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At least 1,315 records · Page 73Linked to original sources
PubMed2000

Poly(ADP-ribosyl)ation, genomic instability, and longevity.

Poly(ADP-ribosyl)ation is a DNA strandbreak-driven posttranslational modification of nuclear proteins that is catalyzed by poly(ADP-ribose) polymerase-1 (PARP-1), with NAD+ serving as substrate. Recently, additional PARP isoforms were described that seem to account for a minor fraction of cellular poly(ADP-ribose) synthesis. We have previously described a correlation between poly(ADP-ribosyl)ation capacity of mononuclear leukocytes of various mammalian species and species-specific life span. Likewise, lymphoblastoid cell lines derived from human centenarians display a higher poly(ADP-ribosyl)ation capacity than do controls. At the functional level, recent data show that PARP-1 is a key regulator of alkylation-induced sister-chromatid exchange, imposing a negative control commensurate with the enzyme activity. PARP-1 activity may therefore be responsible for tuning the rate of genomic instability events that are provoked by the constant attack of endogenous and exogenous genotoxins to a level appropriate for the longevity potential of a given organism or species.

Animals↗
PubMed1994

Longevity of dental restorations in selected patients from different practice environments.

The objective of the study was to evaluate the long-term survivals or longevity of dental restorations placed in selected patients from different practice environments in two countries. The case histories of 46 adult patients with 622 restorations placed in three private practices in Pakistan were followed for a minimum of 10 years, and compared with similar assessments of 50 adult patients with 966 restorations placed in a dental hospital in Australia. Amalgam and composite resin restorations showed similar survivals in both countries, but cast gold restorations had much lower survivals in the Pakistan group of patients. In both countries, restoration survivals were significantly better in females, and when patients attended less frequently for treatment. For the Australian group, changes in dental operators also gave significantly better survivals, and there were significant restoration survival differences present between the three practices in Pakistan.

Adult↗
PubMed2026

The Long Haul: Microtubule Motors as the Essential Supply Line for Neuronal Longevity.

The extreme morphology and polarised architecture of neurons require the highly sophisticated microtubule transport system for both construction and lifelong survival. Genomic evidence from an expanding landscape of human mutations supports the essential role of the microtubule transport machinery. During neurodevelopment, mutations disrupt the proliferation and migration of neuronal precursors, as well as the initial establishment of polarity. In the mature nervous system, the reliance on microtubule transport shifts to the long-term maintenance of axon integrity and synaptic proteostasis. Across the motor proteins responsible for long distance transport in neurons, mutations highlight a specific vulnerability of long axons to transport failure in Hereditary Spastic Paraplegia (HSP), Charcot Marie Tooth disease Type 2 (CMT2), Spinal Muscular Atrophy (SMA), Perry Syndrome, and Amyotrophic Lateral Sclerosis (ALS) amongst others. Due to the role of microtubule motors in development and maintenance, there is frequently a phenotypic spectrum within a single gene of the microtubule transport system. For example, mutations in dynein motors are linked both to malformations of cortical development and specific motor neuron loss in SMA-LED (Spinal Muscular Atrophy with Lower Extremity Predominance). By synthesising genetic evidence, this review illustrates how specific molecular failures, ranging from motor-domain kinetics to cargo binding, can inform our understanding of neuronal homeostasis. Ultimately, we argue that microtubule transport is not merely a cellular utility, but a key determinant of neuronal longevity.

Humans↗
PubMed2026

Natural variation in SL6 determines fatty acid components and seed longevity in rice.

Seed longevity (SL) is vital for ensuring food security worldwide. However, the genetic basis of SL has been scarcely documented. Here, we report the cloning of a major SL locus, qSL6, encoding a fatty acyl-ACP thioesterase type B. SL6 is functionally conserved in regulating palmitic acid synthesis in seeds, conferring higher oxidation durability and SL in various species. Through the VP1-SL6 module, a seed desiccation-derived ABA signal is transmitted via VP1, which directly activates SL6 transcription to alter the fatty acid composition and elevate SL in seeds. The ancestral elite allele SL6HHZ harbors a virus-derived CT-rich motif cis-element in the 5'UTR, which serves as a universal, bidirectional mRNA stabilizer, contributing to the divergence between indica and japonica in terms of SL. Moreover, manipulating SL6 expression via marker-assisted selection or transgenic approaches notably improved SL in rice cultivars and F1 hybrids without affecting major agronomic traits. Our findings provided a promising genetic locus for improving SL in rice.

