Independent and Additive Effects of Glutamic Acid and Methionine on Yeast Longevity

Abstract

It is established that glucose restriction extends yeast chronological and replicative lifespan, but little is known about the influence of amino acids on yeast lifespan, although some amino acids were reported to delay aging in rodents. Here we show that amino acid composition greatly alters yeast chronological lifespan. We found that non-essential amino acids (to yeast) methionine and glutamic acid had the most significant impact on yeast chronological lifespan extension, restriction of methionine and/or increase of glutamic acid led to longevity that was not the result of low acetic acid production and acidification in aging media. Remarkably, low methionine, high glutamic acid and glucose restriction additively and independently extended yeast lifespan, which could not be further extended by buffering the medium (pH 6.0). Our preliminary findings using yeasts with gene deletion demonstrate that glutamic acid addition, methionine and glucose restriction prompt yeast longevity through distinct mechanisms. This study may help to fill a gap in yeast model for the fast developing view that nutrient balance is a critical factor to extend lifespan.

StimulatingS-adenosyl-l-methionine synthesis extends lifespan via activation of AMPK

“…All organisms produce ATP by glycolysis through the degradation of glucose. Met or glucose restriction was reported to cause lifespan extension in many eukaryotes (4)(5)(6)(7)(8)(9). Thus, we assumed that consumption of Met and glucose for AdoMet synthesis was required for extended CLS in SSG1-1 and that the CLS of SSG1-1 would be diminished by limiting either the Met or glucose concentration in the medium.…”

“…DR, such as calorie restriction (CR) or Met restriction, extends the lifespan of a wide range of species (4)(5)(6)(7)(8)(9). Although we have knowledge of several metabolites that contribute to the beneficial effects of DR (10)(11)(12), the molecular mechanism underlying the key metabolites responsible for DR regimens is far from complete.…”

Parsing the life-shortening effects of dietary protein: effects of individual amino acids

“…Thus, we further explored the individual role of each amino acid on the high-protein toxicity and we found that the over-representation of methionine (Met), serine (Ser), threonine (Thr) and phenylalanine (Phe) were especially harmful. These amino acids when in excess decrease growth and/or lifespan in a wide variety of life forms such as unicellular algae (Met, Thr and Ser [45]), yeasts (Met, Thr and Ser [46][47][48]), roundworms (Phe [49]), flies (Met [50,51]), rodents (Met, Thr, Ser and Phe [46,[52][53][54]), and even cancer tumour cells (Met and Phe [55]) and other human cells (Met [46]). Methionine is proposed to be related to oxidative stress processes [56].…”

Genetics and Pharmacology of Longevity

“…We already know that, certains amino acids regulate life span with greater effects Piper et al, 2014). Methionine restriction extends the life span of yeast (Johnson & Johnson, 2014;Ruckenstuhl et al, 2014;Wu, Song, Liu, & Huang, 2013), flies , mice (Miller et al, 2005), and rats (Orentreich, (Bass, Grandison, et al, 2007;Mair & Dillin, 2008;Metaxakis & Partridge, 2013)). …”