Abstract
Studies in young mammals on the molecular effects of food restriction leading to prolong adult life are scares. Here, we used high-throughput quantitative proteomic analysis of whole rat livers to address the molecular basis for growth arrest and the apparent life-prolonging phenotype of the food restriction regimen. Over 1800 common proteins were significantly quantified in livers of ad libitum, restriction- and re-fed rats, which summed up into 92% of the total protein mass of the cells. Compared to restriction, ad libitum cells contained significantly less mitochondrial catabolic enzymes and more cytosolic and ER HSP90 and HSP70 chaperones, which are hallmarks of heat- and chemically-stressed tissues. Following re-feeding, levels of HSPs nearly reached ad libitum levels. The quantitative and qualitative protein values indicated that the restriction regimen was a least stressful condition that used minimal amounts of HSP-chaperones to maintain optimal protein homeostasis and sustain optimal life span. In contrast, the elevated levels of HSP-chaperones in ad libitum tissues were characteristic of a chronic stress, which in the long term could lead to early aging and shorter life span.
Highlights
Children malnutrition, marked by various nutrient deficiencies, is considered a leading cause for growth attenuation and failure to thrive
We have shown previously and in this study that after ten days of 40 % food restriction (RES), the body weight of the young rats merely increased 1.14 fold, whereas in unrestrictedly fed rats (AL), it increased by over 2.2 fold
Confirming that the rapid CU effect on weight was not due solely to the food load in the gut, this trend was observed in individual organs, which were more than twice heavier for ad libitum (AL) than for RES rats
Summary
Children malnutrition, marked by various nutrient deficiencies, is considered a leading cause for growth attenuation and failure to thrive. In young mammals exposed to a period of RES, re-feeding usually leads to catch-up (CU) growth This phenomenon, defined as “height velocity above the normal statistical limits for age and/or maturity during a defined period of time, following a transient period of www.aging‐us.com growth inhibition” [8], is common in children during longitudinal growth, after the removal of a growth inhibiting condition. A continuous mild RES regimen in young adult animals and humans, in which linear growth is minimally affected, is associated with the attenuation of a large spectrum of age-associated diseases, such as diabetes and immune dysfunction [13], leading to an apparent increase of life span [6, 7]
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