Oryza↗
PubMed1999

Importance of a 5' stem-loop for longevity of papA mRNA in Escherichia coli.

High-level expression of the major pilus subunit (PapA) of uropathogenic strains of Escherichia coli results in part from the unusually long lifetime of the mRNA that encodes this protein. Here we report that the longevity of papA mRNA derives in large measure from the protection afforded by its 5' untranslated region. This papA RNA segment can prolong the lifetime of an otherwise short-lived mRNA to which it is fused. In vivo alkylation studies indicate that, in its natural milieu, the papA message begins with a stem-loop structure. This stem-loop is important for the stabilizing effect of the papA 5' untranslated region, as evidenced by the significant acceleration in papA mRNA decay that results from its removal.

5' Untranslated Regions↗
PubMed1987

A Podospora anserina longevity mutant with a temperature-sensitive phenotype for senescence.

A Podospora anserina longevity mutant was identified with a temperature-sensitive phenotype for senescence. This mutant, termed TS1, grew for over 3 m at 27 degrees C, but when shifted to 34 degrees C, it underwent senescence between 10 and 18 cm. A previously described senescence-associated plasmid, alpha senDNA, derived from the mitochondrial genome, was not detected in TS1 at 27 degrees C but was present in senescent cultures at 34 degrees C. A similar result was observed in progeny strains obtained by crossing the TS1 mutant with a wild-type strain. Other mitochondrial excision-amplification DNAs in addition to alpha senDNA were also observed in the senescent cultures. Most were derived from a specific region of the mitochondrial genome. These results provide evidence that alpha senDNA is involved in TS1 senescence and suggest that this plasmid may play a role in the formation of other mitochondrial excision-amplification plasmids.

Aging↗
PubMed2002

Impact of codon usage modification on T cell immunogenicity and longevity of HIV-1 gag-specific DNA vaccines.

In this study, we analyzed the in vitro expression, potency and longevity of immune responses induced in a Balb/c mouse model by a synthetic HIV-1 GAG gene exhibiting a codon usage that was adapted to that of highly expressed mammalian genes (syngag). In contrast to a vector containing the wild-type (wt) GAG gene, the syngag construct enabled highly efficient Gag expression in both human and rodent cell lines in complete absence of Rev and Rev-responsive element. Immunization of Balb/c mice with the wt gag plasmid DNA induced only weak and inconsistent humoral immune responses. Mice vaccinated by syngag but not wt gag developed substantial and highly consistent Gag-specific antibody titers showing a clear T helper 1 polarization even with low doses of DNA. Moreover, vaccinated mice developed a strong Gag-specific cellular immune response, including cytotoxic T cells, which was not observed in wt gag-immunized animals. Both humoral and cellular immunity were efficient and lasted for more than 20 weeks. Furthermore, the induction of the humoral as well as the cellular immune response was independent of the immunization route (intramuscular or subcutaneous). These results clearly show the advantages of codon-optimized genes with respect to the expression and immunogenicity of plasmid DNA constructs, making them promising vaccine candidates for further studies.

AIDS Vaccines↗
PubMed1983

Genetic effects on the longevity of cultured human fibroblasts. II. DNA repair deficient syndromes.

The lifespan of fibroblasts from genetic syndromes with reduced DNA repair or chromosome stability has been measured. Cells from Bloom's syndrome, Cockayne's syndrome, Fanconi's anaemia and 2 out of 3 cases of ataxia telangiectasia had a significantly reduced growth potential in comparison to controls. In each case the longevity of several parallel populations was measured and the greatest variability in lifespan was observed with Cockayne's syndrome cells. The fibroblasts from 1 ataxia telangiectasia patient and a Friedreich's ataxia patient grew to the passage levels seen in control cultures. The results suggest that repair processes are necessary for cells to achieve their maximum in vitro lifespan, and support the error theory rather than the programme theory of ageing.

