Abstract
BackgroundDietary restriction (DR) extends lifespan and induces beneficial metabolic effects in many animals. What is far less clear is whether animals retain a metabolic memory to previous DR exposure, that is, can early-life DR preserve beneficial metabolic effects later in life even after the resumption of ad libitum (AL) feeding. We examined a range of metabolic parameters (body mass, body composition (lean and fat mass), glucose tolerance, fed blood glucose, fasting plasma insulin and insulin-like growth factor 1 (IGF-1), insulin sensitivity) in male C57BL/6 mice dietary switched from DR to AL (DR-AL) at 11 months of age (mid life). The converse switch (AL-DR) was also undertaken at this time. We then compared metabolic parameters of the switched mice to one another and to age-matched mice maintained exclusively on an AL or DR diet from early life (3 months of age) at 1 month, 6 months or 10 months post switch.ResultsMale mice dietary switched from AL-DR in mid life adopted the metabolic phenotype of mice exposed to DR from early life, so by the 10-month timepoint the AL-DR mice overlapped significantly with the DR mice in terms of their metabolic phenotype. Those animals switched from DR-AL in mid life showed clear evidence of a glycemic memory, with significantly improved glucose tolerance relative to mice maintained exclusively on AL feeding from early life. This difference in glucose tolerance was still apparent 10 months after the dietary switch, despite body mass, fasting insulin levels and insulin sensitivity all being similar to AL mice at this time.ConclusionsMale C57BL/6 mice retain a long-term glycemic memory of early-life DR, in that glucose tolerance is enhanced in mice switched from DR-AL in mid life, relative to AL mice, even 10 months following the dietary switch. These data therefore indicate that the phenotypic benefits of DR are not completely dissipated following a return to AL feeding. The challenge now is to understand the molecular mechanisms underlying these effects, the time course of these effects and whether similar interventions can confer comparable benefits in humans.
Highlights
Dietary restriction (DR) extends lifespan and induces beneficial metabolic effects in many animals
In the present study we examined whether a mid-life dietary switch from ad libitum (AL) to DR (AL-DR) or from DR to AL (DR-AL) at 11 months of age (8 months of AL feeding or 30% DR respectively) had any impact on a range of metabolic parameters in male C57BL/6 mice
By 1 month after the switch, both the DR-AL and AL-DR groups were significantly lighter than the AL mice, both switch groups were significantly heavier than the DR mice
Summary
Dietary restriction (DR) extends lifespan and induces beneficial metabolic effects in many animals. Dietary switch experiments (from AL to DR or from DR to AL) in mice indicate that the beneficial effects of DR on certain markers of oxidative stress can be improved (or reversed, respectively) within weeks following the switch [23,24]. At least, this reversal in mortality risk through dietary switching can occur at any age [26] It is currently unclear in mice whether a shift from DR to control feeding shifts the rate of ageing this has been demonstrated clearly to be the case in rats [27]
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