{"id":1043498,"date":"2013-03-17T02:58:56","date_gmt":"2013-03-17T06:58:56","guid":{"rendered":"http:\/\/www.longevitymedicine.tv\/malate-and-nematode-lifespan\/"},"modified":"2024-08-17T17:05:00","modified_gmt":"2024-08-17T21:05:00","slug":"malate-and-nematode-lifespan","status":"publish","type":"post","link":"https:\/\/www.euvolution.com\/futurist-transhuman-news-blog\/longevity-medicine\/malate-and-nematode-lifespan.php","title":{"rendered":"Malate and Nematode Lifespan"},"content":{"rendered":"

The smaller and shorter lived the animal, the easier it is to extend its life in the laboratory. This is in part because more experiments can run at lower cost, but also because it seems that many of the evolved, shared mechanisms for adjusting the pace of aging or degree of tissue maintenance in response to environmental circumstances (e.g. calorie restriction<\/a>) have a larger effect in shorter-lived species.<\/p>\n

Any given mechanism for lengthening life span can be triggered or partially triggered or gently influenced in numerous ways. A lot of present research is focused on enumerating these many methods, and then matching them up to the few known underlying mechanisms for lengthening life. So we see research publications like this one:<\/p>\n

Although mitochondrial-derived oxygen radicals<\/a> have been questioned as the main driving force for the aging process, changes in mitochondrial metabolism<\/a> almost certainly play a role. Dietary restriction (DR), which extends lifespan, also delays the aging-induced electron transport chain<\/a> dysfunction in rodents. DR increases the NAD\/NADH ratio<\/a> in many tissues, which stimulates mitochondrial tricarboxylic acid (TCA) cycle<\/a> dehydrogenases<\/a> that utilize NAD as a cofactor. The increased TCA cycle function likely necessitates increased anaplerosis<\/a>, important for longevity.<\/p>\n

Alteration of mitochondrial TCA cycle function influences lifespan in C. elegans. Malate<\/a>, the tricarboxylic acid (TCA) cycle metabolite, increased lifespan and thermotolerance in the nematode C. elegans<\/a>. The increased longevity provided by malate addition did not occur in fumarase (fum-1)<\/a>, glyoxylate shunt (gei-7)<\/a>, succinate dehydrogenase flavoprotein (sdha-2)<\/a>, or soluble fumarate reductase F48E8.3<\/a> RNAi knockdown worms. Therefore, to increase lifespan, malate must be first converted to fumarate, then fumarate must be reduced to succinate by soluble fumarate reductase and the mitochondrial electron transport chain complex II<\/a>. <\/p>\n

Lifespan extension induced by malate depended upon the longevity regulators DAF-16<\/a> and SIR-2.1<\/a>. Malate supplementation did not extend the lifespan of long-lived eat-2 mutant worms<\/a>, a model of dietary restriction. Malate and fumarate addition increased oxygen consumption, but decreased ATP<\/a> levels and mitochondrial membrane potential<\/a> suggesting a mild uncoupling of oxidative phosphorylation<\/a>. Malate also increased NADPH, NAD, and the NAD\/NADH ratio. Fumarate reduction, glyoxylate shunt activity, and mild mitochondrial uncoupling likely contribute to the lifespan extension induced by malate and fumarate by increasing the amount of oxidized NAD and FAD cofactors.<\/i><\/p><\/blockquote>\n

Link: http:\/\/dx.doi.org\/10.1371\/journal.pone.0058345<\/a><\/span><\/p>\n

Source:
http:\/\/www.fightaging.org\/archives\/2013\/03\/malate-and-nematode-lifespan.php<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"

The smaller and shorter lived the animal, the easier it is to extend its life in the laboratory. This is in part because more experiments can run at lower cost, but also because it seems that many of the evolved, … Continue reading →<\/span><\/a><\/p>\n","protected":false},"author":64,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"limit_modified_date":"","last_modified_date":"","_lmt_disableupdate":"","_lmt_disable":"","footnotes":""},"categories":[1246678],"tags":[],"class_list":["post-1043498","post","type-post","status-publish","format-standard","hentry","category-longevity-medicine"],"modified_by":null,"_links":{"self":[{"href":"https:\/\/www.euvolution.com\/futurist-transhuman-news-blog\/wp-json\/wp\/v2\/posts\/1043498"}],"collection":[{"href":"https:\/\/www.euvolution.com\/futurist-transhuman-news-blog\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.euvolution.com\/futurist-transhuman-news-blog\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.euvolution.com\/futurist-transhuman-news-blog\/wp-json\/wp\/v2\/users\/64"}],"replies":[{"embeddable":true,"href":"https:\/\/www.euvolution.com\/futurist-transhuman-news-blog\/wp-json\/wp\/v2\/comments?post=1043498"}],"version-history":[{"count":0,"href":"https:\/\/www.euvolution.com\/futurist-transhuman-news-blog\/wp-json\/wp\/v2\/posts\/1043498\/revisions"}],"wp:attachment":[{"href":"https:\/\/www.euvolution.com\/futurist-transhuman-news-blog\/wp-json\/wp\/v2\/media?parent=1043498"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.euvolution.com\/futurist-transhuman-news-blog\/wp-json\/wp\/v2\/categories?post=1043498"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.euvolution.com\/futurist-transhuman-news-blog\/wp-json\/wp\/v2\/tags?post=1043498"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}