Ageing results from complex genetically and epigenetically programmed processes that are elicited in part by noxious or stressful events that cause programmed cell death Here, we report that administration of spermidine, a natural polyamine whose intracellular concentration declines during human ageing, markedly extended the lifespan of yeast, flies and worms, and human immune cells In addition, spermidine administration potently inhibited oxidative stress in ageing mice In ageing yeast, spermidine treatment triggered epigenetic deacetylation of histone H3 through inhibition of histone acetyltransferases (HAT), suppressing oxidative stress and necrosis Conversely, depletion of endogenous polyamines led to hyperacetylation, generation of reactive oxygen species, early necrotic death and decreased lifespan The altered acetylation status of the chromatin led to significant upregulation of various autophagy-related transcripts, triggering autophagy in yeast, flies, worms and human cells Finally, we found that enhanced autophagy is crucial for polyamine-induced suppression of necrosis and enhanced longevity

Induction of autophagy by spermidine promotes longevity

Taurine (a sulfur-containing β-amino acid), creatine (a metabolite of arginine, glycine and methionine), carnosine (a dipeptide; β-alanyl-l-histidine), and 4-hydroxyproline (an imino acid; also often referred to as an amino acid) were discovered in cattle, and the discovery of anserine (a methylated product of carnosine; β-alanyl-1-methyl-l-histidine) also originated with cattle. These five nutrients are highly abundant in beef, and have important physiological roles in anti-oxidative and anti-inflammatory reactions, as well as neurological, muscular, retinal, immunological and cardiovascular function. Of particular note, taurine, carnosine, anserine, and creatine are absent from plants, and hydroxyproline is negligible in many plant-source foods. Consumption of 30 g dry beef can fully meet daily physiological needs of the healthy 70-kg adult human for taurine and carnosine, and can also provide large amounts of creatine, anserine and 4-hydroxyproline to improve human nutrition and health, including metabolic, retinal, immunological, muscular, cartilage, neurological, and cardiovascular health. The present review provides the public with the much-needed knowledge of nutritionally and physiologically significant amino acids, dipeptides and creatine in animal-source foods (including beef). Dietary taurine, creatine, carnosine, anserine and 4-hydroxyproline are beneficial for preventing and treating obesity, cardiovascular dysfunction, and ageing-related disorders, as well as inhibiting tumorigenesis, improving skin and bone health, ameliorating neurological abnormalities, and promoting well being in infants, children and adults. Furthermore, these nutrients may promote the immunological defense of humans against infections by bacteria, fungi, parasites, and viruses (including coronavirus) through enhancing the metabolism and functions of monocytes, macrophages, and other cells of the immune system. Red meat (including beef) is a functional food for optimizing human growth, development and health.

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Important roles of dietary taurine, creatine, carnosine, anserine and 4-hydroxyproline in human nutrition and health.

We analyzed the composition of amino acids (AAs) in oligopeptides, proteins, and the free pool, as well as creatine, agmatine, polyamines, carnosine, anserine, and glutathione, in animal- and plant-derived feedstuffs. Ingredients of animal origins were black soldier fly larvae meal (BSFM), chicken by-product meal, chicken visceral digest, feather meal, Menhaden fishmeal, Peruvian anchovy fishmeal, Southeast Asian fishmeal, spray-dried peptone from enzymes-treated porcine mucosal tissues, poultry by-product meal (pet-food grade), spray-dried poultry plasma, and spray-dried egg product. Ingredients of plant origins were algae spirulina meal, soybean meal, and soy protein concentrate. All animal-derived feedstuffs contained large amounts of all proteinogenic AAs (particularly glycine, proline, glutamate, leucine, lysine, and arginine) and key nonproteinogenic AAs (taurine and 4-hydroxyproline), as well as significant amounts of agmatine, polyamines, creatine, creatinine, creatine phosphate, and glutathione. These nitrogenous substances are essential to either DNA and protein syntheses in cells or energy metabolism in tissues (particularly the brain and skeletal muscle). Of note, chicken by-product meal, poultry by-product meal, and spray-dried poultry plasma contained large amounts of carnosine and anserine (potent antioxidants). Compared with most of the animal-derived feedstuffs, plant-derived feedstuffs contained much lower contents of glycine and proline, little 4-hydroxyproline, and no creatine, creatinine, creatine phosphate, carnosine or anserine. These results indicate the unique importance of animal-source feedstuffs in improving the feed efficiency, growth and health of animals (including fish and companion animals). Because soy protein concentrate is consumed by infants, children and adults, as are BSFM and algae for children and adults, our findings also have important implications for human nutrition.