Aged↗
PubMed1983

Genetic effects on the longevity of cultured human fibroblasts. III. Correlations with altered glucose-6-phosphate dehydrogenase.

The level of heat-labile glucose-6-phosphate dehydrogenase (G6PD) has been measured in skin fibroblast cultures from premature ageing or DNA repair deficient genetic syndromes. The short in vitro longevity of Werner's syndrome, progeria, Cockayne's syndrome, ataxia telangiectasia, Fanconi's anaemia, and Bloom's syndrome cultures was correlated with the appearance of a significant fraction of heat-labile enzyme. Long-lived control cultures contain a low level of altered enzyme until they become senescent. The evidence that heat-labile G6PD molecules are derived from errors in synthesis, or from other causes, is critically assessed. It is shown that normal cells grown in medium containing the antibiotic, paromomycin, which is known to reduce the fidelity of ribosomal translation, produce a significant fraction of altered G6PD.

Aged↗
PubMed2003

Blood pressure, risk of ischemic cerebrovascular and ischemic heart disease, and longevity in alpha(1)-antitrypsin deficiency: the Copenhagen City Heart Study.

BACKGROUND: Because elastase in alpha(1)-antitrypsin deficiency may attack elastin in the arterial wall, we tested whether alpha(1)-antitrypsin deficiency is associated with reduced blood pressure, risk of ischemic cerebrovascular (ICVD) and ischemic heart disease (IHD), and longevity. METHODS AND RESULTS: We genotyped 7963 control subjects from the adult general population of Denmark, 1131 Danish patients with ICVD, and 2221 Danish patients with IHD. Compared with MM/MS individuals, systolic blood pressure was lower by 15 mm Hg in ZZ homozygotes (n=6, P=0.03) and 9 mm Hg in MZ heterozygotes with IHD (n=39, P=0.02). Odds ratios for ICVD and IHD in MZ versus MM/MS individuals were 0.70 (0.51 to 0.96) and 0.77 (0.61 to 0.98). Finally, mean ages of MZ and MM/MS control subjects were 58 and 56 years (Mann-Whitney: P=0.008), and relative alpha(1)-antitrypsin MZ genotype frequencies increased from 20 to 93 years among control subjects (chi(2), P=0.002). CONCLUSIONS: ZZ alpha(1)-antitrypsin deficiency and MZ intermediate deficiency in the context of IHD are associated with reduced blood pressure, and MZ is associated with reduced risk of ICVD and IHD. Because MZ heterozygosity was associated with increased age, MZ heterozygosity could be a beneficial condition.

Adult↗
PubMed2000

Factors affecting longevity of homograft valves used in right ventricular outflow tract reconstruction for congenital heart disease.

BACKGROUND: Few studies have explored the long-term function of cryopreserved homograft valves used for reconstruction of the right ventricular tract (RVOT) in patients with congenital heart disease. METHODS AND RESULTS: Among 205 patients receiving cryopreserved homografts for reconstruction of the RVOT between November 1985 and April 1999, the outcome of 220 homografts in 183 operative survivors was analyzed. There were 150 pulmonary and 70 aortic homografts used. Median age at implantation was 4.4 years (mean 6.9+/-7.6 years, range 3 days to 48 years). End points included (1) patient survival, (2) homograft failure (valve explant or late death), and (3) homograft dysfunction (homograft insufficiency or homograft stenosis). Survival was 88% at 10 years. Freedom from homograft failure was 74+/-4% at 5 years and 54+/-7% at 10 years. Univariable analysis identified younger age, longer donor warm ischemic time, valve Z: value <2, and previous procedure as risk factors for homograft failure and dysfunction. Aortic homograft type and extracardiac operative technique predicted homograft failure but not dysfunction. For patients </=1 year of age, valve type did not predict failure or dysfunction. Multivariable analysis identified younger age and longer donor warm ischemic time as risk factors for homograft failure and dysfunction, whereas, Z: value <2 and aortic valve type predicted homograft valve failure. CONCLUSIONS: Homograft valves used for RVOT reconstruction provide effective intermediate palliation with excellent late survival. Factors that adversely affect graft longevity include younger age, longer donor warm ischemic time, smaller homograft size, use of aortic homograft in the older patient, and extracardiac operative technique.

