Extended Longevity of Reproductives Appears to be Common in Fukomys Mole-Rats (Rodentia, Bathyergidae)

African mole-rats (Bathyergidae, Rodentia) contain several social, cooperatively breeding species with low extrinsic mortality and unusually high longevity. All social bathyergids live in multigenerational families where reproduction is skewed towards a few breeding individuals. Most of their offspring remain as reproductively inactive “helpers” in their natal families, often for several years. This “reproductive subdivision” of mole-rat societies might be of interest for ageing research, as in at least one social bathyergid (Ansell's mole-rats Fukomys anselli), breeders have been shown to age significantly slower than non-breeders. These animals thus provide excellent conditions for studying the epigenetics of senescence by comparing divergent longevities within the same genotypes without the inescapable short-comings of inter-species comparisons. It has been claimed that many if not all social mole-rat species may have evolved similar ageing patterns, too. However, this remains unclear on account of the scarcity of reliable datasets on the subject. We therefore analyzed a 20-year breeding record of Giant mole-rats Fukomys mechowii, another social bathyergid species. We found that breeders indeed lived significantly longer than helpers (ca. 1.5–2.2fold depending on the sex), irrespective of social rank or other potentially confounding factors. Considering the phylogenetic positions of F. mechowii and F. anselli and unpublished data on a third Fukomys-species (F. damarensis) showing essentially the same pattern, it seems probable that the reversal of the classic trade-off between somatic maintenance and sexual reproduction is characteristic of the whole genus and hence of the vast majority of social mole-rats

Influence of local treatment on the biology of advanced prostate cancer : Treatment of the primary tumor may delay hormone resistance of metastases

Hintergrund: In den letzten 15 Jahren zeigt sich ein Trend hin zu einem längeren Überleben beim metastasierten Prostatakarzinom. Neben dem durch neue Medikamente bedingten Fortschritt deuten retrospektive Daten auch auf einen möglichen positiven Effekt einer früheren Primärtumorbehandlung hin. Fragestellung: Kann eine Primärtumorbehandlung im Falle einer späteren Metastasierung die Prognose der betroffenen Patienten verbessern und wenn ja, über welche Mechanismen? Material und Methode: Wir werteten die klinischen Langzeitergebnisse von 115 Patienten aus, die bei T4-Prostatakarzinomen nach induktiver Hormontherapie an unserer Klinik prostatektomiert worden waren. Weiterhin erfolgte eine kritische Durchsicht und Diskussion der zur oben genannten Fragestellung vorhandenen Literatur. Ergebnisse: Von den 115 Patienten hatten 84 im weiteren Verlauf ein biochemisches Rezidiv erlitten, waren also definitiv durch die radikale Prostatektomie nicht geheilt. Das tumorspezifische und das Gesamtüberleben dieser 84 Patienten lag nach 150 Monaten bei 61 % bzw. 44 %. Bemerkenswert war die Beobachtung, dass diese Patienten ein überraschend gutes und langes Ansprechen auf eine Hormontherapie zeigten. Von den 84 Patienten waren nach durchschnittlich 95 Monaten Nachbeobachtungszeit noch 47 am Leben. 31 von ihnen, also ungefähr zwei Drittel, standen immer noch unter einer Standardhormontherapie. Nur 13 hatten eine Resistenz gegen die primäre Hormontherapie entwickelt und entsprechend eine tertiäre Hormontherapie erhalten, auf die sie teilweise aber auch wieder langfristig sensibel blieben. Schlussfolgerungen:Die Primärtumorentfernung, zumindest unter den beschriebenen Begleitumständen, scheint die Entwicklung einer Hormonresistenz beim metasta sierten Prostatakarzinom hinauszögern und in Einzelfällen sogar ganz verhindern zu können.In metastatic prostate cancer, a trend towards longer survival has been observed over the last 15 years. Beyond progress due to new drugs, retrospective data also suggest a positive influence of a prior treatment of the primary tumor. Objectives: Can treatment of the primary tumor improve the prognosis of patients later developing metastases, and if yes, what are the underlying mechanisms. Materials and methods: In addition to a critical review and discussion of the literature, we analyzed the long-term outcomes of 115 patients with T4 prostate cancer, who had undergone radical prostatectomy after inductive hormonal therapy at our institution. Results: Of the 115 patients, 84 developed prostate-specific antigen (PSA) recurrence during the further course of disease and must therefore be regarded as uncured. Tumor-specific and overall survival of these 84 patients after 150 months were 61 and 44%, respectively. A total of 47 patients were alive after a median follow-up time of 95 months, of whom 31 were still receiving standard hormonal therapy. Only 13 had developed resistance towards their primary hormonal therapy and, hence, received tertiary hormonal therapy. Again, long-term responses were found in some of these patients. Conclusions: Primary tumor resection, at least under the circumstances described here, seems to delay the development of castration resistance in metastatic prostate cancer or to completely prevent it in individual cases

Reproductive effort and survival in breeding females (n = 20).

<p>Univariate Cox analyses: hazard ratio point estimates and 95% confidence intervals (CI) and p-values (2-tailed) from Wald tests are reported. Null hypothesis (no effect): hazard ratio = 1. Ratios <1 indicate positive, >1 negative effects of a given parameter in units of the respective variable on survival. Except age at pairing, all parameters refer to a defined period of time (the first two years after delivery of the first litter) in order to standardize the data.</p>a<p>lactation effort defined as: number of sucklings * their respective lifespan before weaning at approx. 90 days <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0018757#pone.0018757-Scharff1" target="_blank">[10]</a>.</p>#<p>Note that the units of some variables differ between the descriptive (mean ± SD) and the inferential illustration in the cox model. This transformation was necessary to better display the hazard ration point estimates.</p

Survival curves of breeding and non-breeding <i>Fukomys mechowii</i>.

<p>Breeders lived significantly longer than non-breeders (log rank test, df = 1, χ² = 15.49, <i>P</i><0.001). There was no difference between males and females in either reproductive group (breeders ♀♀ vs. ♂♂ df = 1, χ² = 0.21, <i>P</i> = 0.65; non-breeders ♀♀ vs. ♂♂ df = 1, χ² = 0.01, <i>P</i> = 0.92).</p

Phylogeny of the genus <i>Fukomys</i>.

<p>Combined phylogeny based on TTR Intron I, 12sRNA and cyt <i>b</i> sequences; adopted from <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0018757#pone.0018757-DaveySmith1" target="_blank">[27]</a> and <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0018757#pone.0018757-Young1" target="_blank">[28]</a>.</p

Survival of non-breeders growing up in different social environments.

<p>Sexes combined. Survival probabilities did not differ between dominant (early-born) and subdominant (late-born) non-breeders (log rank test, df = 1, χ² = 0.05, <i>P</i> = 0.82).</p