Longevity by RNA polymerase III inhibition downstream of TORC1

Three distinct RNA polymerases (Pols) transcribe different classes of genes in the eukaryotic nucleus1. Pol III is the essential, evolutionarily conserved enzyme that generates short, non-coding RNAs, including transfer RNAs (tRNAs) and 5S ribosomal RNA (rRNA)2. Historical focus on transcription of protein-coding genes has left the roles of Pol III in organismal physiology relatively unexplored. The prominent regulator of Pol III activity, Target of Rapamycin kinase Complex 1 (TORC1), is an important longevity determinant3, raising the question of Pol III’s involvement in ageing. Here we show that Pol III limits lifespan downstream of TORC1. We find that a reduction in Pol III extends chronological lifespan in yeast and organismal lifespan in worms and flies. Inhibiting Pol III activity in the adult worm or fly gut is sufficient to extend lifespan, and in flies, longevity can be achieved by Pol III inhibition specifically in the intestinal stem cells (ISCs). The longevity phenotype is associated with amelioration of age-related gut pathology and functional decline, dampened protein synthesis and increased tolerance of proteostatic stress. Importantly, Pol III acts downstream of TORC1 for lifespan and limiting Pol III activity in the adult gut achieves the full longevity benefit of systemic TORC1 inhibition. Hence, Pol III is a pivotal output of this key nutrient signalling network for longevity; Pol III’s growth-promoting, anabolic activity mediates the acceleration of ageing by TORC1. The evolutionary conservation of Pol III affirms its potential as a therapeutic target

International Diversification and Retirement Withdrawals International Diversification and Retirement Withdrawals International Diversification and Retirement Withdrawals

Abstract This study evaluates the success of the monthly withdrawal of funds from hypothetical retirement portfolios for the period January 1930 to December 2001. The objective of this research is to provide an empirical examination of the historical effect of global diversification on the withdrawal of funds from a retirement portfolio. We compare portfolios consisting of U.S. stocks and U.S. corporate bonds, and portfolios consisting of global stocks and U.S. corporate bonds. We examine both portfolio compositions using a variety of portfolio weights, fund withdrawal rates, and fund withdrawal periods. The results of the study indicate that, in general, portfolios with a higher equity portion had a greater likelihood of sustaining a given number of withdrawals over this time. Additionally, for much of the 1930 to 2001 period, including international stocks in a withdrawal portfolio decreased the likelihood the withdrawals lasted for a given period. However, the inclusion of international stocks does increase the terminal value of retirement portfolios after withdrawals during the latter part of the period under study. The results of this study can be used for retirement planning since it provides a historical perspective on the success of various withdrawal rates. The results can also be used to determine the value of the portfolio an individual needs at retirement to fund a given level of withdrawals. This can assist in the retirement timing decision

Partial Inhibition of RNA Polymerase I Promotes Animal Health and Longevity

Health and survival in old age can be improved by changes in gene expression. RNA polymerase (Pol) I is the essential, conserved enzyme whose task is to generate the pre-ribosomal RNA (rRNA). We find that reducing the levels of Pol I activity is sufficient to extend lifespan in the fruit fly. This effect can be recapitulated by partial, adult-restricted inhibition, with both enterocytes and stem cells of the adult midgut emerging as important cell types. In stem cells, Pol I appears to act in the same longevity pathway as Pol III, implicating rRNA synthesis in these cells as the key lifespan determinant. Importantly, reduction in Pol I activity delays broad, agerelated impairment and pathology, improving the function of diverse organ systems. Hence, our study shows that Pol I activity in the adult drives systemic, age-related decline in animal health and anticipates mortality