BackgroundFeatures of life history are subject to environmental regulation in the service of reproductive fitness goals. We have previously shown that the infant-to-childhood transition reflects the adaptive adjustment of an individual's size to the prevailing and anticipated environment.MethodsTo evaluate effects of weaning age on life-history traits in rats, we repeatedly measured length and body mass index (BMI), as well as physiological development and sexual maturation in pups weaned early (d16), normally (d21) or late (d26). Males were bred to females of the same weaning age group for four generations.ResultsHere, we show that the age at weaning from lactation regulates a rat's life history, growth, body composition and maturational tempo. We show that early-weaned rats developed faster than normal- or late-weaned rats; they are leaner and longer than late-weaned ones who are heavier and shorter. Early-weaned progeny develop more rapidly (that is, fur budding, pinnae detachment, eye opening); females show earlier vaginal opening and estrous and males show earlier onset of testicular growth. In generations 3 and 4, early-weaned rats bear larger litter sizes and heavier newborn pups. The entire traits complex is transmitted to subsequent generations from the paternal side.ConclusionsThe findings presented here lend support to the proposition that the duration of infancy, as indexed by weaning age, predicts and perhaps programs growth, body composition, and the tempo of physiological development and maturation, as well as litter size and parity and, thereby, reproductive strategy.

Increased CYP27B1 expression and local duodenal 1,25(OH)2D3 production during puberty may be a metabolic adaptation that promotes dietary calcium absorption. IGF1, a major factor in skeletal growth, is also involved in the modulation of CYP27B1 expression in the gut and may increase calcium supply for the growing bone.

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One hundred years after the discovery of acetylcholine (ACh) by Otto Lowei, ACh receptors, transporters and synthesizing and degrading enzymes became well-recognized contributors to cognition, neuromuscular, metabolic and immune processes. However, newer technologies identified unexpected molecular controllers over ACh signaling, including the SLEEPLESS, Isl1 and Lynx1 genes. These regulators are responsible, among other effects to the fine-tuned identity, functioning modes, dynamics and inter-cellular interactions of cholinergic cell types in and out of the brain, changing our understanding of ACh’s roles in human health and wellbeing. Furthermore, Genome-Wide Association Studies identify new disease-associated mutations and single nucleotide polymorphisms in coding and non-coding sequences within these genes. These discoveries add autism, amyotrophic lateral sclerosis, acute cardiac events, narcolepsy and obesity to the established acquired and inherited neuromuscular, stress-induced, dementia and epilepsy disorders that were traditionally associated with impaired ACh functioning. At the molecular level, cholinergic signaling involves both up- and down-regulation events of transcription, epigenetic modulations, alternative splicing and microRNA suppression that together coordinate the multi-targeted ACh signaling in brain and body functions and are also responsible to the reactions of patients to anti-cholinesterase therapeutics of Alzheimer’s disease as well as to global exposure to agricultural pesticides and to individual tendencies for nicotine addiction, calling for new basic and translational research venues for regulating ACh signaling. Integrating these molecular ACh regulators into every discussion of cholinergic issues, should incorporate data obtained by clinicians and molecular geneticists, neuroscientists and structural biochemists over the past decades into a refreshed look at the intricate checks and balances over cholinergic signaling. Our understanding of the cholinergic regulators is incomplete, but time is ripe to summarize the recent reports on checks and balances of cholinergic signaling and their implications in health and disease.