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Composition of amino acids and related nitrogenous nutrients in feedstuffs for animal diets.

There is wide scale concern about the effects of red meat on human health and climate change. Plant-based meat alternatives, designed to mimic the sensory experience and nutritional value of red meat, have recently been introduced into consumer markets. Plant-based meats are marketed under the premise of environmental and human health benefits and are aimed to appeal a broad consumer base. Meat production is critiqued for its overuse of water supplies, landscape degradation, and greenhouse gas emissions—depending on production practices, environmental footprints may be lower with plant-based meat alternatives. Life-cycle analyses suggests that the novel plant-based meat alternatives have an environmental footprint that may be lower than beef finished in feedlots, but higher than beef raised on well-managed pastures. In this review, we discuss the nutritional and ecological impacts of eating plant-based meat alternatives versus animal meats. Most humans fall on a spectrum of omnivory: they satisfy some nutrient requirements better from plant foods, while needs for other nutrients are met more readily from animal foods. Animal foods also facilitate the uptake of several plant nutrients (zinc and iron), while plant nutrients can offer protection against potentially harmful compounds in cooked meat. Plant and animal foods operate in symbiotic ways to improve human health. The mimicking of animal foods using isolated plant proteins, fats, vitamins, and minerals likely underestimates the true nutritional complexity of whole foods in their natural state, which contain hundreds of nutrients that impact human health. Novel plant-based meat alternatives should arguably be treated as meat alternatives in terms of sensory experience, but perhaps not as true meat replacements in terms of nutrition. If consumers wish to replace some of their meat with plant-based alternatives in the diet (a “flexitarian approach”) this is unlikely to negatively impact their overall nutrient status, but this also depends on what other foods are in their diet and the life stage of the individual.

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Plant-Based Meats, Human Health, and Climate Change

Glutamate (Glu) and glutamine (Gln) comprise a large proportion of total amino acids (AAs) in fish in the free and protein-bound forms. Both Glu and Gln are synthesized de novo from other α-amino acids and ammonia. Although these two AAs had long been considered as nutritionally non-essential AAs for an aquatic animal, they must be included adequately in its diet to support optimal health (particularly intestinal health) and maximal growth. In research on fish nutrition, Glu has been used frequently as an isonitrogenous control on the basis of the assumption that this AA has no nutritional or physiological function. In addition, purified diets used for feeding fish generally lack glutamine. As functional AAs, Glu and Gln are major metabolic fuels for tissues of fish (including the intestine, liver, kidneys, and skeletal muscle), and play important roles not only in protein synthesis but also in glutathione synthesis and anti-oxidative reactions. The universality of Glu and Gln as abundant intracellular AAs depends on their enormous versatility in metabolism. Dietary supplementation with Glu and Gln to farmed fish can improve their growth performance, intestinal development, innate and adaptive immune responses, skeletal muscle development and fillet quality, ammonia removal, and the endocrine status. Glu (mainly as monosodium glutamate), glutamine, or AminoGut (a mixture of Glu and Gln) is a promising feed additive to reduce the use of fishmeal, while gaining the profitability of global aquaculture production. Thus, the concept of dietary requirements of fish for Glu and Gln is a paradigm shift in the nutrition of aquatic animals (including fish).

