The polygenic nature of telomere length and the anti-ageing properties of lithium

Telomere length is a promising biomarker for age-related disease and a potential anti-ageing drug target. Here, we study the genetic architecture of telomere length and the repositioning potential of lithium as an anti-ageing medication. LD score regression applied to the largest telomere length genome-wide association study to-date, revealed SNP-chip heritability estimates of 7.29%, with polygenic risk scoring capturing 4.4% of the variance in telomere length in an independent cohort (p = 6.17 × 10-5). Gene-enrichment analysis identified 13 genes associated with telomere length, with the most significant being the leucine rich repeat gene, LRRC34 (p = 3.69 × 10-18). In the context of lithium, we confirm that chronic use in a sample of 384 bipolar disorder patients is associated with longer telomeres (p = 0.03). As complementary evidence, we studied three orthologs of telomere length regulators in a Caenorhabditis elegans model of lithium-induced extended longevity and found all transcripts to be affected post-treatment (p  0.05). Consequently, this suggests that lithium may be catalysing the activity of endogenous mechanisms that promote telomere lengthening, whereby its efficacy eventually becomes limited by each individual's inherent telomere maintenance capabilities. Our work indicates a potential use of polygenic risk scoring for the prediction of adult telomere length and consequently lithium's anti-ageing efficacy

Josephus In Galilee and Rome : His Vita and development as a history

Leidenxvi, 277 p.; 25 c

University of California Press eScholarship editions in process

In modern times, various Jewish groups have argued whether Jewishness is a function of ethnicity, of nationality, of religion, or of all three. These fundamental conceptions were already in place in antiquity. The peculiar combination of ethnicity, nationality, and religion that would characterize Jewishness through the centuries first took shape in the second century B.C.E. This brilliantly argued, accessible book unravels one of the most complex issues of late antiquity by showing how these elements were understood and applied in the construction of Jewish identity - by Jews, by gentiles, and by the state.Beginning with the intriguing case of Herod the Great's Jewishness, Cohen moves on to discuss what made or did not make Jewish identity during the period, the question of conversion, the prohibition of intermarriage, matrilineal descent, and the place of the convert in the Jewish and non-Jewish worlds. His superb study is unique in that it draws on a wide range of sources: Jewish literature written in Greek, classical sources, and rabbinic texts, both ancient and medieval. It also features a detailed discussion of many of the central rabbinic texts dealing with conversion to Judaism

From the Maccabees to the Mishnah

Philadelphia251 p.; 23 c

From the Maccabees to the Mishnah

Philadelphia251 p.; 23 c