Adolescent↗
PubMed2000

Organizational characteristics and issues affecting the longevity of self-help groups for parents of children with special needs.

In this article, the organizational characteristics and issues affecting the maintenance of nine self-help groups for parents of children with special needs are discussed. Qualitative data were collected through interviews with 20 parents and observation of six group meetings. For continued existence, groups must deal with the challenges of encouraging new leaders, attracting new members, obtaining funds or assistance to support their activities, and meeting the changing needs of members. Important organizational characteristics associated with longevity are committed and effective leadership, community connections that help provide needed funds or practical assistance, and the willingness of group members to change activities to meet changing needs. This information can be used by parents and service providers to plan new groups, recruit group members, and ensure the effective functioning of groups as they change over time.

Adult↗
PubMed2005

Nanoparticles and cell longevity.

The field of engineering has made substantial strides in nanotechnology, in the realm of materials science and construction of nanoscale devices. Nanomedicine encompasses application of cutting edge engineered nanostructures to biological systems and development of novel strategies for disease intervention. In the current review, we discuss the pharmacological application of nanoparticles as free radical scavengers and the capacity of nanoparticles to promote cell and organismal longevity.

Cell Survival↗
PubMed1994

Enhanced interleukin-1 beta release and longevity of glioma-associated peripheral blood monocytes in vitro.

Interleukin-1 (IL-1) plays a controversial role in the immune response. Besides its activation of immune cells and juvenile central nervous system cells, monocyte-derived IL-1 may be able to stimulate the malignant transformation and proliferation of glial brain tumor cells expressing IL-1 receptors. The aim of this study was to determine the growth pattern and the IL-1 beta release of long-term cultured peripheral blood monocytes of glioma patients. At 6- to 7-day intervals, the vital monocytes, characterized by CD14 immunophenotyping, were counted. By the use of a specific IL-1 beta enzyme-linked immunosorbent assay, the IL-1 beta content of monocyte culture supernatants derived from 13 subjects with glioma and from 12 controls were compared at Days 7, 21, and 100 of culture. Cell clusters of monocytes derived from glioblastoma patients survived more than 250 days in culture, whereas control monocytes survived only up to 114 days. The IL-1 beta release of glioma-associated peripheral blood monocyte cultures was about 50 times higher as compared with control monocyte cultures. Dexamethasone treatment at the time of blood sampling and recurrences of the gliomas did not influence the increase in the IL-1 beta expression of glioma monocytes. It seemed that at least subsets of glioma-associated blood monocytes, although they had been removed from the circulation, remained activated for a long period of time. We conclude that increased IL-1 beta production of glioma-associated peripheral blood monocytes and their longevity in vitro may be features of aberrant immune cell subsets. In future studies, the exact phenotyping of monocyte subsets will be mandatory.

Adult↗
PubMed1984

In search of treatment longevity--a 30-year perspective.

Consumers spent $10 billion on restorative dental treatment in 1979. Little information is available regarding the life expectancy of these restorations or what proportion of these restorations replaces previous ones. A critical literature review was presented, covering all available longevity data of posterior restorations. Necessary methodologic standards for evaluation of the studies were outlined and used in the review. The lack of these critical variables--patient selection, missing follow-up data, and judgment criteria for determining need for replacement or failure (or both)--minimized the usefulness of the results. Study results are generalizable only to similar patient populations and not all patients. Much more controlled research needs to be done.

Clinical Competence↗
PubMed1995

Evaluating the longevity of restorative materials that seal the root canals of overdenture abutments.

Researchers have not established which restorative materials are most appropriate to seal the root canals of overdenture abutments. The author evaluated the longevity of a spherical amalgam, a composite resin and a glass ionomer in 123 patients. Results of this study showed a significant difference between the glass ionomer and the other two materials with regard to the time from placement to replacement of the restorations.

Aged↗