Dietary restriction and insulin‐like signalling pathways as adaptive plasticity: A synthesis and re‐evaluation

Abstract

Dietary restriction (DR) under laboratory conditions generally extends life spanand delays ageing across species as diverse as yeast, nematode worms, flies and mice, and is underpinned by taxonomically conserved physiological pathways, notably the insulin-like signalling pathway (IIS). Despite growing excitement about the links between DR/IIS and ageing within biogerontology, our understanding of why the DR response and associated pathways evolved under natural selection remains controversial and limited.2. Here, we provide a brief overview of current understanding of the relationship between DR and IIS and ageing from modern biogerontology and go on to summarize the evidence that the IIS pathway integrates a range of important environmental cues including photoperiod, temperature and humidity, as well as nutrition.3. We go on to discuss the main existing evolutionary explanations for DR and argue that they are not mutually exclusive and are too nutrition-focussed to fully explain the evolutionary origin of the IIS pathway. In the wild, environmental cues and pressures are dynamic and multivariate, and physiological pathways capable of integrating multiple predictive cues could be strongly favoured by natural selection.4. We hypothesize that the IIS and related pathways, such as mTOR, evolved to detect and integrate a wide range of environmental cues (not just diet) that are predictive of important selective pressures in the wild. Available evidence suggests the pathway is capable of triggering a range of phenotypic responses, depending on the cues provided, ranging from profound physiological remodelling (e.g. diapause, aestivation, hibernation) associated with promoting survival through challenging environments, to more subtle responses to acute, fine-scale variation in the environment which may allow individuals to better match their level of reproductive investment to their conditions. 5. We argue that the IIS pathway underpins important adaptive phenotypic plastic responses to a wide range of environmental inputs, of which diet is just one. A multi-disciplinary approach combining perspectives and methods from biogerontology, cell biology, ecology and evolutionary biology will be essential to develop our understanding of the evolutionary origins of this pathway and the way natural K E Y W O R D S cues, mechanistic target of rapamycin (mTOR), natural selection, nutrient sensing, phenotypic plasticity, photoperiod, wild animals | 109 Functional Ecology REGAN Et Al.

The hidden costs of dietary restriction: Implications for its evolutionary and mechanistic origins

“…A recent reappreciation of the evolutionary biology of DR (and molecular nutrient-sensing pathways) suggests that phenotypic plasticity is at the core of the evolutionary explanation of DR (19). We find that flies are highly plastic in modulating their reproduction to dietary conditions.…”

“…This "somatic maintenance response" has been presumed to be the primary causative agent in the pro-longevity DR response (1,15,16). There are few alternatives to the somatic maintenance response model that can explain the evolutionary biology of DR [but see (17)(18)(19)], and its elemental phenotypic predictions have undergone minimal empirical examination [but see (20)].…”

Insulin-like growth factor 1 is related to the expression of plumage traits in a passerine species

“…In molting birds, higher individual levels of IGF-1 might stimulate feather development and facilitate the display of more elaborated plumage features. IGF-1 levels were shown to be negatively affected by dietary restrictions (e.g., reduction of the diet and/or protein content) in several vertebrate species, and circulating levels are suggested to play a role in reflecting the nutritional status of cells and regulating energy metabolism (Breier 1999;Regan et al 2019). Furthermore, IGF-1 promotes protein synthesis in tissues, which might play an important role in the development and growth of plumage, in particular considering the high demand for proteins during feather growth (Murphy and King 1992).…”

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

“…Recent experimental work across a broad range of taxa has challenged the disposable soma theory by demonstrating that reproduction and lifespan respond predominantly to the balance of dietary macronutrients, not the overall energy content of the diet (Mair et al, 2005;Lee et al, 2008;Skorupa et al, 2008;Grandison et al, 2009;Solon-Biet et al, 2014;Solon-Biet et al, 2015;Simpson et al, 2017;Regan et al, 2020). Specifically, high protein, low carbohydrate diets are consistently associated with high reproduction and short lifespan, while low protein, high carbohydrate diets are associated with longer lifespan and lower levels of reproduction (Piper et al, 2011;Simpson et al, 2017).…”