Paula Juricic's research while affiliated with Max Planck Institute for Biology of Ageing and other places
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Publications (9)
The licensed drug rapamycin has potential to be repurposed for geroprotection. A key challenge is to avoid adverse side effects from continuous dosing. Here we show that geroprotective effects of chronic rapamycin treatment can be obtained with a brief pulse of the drug in early adulthood in female Drosophila and mice. In Drosophila, a brief, early...
The licensed drug rapamycin has potential to be repurposed for geroprotection. A key challenge is to avoid adverse side-effects from continuous dosing regimes. Here we show a profound memory effect of brief, early rapamycin treatment of adults, which extended lifespan in Drosophila to the same degree as lifelong dosing. Lasting memory of earlier ra...
Elevated branched chain amino acids (BCAAs) are associated with obesity and insulin resistance. How long-term dietary BCAAs impact late-life health and lifespan is unknown. Here, we show that when dietary BCAAs are varied against a fixed, isocaloric macronutrient background, long-term exposure to high BCAA diets leads to hyperphagia, obesity and re...
Branched-chain amino acids (BCAAs) have been suggested to be particularly potent activators of TOR signalling. Moreover, increased circulating BCAAs are associated with higher risk of insulin resistance and diabetes in both mice and humans, and with increased mortality in mice. However, it remains unknown if BCAAs play a more prominent role in long...
(Cell Metabolism 25, 610–621; March 7, 2017) In the originally published version of this article, there were errors in the amino acid ratio values reported in the Supplemental Information accompanying the manuscript. They were as follows: in Table S2, (1) the values for columns under FLYAA were a replica of MM3AA, and (2) the “ratio” columns for MM...
Document S1. Supplemental Experimental Procedures, Figures S1?S7, and Tables S1 and S2
Data S1. Templates for Fly Holidic Diets and Calculator for Identifying Limiting AA
See Experimental Procedures. Tab 1: Using the consumer?s average AA proportion and the AA proportions in the diet, this calculator identifies the EAA predicted to be most limiting in the diet. Text in blue is to be modified by the user; all other cells are calculat...
Balancing the quantity and quality of dietary protein relative to other nutrients is a key determinant of evolutionary fitness. A theoretical framework for defining a balanced diet would both reduce the enormous workload to optimize diets empirically and represent a breakthrough toward tailoring diets to the needs of consumers. Here, we report a si...
Citations
... Multiple drugs with anti-aging properties also link nutrient sensing to insulin action with potential ramification on immune function. Rapamycin, an anti-inflammatory drug inhibiting insulin-mTORC1 axis, has long been considered effective in extending lifespan (211), boosting immunity in the elderly (212), and delaying several age-related diseases (213)(214)(215)(216). The mechanism of this immunostimulatory effect of rapamycin are not well characterized, but could be linked to inhibition of mTORC1mediated S6 kinase negative feedback on age-associated chronic insulin signaling (5, 217). ...
... This possibility requires further study, as our analyses were limited and exploratory, and there are well-known concerns about metabolic side effects of 3TC in peripheral tissues (Max & Sherer, 2000;Thet & Siritientong, 2020). Indeed, our data suggest that 3TC may exacerbate the brain aging phenotype for certain metabolites (e.g., lleucine, which is thought to contribute to insulin resistance, a driver of brain aging, and metabolic dysfunction in rodents) (Solon-Biet et al., 2019), so this may be an important area for future work. ...
... These results suggest that lifespan extension is closely linked to TCA cycle and respiratory chain activity. In Drosophila, restriction of the essential amino acids methionine, threonine, histidine, lysine, or BCAAs extends lifespan (Lee et al., 2014;Juricic et al., 2019;Richardson et al., 2021). In rodents, dietary restriction of BCAAs increases mouse health and longevity (Richardson et al., 2021). ...
... 566acids, respectively(Piper et al. 2017). More importantly, while the latter two BCAA form a 567 similar percentages of amino acids in yeast, leucine content in yeast protein is only about 7.5% 568(Piper et al. 2017). ...
... It is, therefore, a principal constraint on evolutionary fitness [1,[4][5][6]. For example, the abundance of protein-rich food has been shown to increase population size or stimulate body growth of birds such as the galah (Eolophus roseicapilus) or the goldfinch (Carduelis carduelis) and mammals like the house mouse (Mus musculus) or several species of squirrels (Sciurus and Tamiasciurus spp.) [7][8][9][10][11][12][13]. In the fruit fly Drosophila melanogaster, we have found that female reproduction is reduced by decreasing overall dietary protein concentration [14][15][16]. We also found that this protein limitation is determined by the concentration of the single most limiting essential Amino Acid (AA) in the diet, which can be identified by comparing the proportion of AAs that is available in food against the proportion of AAs encoded by the fly's exome-a procedure we called exome matching [14][15][16]. ...