。     

Alteration of life span of mice chronically exposed to 2.45 GHz CW microwaves

Female CD 1 mice were exposed from the thirty-fifth day of age for the remainder of their lives to 2.45 GHz, CW-microwave radiation at a power density of 3 or 10 m W/cm² (SAR = 2.0 or 6.8 W/kg). Exposures took place 1 h/day, 5 day/week in an anechoic chamber at an ambient temperature of 22 °C and a relative humidity of 50%. There were 25 animals in each exposure group, and an equal number of controls were concurrently sham exposed. The average life span of animals exposed at 10 mW/cm² was significantly shorter than that of sham-exposed controls (572 days vs. 706 days; P = .049; truncation >20%). In contrast, the average lifespan of the animals exposed at 3 mW/cm² was slightly, but not significantly, longer (738 days) than that of controls (706 days). © 1994 Wiley-Liss, Inc.

1 This article is a US Government work and, as such, is in the public domain in the United States of America.

     

Comparative laboratory experiment withOrius insidiosus andOrius albidipennis (Het.: anthocoridae), two candidates for biological control in glasshouses

The predatory bugsOrius insidiosus andOrius albidipennis are potential candidates for biocontrol of the thrips,Frankliniella occidentalis. Laboratory experiments showed thatO. albidipennis lays significantly more eggs thanO. insidiosus while its life cycle is shorter. As more eggs are laid byO. albidipennis in the beginning of the oviposition cycle, this anthocorid may be considered as the better biocontrol agent.     

Effects of the Ionic Composition and Water Potential of Aqueous Solution on the Activity and Survival of Orrina phyllobia

The activity and survival of Orrina phyllobia fourth-stage juveniles (J4) were examined in aqueous solutions representing 96 combinations of eight predominant soil solution ions at total concentrations of 100, 200, and 1,000 meq/liter. Various water potentials were imposed by the addition of mannitol or polyethylene glycol to ionic solutions. Nematode longevity increased as water potential was decreased. Longevity was approximately doubled at a water potential of -23 × 10⁵ Pa and more than tripled at -60 × 10⁵ Pa. No combination oflons at 200 meq/liter was lethal after a 6-day exposure. Several ion combinations significantly increased longevity at -10 and -23 × 10⁵ Pa. Single cation Na⁺ solutions consistently inhibited activity and more than doubled nematode longevity.