Nutrition and metabolism of glutamate and glutamine in fish

Dietary polyamines and amino acids (AAs) are crucial for human growth, development, reproduction, and health. However, the scientific literature shows large variations in polyamine and AA concentrations among major staple foods of plant origin, and there is a scarcity of information regarding their complete composition of AAs. To provide a much-needed database, we quantified polyamines, agmatine, and AAs in select plant-source foods. On the dry matter basis, total polyamines were most abundant in corn grains, followed by soybeans, sweet potatoes, pistachio nuts, potatoes, peanuts, wheat flour and white rice in descending order. Glutamine was the most abundant AA in pistachio nuts, wheat flour and white rice, arginine in peanuts, leucine in corn grains, glutamate in soybeans, and asparagine in potatoes and sweet potatoes. Glutamine was the second most abundant AA in corn grains, peanuts, potatoes, and soybeans, arginine in pistachio nuts, proline in wheat flour, and glutamate in sweet potatoes and white rice. Free AAs represented ≤ 3.1% of total AAs in corn grains, peanuts, pistachio nuts, soybeans, wheat flour and white rice, but 34.4% and 28.5% in potatoes and sweet potatoes, respectively. Asparagine accounted for 32.3%, 17.5%, and 19.4% of total free AAs in potatoes, sweet potatoes, and white rice, respectively. The content of histidine, glycine, lysine, tryptophan, methionine, cysteine, and threonine was relatively low in corn grains, potatoes, sweet potatoes, and white rice. All of the analyzed plant-source foods lacked taurine, creatine, carnosine and anserine (antioxidants that are abundant in meats and also present in milk), and contained little 4-hydroxyproline. Proper proportions of plant- and animal-source products are likely most desirable for optimizing human nutrition and health.

Composition of polyamines and amino acids in plant-source foods for human consumption.

The liver plays a central role in amino acid (AA) metabolism in humans and other animals. In all mammals, this organ synthesizes many AAs (including glutamate, glutamine, alanine, aspartate, asparagine, glycine, serine, and homoarginine), glucose, and glutathione (a major antioxidant). Similar biochemical reactions occur in the liver of birds except for those for arginine and glutamine hydrolysis, proline oxidation, and gluconeogenesis from AAs. In contrast to mammals and birds, the liver of fish has high rates of glutamate and glutamine oxidation for ATP production. In most animals (except for cats and possibly some of the other carnivores), the liver produces taurine from methionine or cysteine. However, the activity of this pathway is limited in human infants (particularly preterm infants) and is also low in adult humans as compared with rats, birds and livestock species (e.g., pigs, cattle and sheep). The liver exhibits metabolic zonation and intracellular compartmentation for ureagenesis, uric acid synthesis, and gluconeogenesis, as well as AA degradation and syntheses. Capitalizing on these extensive bases of knowledge, dietary supplementation with functional AAs (e.g., methionine, N-acetylcysteine, and glycine) to humans and other animals can alleviate or prevent oxidative stress and damage in the liver. Because liver diseases are common problems in humans and farm animals (including fish), much research is warranted to further both basic and applied research on hepatic AA metabolism and functions.

Amino Acid Metabolism in the Liver: Nutritional and Physiological Significance.

Both poultry meat and eggs provide high-quality animal protein [containing sufficient amounts and proper ratios of amino acids (AAs)] for human consumption and, therefore, play an important role in the growth, development, and health of all individuals. Because there are growing concerns about the suboptimal efficiencies of poultry production and its impact on environmental sustainability, much attention has been paid to the formulation of low-protein diets and precision nutrition through the addition of low-cost crystalline AAs or alternative sources of animal-protein feedstuffs. This necessitates a better understanding of AA nutrition and metabolism in chickens. Although historic nutrition research has focused on nutritionally essential amino acids (EAAs) that are not synthesized or are inadequately synthesized in the body, increasing evidence shows that the traditionally classified nutritionally nonessential amino acids (NEAAs), such as glutamine and glutamate, have physiological and regulatory roles other than protein synthesis in chicken growth and egg production. In addition, like other avian species, chickens do not synthesize adequately glycine or proline (the most abundant AAs in the body but present in plant-source feedstuffs at low content) relative to their nutritional and physiological needs. Therefore, these two AAs must be sufficient in poultry diets. Animal proteins (including ruminant meat & bone meal and hydrolyzed feather meal) are abundant sources of both glycine and proline in chicken nutrition. Clearly, chickens (including broilers and laying hens) have dietary requirements for all proteinogenic AAs to achieve their maximum productivity and maintain optimum health particularly under adverse conditions such as heat stress and disease. This is a paradigm shift in poultry nutrition from the 70-year-old "ideal protein" concept that concerned only about EAAs to the focus of functional AAs that include both EAAs and NEAAs.

