Browsing by Subject "longevity"

Now showing 1 - 4 of 4
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    Demographic characteristics of Sardinian centenarian genealogies: Preliminary results of the AKeA2 study
    (Demographic Research, 2015-05) Lipsi, Rosa Maria; Caselli, Graziella; Pozzi, Lucia; Baggio, Giovannella; Carru, Ciriaco; Franceschi, Claudio; Vaupel, James W; Deiana, Luca
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    Molecular characterization of numr-1 and numr-2: genes that increase both resistance to metal-induced stress and lifespan in Caenorhabditis elegans
    (2010) Tvermoes, Brooke E; Boyd, Windy A; Freedman, Jonathan H
    To define the mechanisms involved in the molecular response to the carcinogenic metal cadmium, two novel metal-inducible genes from C. elegans were characterized: numr-1 and numr-2 (nuclear localized metal responsive). numr-1 and numr-2 sequences and cellular patterns of expression are identical, indicating that these are functionally equivalent genes. Constitutive transcription of numr-1 and numr-2 is developmentally regulated and occurs in the intestine, in head and tail neurons, and vulva muscles. Exposure to metals induces numr-1 and numr-2 transcription in pharyngeal and intestinal cells. Other environmental stressors do not affect transcription, indicating that these are metal-specific, stress-responsive genes. NUMR-1 and NUMR-2 target to nuclei and colocalize with HSF-1, suggesting that they may be components of nuclear stress granules. Nematodes overexpressing NUMR-1 and NUMR-2 are resistant to stress and live longer than control animals; likewise reducing expression increases sensitivity to metals and decreases neuromuscular functions. Upstream regulatory regions of both genes contain potential binding sites for DAF-16 and SKN-1, which are components of the insulin-IGF-like signaling pathway. This pathway regulates longevity and stress responses in C. elegans. NUMR-1 and NUMR-2 may function to promote resistance to environmental stressors and longevity, which is mediated by the insulin-IGF-like signaling pathway.
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    Telomeres and the natural lifespan limit in humans.
    (Aging (Albany NY), 2017-04) Steenstrup, Troels; Kark, Jeremy D; Verhulst, Simon; Thinggaard, Mikael; Hjelmborg, Jacob VB; Dalgård, Christine; Kyvik, Kirsten Ohm; Christiansen, Lene; Mangino, Massimo; Spector, Timothy D; Petersen, Inge; Kimura, Masayuki; Benetos, Athanase; Labat, Carlos; Sinnreich, Ronit; Hwang, Shih-Jen; Levy, Daniel; Hunt, Steven C; Fitzpatrick, Annette L; Chen, Wei; Berenson, Gerald S; Barbieri, Michelangela; Paolisso, Giuseppe; Gadalla, Shahinaz M; Savage, Sharon A; Christensen, Kaare; Yashin, Anatoliy I; Arbeev, Konstantin G; Aviv, Abraham
    An ongoing debate in demography has focused on whether the human lifespan has a maximal natural limit. Taking a mechanistic perspective, and knowing that short telomeres are associated with diminished longevity, we examined whether telomere length dynamics during adult life could set a maximal natural lifespan limit. We define leukocyte telomere length of 5 kb as the 'telomeric brink', which denotes a high risk of imminent death. We show that a subset of adults may reach the telomeric brink within the current life expectancy and more so for a 100-year life expectancy. Thus, secular trends in life expectancy should confront a biological limit due to crossing the telomeric brink.
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    The co-occurrence of mtDNA mutations on different oxidative phosphorylation subunits, not detected by haplogroup analysis, affects human longevity and is population specific.
    (Aging Cell, 2014-06) Raule, Nicola; Sevini, Federica; Li, Shengting; Barbieri, Annalaura; Tallaro, Federica; Lomartire, Laura; Vianello, Dario; Montesanto, Alberto; Moilanen, Jukka S; Bezrukov, Vladyslav; Blanché, Hélène; Hervonen, Antti; Christensen, Kaare; Deiana, Luca; Gonos, Efstathios S; Kirkwood, Tom BL; Kristensen, Peter; Kristensen, Peter; Leon, Alberta; Pelicci, Pier Giuseppe; Poulain, Michel; Rea, Irene M; Remacle, Josè; Robine, Jean Marie; Schreiber, Stefan; Sikora, Ewa; Eline Slagboom, Peternella; Spazzafumo, Liana; Antonietta Stazi, Maria; Toussaint, Olivier; Vaupel, James W; Rose, Giuseppina; Majamaa, Kari; Perola, Markus; Johnson, Thomas E; Bolund, Lars; Yang, Huanming; Passarino, Giuseppe; Franceschi, Claudio
    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.