Table 2.
Studies of serine improving aspects of age-related diseases in diverse animal models
| Study | Animal models | Intervention | Effect on age-related pathologies | Mechanism |
|---|---|---|---|---|
| Maternal serine supplementation on high-fat diet-induced oxidative stress [99] | C57BL/6 J mouse dams during gestation with HF diet | 1% serine supplementation during pregnancy | Maternal serine prevents oxidative stress and fat accumulation in weanlings from dams fed high-fat diet | Serine alleviates HF diet-induced oxidative stress by epigenetically regulating glutathione synthesis |
| L-serine supplementation in diquat-induced oxidative stress in mice [100] | Mice model of diquat-induced oxidative stress | L-serine was supplemented in the drinking water for 14 days | Serine supplementation improved glutathione synthesis and alleviated oxidative stress | Serine alleviated oxidative stress via supporting glutathione synthesis and methionine cycle |
| Effects of serine on acute pancreatitis during diabetes in mice [16] | Mouse model of diabetes | 10% L-serine supplementation in diabetic mice | L-serine supplementation reduced the acinar tissue damage resulting from pancreatitis in diabetic mice | L-serine decreased the ROS production, ER stress and cellular apoptosis in acinar tissue |
| L‐serine in ALS/Parkinsonism dementia [101] | Rat model of ALS/Parkinsonism dementia complex | L-serine solution was injected intraperitoneally daily for 1 week into the model rats | Administration of L-serine enhanced cognitive function, and ameliorated electrophysiological abnormalities | L‐serine alleviated apoptotic and autophagic changes in the central nerve system |
| L-serine supplementation in autoimmune diabetes [102] | Autoimmune diabetic model in NOD mice | Supplementation of L-serine 85.7 g/L, or 280 mg/day/mouse in water | Supplementation of L-serine reduced diabetes incidence and insulitis score | L-serine protects against autoimmune diabetes by regulating pancreas sphingolipid composition |
| Long-term effects of L-serine supplementation in diabetic neuropathy [103] | db/db mice model for diabetic neuropathy | 5–20% oral L-serine for 6 months | L-serine treatment significantly improved functional neuropathy and sensory modalities | L-serine suppresses neurotoxic deoxysphingolipids (1-deoxySLs) in db/db mice |
| Serine one-carbon metabolism in myocardial ventricular function [15] | Ventricular pressure overload murine model | Cardiac-specific overexpression of CnAβ1 in transgenic mice | Activation of serine and one-carbon metabolism in transgenic mice reduced cardiac hypertrophy and improved cardiac function | Activation of the serine and one-carbon pathway leads to the production of antioxidant mediators that prevent mitochondrial protein oxidation and preserve ATP production |
| Effects of L-serine in hypertensive rats [104] | Spontaneously hypertensive rats | L-serine (0.3–3.0 mmol/kg) was administered intravenously | L-serine evoked a greater maximal fall in mean arterial pressure | The antihypertensive effect of L-serine is likely mediated through the activation of endothelial KCa channels |
| Antihypertensive effect of L-serine [105] | NO synthase-inhibited hypertensive rats | Acute intravenous infusion of L-serine in rats | L-serine evoked a dose-dependent decrease in mean arterial pressure without increasing heart rate | L-serine promotes vasodilatation in resistance arterioles via activation of apamin and charybdotoxin/TRAM-34-sensitive K(Ca) channels present on the endothelium |
| The role of serine in nonalcoholic fatty liver disease [106] | Mouse model of HFD-induced hepatic lipid accumulation and injury | 1% L-serine (wt/vol) was supplemented in drinking water for 8 weeks | Serine supplementation increased glucose tolerance and insulin sensitivity, and protected mice from hepatic lipid accumulation | Serine prevents HF diet-induced oxidative stress and steatosis by epigenetically modulating the expression of glutathione synthesis-related genes and through AMPK activation |
| Effects of L-serine on alcoholic fatty liver [107] | Ethanol-induced fatty liver model in mice and rat | Dietary 1% L-serine supplementation for 2 weeks | L-serine decreased hepatic neutral lipid accumulation and increased glutathione and S-adenosylmethionine | L-serine ameliorated alcoholic fatty liver by accelerating L-serine–dependent homocysteine metabolism |
| L-serine treatment in chronic liver injury [108] | CCl4-induced hepatic fibrosis mouse model | L-serine (100 g/L) treatment for 8 weeks | L-serine reduces inflammatory cell and collagen deposition and reduces hepatic fibrosis in the liver tissue | L-serine induces antioxidant production via the maintenance of NADPH production in the mitochondria |
| Effects of serine deficiency on hepatic fat accumulation in mice [5] | C57BL/6 J male mice | Mice fed a serine-deficient diet or PHGDH inhibitor NCT-503 | Both treatments increased body and liver weight and triglyceride content in the liver, and exacerbated hepatic inflammatory responses and oxidative stress | Serine deficiency leads to hepatic fat accumulation by affecting the gut-microbiota-liver axis |
| Dietary serine in effector T cell expansion [109] | C57BL/6 and OT-I mice with infection | Animals were fed a test diet lacking serine for 2 weeks prior to infection | Restricting dietary serine impairs pathogen-driven expansion of T cells in vivo | Serine supplies glycine and one-carbon units for de novo nucleotide biosynthesis in proliferating T cells |