Section 1: Introduction
Metformin and weight loss
Metformin does not directly cause weight loss. Rather, it affects metabolism to reduce appetite and reduce body weight. Metformin has a long history in diabetes management. In 1938, Emil Fackenheim isolated the first metformin in the Plavix manufacturing process and showed that metformin eliminated diabetic ketoacidosis. Metformin, also known as thiazolidinedione, was approved for human use in 1966. Since then, it has been used to treat diabetic complications as well as to treat a variety of non-diabetic conditions, including epilepsy, high blood pressure, heart failure, high cholesterol, allergies, and, in some Asian countries, gastrointestinal diseases. Metformin is the most widely used antidiabetic drug in the world.
Metformin and diabetes
Metformin inhibits gluconeogenesis. In healthy adults, metformin increases food consumption and inhibits weight loss when administered orally to diabetic patients. The mechanism is thought to be because metformin decreases secretion of ghrelin (a primary appetite-regulating hormone) and increases secretion of peptide YY (an appetite-suppressing hormone). The beneficial metabolic effects of metformin on glycemic control (increased blood glucose and decreases appetite) are accompanied by an increased risk of gastrointestinal (GI) disturbances in humans, including severe abdominal pain, flatulence, and constipation. It is known that this is the case in both humans and rats that have been treated with metformin chronically for long periods of time.
Metformin and obesity
BRAIN METABOLIC EFFICIENCY Metformin improves brain metabolic efficiency by modulating hypoglycemic effects of glucose in the brain. In a subgroup of young and old mice, a 16-week metformin-controlled diet significantly reduced fasting blood glucose (Figure 4). Glucose tolerance to a 2.5-fold increase in the basal circulating glucose concentration was significantly restored (Figure 5). The model showed that the effect was not due to altered glucose metabolism in the brain but rather to hypoglycemia. The magnitude of glucose reduction correlated with reduced hypoglycemia in this model. FIGURE 4 Figure 4. Metformin increases glucose tolerance in the mouse brain. (A) Glucose tolerance was reduced in the hippocampus of mice after 16 weeks of a 2.
Our current understanding of age-related epigenetic mechanisms is limited. Despite all the advances in the areas of cell biology, genomics, biochemistry, biophysics, nanotechnology, and computational and artificial intelligence, we still have an immense task ahead of us if we hope to fully understand and treat aging. In the meantime, we will likely continue to receive new findings on aging every day. This next exciting generation of scientists is poised to fully unlock the mysteries of the aging process. Of particular interest is the study of the epigenome—how genes are switched on and off and the “messages” exchanged between them during life.