Lifespan Extension Via Dietary Restriction: Time to Reconsider the Evolutionary Mechanisms?

Abstract

Dietary restriction (DR) is the most consistent environmental manipulation to extend lifespan. Originally thought to be caused by a reduction in caloric intake, recent evidence suggests that macronutrient intake underpins the effect of DR. The prevailing evolutionary explanations for the DR response are conceptualized under the caloric restriction paradigm, necessitating reconsideration of how or whether these evolutionary explanations fit this macronutrient perspective. In the authors’ opinion, none of the current evolutionary explanations of DR adequately explain the intricacies of observed results; instead a context‐dependent combination of these theories is suggested which is likely to reflect reality. In reviewing the field, it is proposed that the ability to track the destination of different macronutrients within the body will be key to establishing the relative roles of the competing theories. Understanding the evolution of the DR response and its ecological relevance is critical to understanding variation in DR responses and their relevance outside laboratory environments.

A dietary sterol trade off determines lifespan responses to dietary restriction inDrosophila melanogaster

“…There have been several theoretical attempts to describe the mechanistic basis for the lifespan benefits of dietary restriction (Blagosklonny, 2006(Blagosklonny, , 2010Kirkwood & Rose, 1991;Moatt et al, 2020;Regan et al, 2020;Speakman, 2020). In particular, the disposable soma theory proposes that organisms will strategically reallocate nutrients towards somatic maintenance at the cost of reproduction when nutrients are scarce and that this enhances lifespan (Kirkwood & Rose, 1991).…”

“…These data indicate that lifespan and reproduction are not in competition for limiting energy derived from the diet, but instead are optimised at different dietary protein : carbohydrate ratios. In response to these findings, an enormous effort is now focused on uncovering how macronutrient rebalancing, in particular protein dilution, acts to improve lifespan (Blagosklonny, 2006(Blagosklonny, , 2010Moatt et al, 2020;Regan et al, 2020;Speakman, 2020). Accumulating evidence indicates that the effect is mediated by reducing signalling through the amino acid sensitive Target Of Rapamycin (TOR) pathway to enhance cellular proteostasis (Sanz et al, 2004;Ayala et al, 2007;Taylor & Dillin, 2011;Fansonet et al, 2012;Sabatini, 2017).…”

Viral susceptibility across host species is largely independent of dietary protein to carbohydrate ratios

“…Resources are critical in determining immune investment and the level of response to a pathogen challenge in invertebrates (Traniello, Rosengaus, & Savoie, 2002) and development time, longevity, feeding behaviour and reproduction are all affected by dietary modifications (Moatt et al, 2020). In particular protein is fundamental for producing amino acid rich immunological components needed for resistance, particularly to viral pathogens (S.…”

“…Laboratory experiments on dietary restriction, where individuals experienced a reduction in nutrition without inducing malnutrition (differentiated from Calorie Restriction) have been found to extend life span in a range of organisms (Anderson et al, 2003; Klass, 1983; Nakagawa, Lagisz, Hector, & Spencer, 2012; Weindruch & Walford, 1982). The effects of dietary restriction appear to be explained by resource-mediated trade-offs between longevity and reproductive effort (but see review by Moatt et al, 2020). Geometric frameworks - the use of artificial diets with known compositions of specific nutrients that develop an understanding of dimensional nutrient space - have been used to examine the consequences of different ratios of macronutrients across a range of organisms (Fanson, Weldon, Perez-Staples, Simpson, & Taylor, 2009; Jensen, McClure, Priest, & Hunt, 2015; Le Couteur et al, 2016; Lee et al, 2008; Raubenheimer & Simpson, 1999; S.…”

The Hunger Games as the Key to Happily Ever After?

“…25 ). Thus, DR refers to an all-encompassing description for multiple forms of dietary interventions, with CR formally considered as a special case of DR 26 . Nonetheless, the terms DR and CR are used interchangeably by some authors 27 .…”