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Amino Acid Nutrition and Metabolism in Chickens.

Amino acids (AAs) and their metabolites play an important role in neurological health and function. They are not only the building blocks of protein but are also neurotransmitters. In the brain, glutamate and aspartate are the major excitatory neurotransmitters, whereas γ-aminobutyrate (GABA, a metabolite of glutamate) and glycine are the major inhibitory neurotransmitters. Nitric oxide (NO, a metabolite of arginine), H2S (a metabolite of cysteine), serotonin (a metabolite of tryptophan) and histamine (a metabolite of histidine), as well as dopamine and norepinephrine (metabolites of tyrosine) are neurotransmitters to modulate synaptic plasticity, neuronal activity, learning, motor control, motivational behavior, emotion, and executive function. Concentrations of glutamine (a precursor of glutamate and aspartate), branched-chain AAs (precursors of glutamate, glutamine and aspartate), L-serine (a precursor of glycine and D-serine), methionine and phenylalanine in plasma are capable of affecting neurotransmission through the syntheses of glutamate, aspartate, and glycine, as well as the competitive transport of tryptophan and tyrosine across from the blood-brain barrier. Adequate consumption of AAs is crucial to maintain their concentrations and the production of neurotransmitters in the central nervous system. Thus, the content and balance of AAs in diets have a profound impact on food intake by animals. Knowledge of AA transport and metabolism in the brain is beneficial for improving the health and well-being of humans and animals.

Metabolism of Amino Acids in the Brain and Their Roles in Regulating Food Intake.

Amino acids are the building blocks of proteins in animals, including swine. With the development of new analytical methods and biochemical research, there is a growing interest in fundamental and applied studies to reexamine the roles and usage of amino acids (AAs) in swine production. In animal nutrition, AAs have been traditionally classified as nutritionally essential (EAAs) or nutritionally nonessential (NEAAs). AAs that are not synthesized de novo must be provided in diets. However, NEAAs synthesized by cells of animals are more abundant than EAAs in the body, but are not synthesized de novo in sufficient amounts for the maximal productivity or optimal health (including resistance to infectious diseases) of swine. This underscores the conceptual limitations of NEAAs in swine protein nutrition. Notably, the National Research Council (NRC 2012) has recognized both arginine and glutamine as conditionally essential AAs for pigs to improve their growth, development, reproduction, and lactation. Results of recent work have also provided compelling evidence for the nutritional essentiality of glutamate, glycine, and proline for young pigs. The inclusion of so-called NEAAs in diets can help balance AAs in diets, reduce the dietary levels of EAAs, and protect the small intestine from oxidative stress, while enhancing the growth performance, feed efficiency, and health of pigs. Thus, both EAAs and NEAAs are needed in diets to meet the requirements of pigs. This notion represents a new paradigm shift in our understanding of swine protein nutrition and is transforming pork production worldwide.

Wenliang He

Papers

Composition of polyamines and amino acids in plant-source foods for human consumption.

Amino Acid Metabolism in the Liver: Nutritional and Physiological Significance.

Amino Acid Nutrition and Metabolism in Chickens.

Metabolism of Amino Acids in the Brain and Their Roles in Regulating Food Intake.

Amino Acids in Swine Nutrition and Production