Exercise mimetic

Last updated
Various exercise mimetics and their effects on pathways also affected by exercise Multiple tissues and organ systems are affected by exercise, initiating diverse homeostatic responses.jpg
Various exercise mimetics and their effects on pathways also affected by exercise

An exercise mimetic is a drug that mimics some of the biological effects of physical exercise. Exercise is known to have an effect in preventing, treating, or ameliorating the effects of a variety of serious illnesses, including cancer, type 2 diabetes, cardiovascular disease, and psychiatric and neurological diseases such as Alzheimer's disease. As of 2021, no drug is known to have the same benefits. [2] [3] [1]

Known biological targets affected by exercise have also been targets of drug discovery, with limited results. These known targets include: [2]

TargetsDrug candidates
irisin [2]
brain-derived neurotrophic factor [2]
interleukin-6 [2]
peroxisome proliferator-activated receptor delta GW501516 [2]
PPAR gamma coactivator 1-alpha [4]
estrogen-related receptor γ GSK4716 [2]
NFE2L2 [4]
Canonical transient receptor potential (TRPC) proteins [5]
Myostatin myostatin inhibitors [6]

The majority of the effect of exercise in reducing cardiovascular and all-cause mortality cannot be explained via improvements in quantifiable risk factors, such as blood cholesterol. This further increases the challenge of developing an effective exercise mimetic. [1] Moreover, even if a broad spectrum exercise mimetic were invented, it is not necessarily the case that its public health effects would be superior to interventions to increase exercise in the population. [1]

Related Research Articles

<span class="mw-page-title-main">Type 2 diabetes</span> Type of diabetes mellitus with high blood sugar and insulin resistance

Type 2 diabetes (T2D), formerly known as adult-onset diabetes, is a form of diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. Common symptoms include increased thirst, frequent urination, fatigue and unexplained weight loss. Symptoms may also include increased hunger, having a sensation of pins and needles, and sores (wounds) that do not heal. Often symptoms come on slowly. Long-term complications from high blood sugar include heart disease, strokes, diabetic retinopathy which can result in blindness, kidney failure, and poor blood flow in the limbs which may lead to amputations. The sudden onset of hyperosmolar hyperglycemic state may occur; however, ketoacidosis is uncommon.

<span class="mw-page-title-main">Statin</span> Class of drugs used to lower cholesterol levels

Statins, also known as HMG-CoA reductase inhibitors, are a class of lipid-lowering medications that reduce illness and mortality in those who are at high risk of cardiovascular disease. They are the most commonly prescribed cholesterol-lowering drugs.

Life extension is the concept of extending the human lifespan, either modestly through improvements in medicine or dramatically by increasing the maximum lifespan beyond its generally-settled limit of 125 years. Several researchers in the area, along with "life extensionists", "immortalists", or "longevists", postulate that future breakthroughs in tissue rejuvenation, stem cells, regenerative medicine, molecular repair, gene therapy, pharmaceuticals, and organ replacement will eventually enable humans to have indefinite lifespans through complete rejuvenation to a healthy youthful condition (agerasia). The ethical ramifications, if life extension becomes a possibility, are debated by bioethicists.

<span class="mw-page-title-main">Exercise</span> Bodily activity intended to improve health

Exercise is intentional physical activity to enhance or maintain fitness and overall health.

<span class="mw-page-title-main">Metformin</span> Medication used to treat diabetes by reducing glucose levels

Metformin, sold under the brand name Glucophage, among others, is the main first-line medication for the treatment of type 2 diabetes, particularly in people who are overweight. It is also used in the treatment of polycystic ovary syndrome. It is sometimes used as an off-label adjunct to lessen the risk of metabolic syndrome in people who take antipsychotics. Metformin is not associated with weight gain and is taken by mouth.

<span class="mw-page-title-main">Aerobic exercise</span> Low to high intensity physical exercise

Aerobic exercise is physical exercise of low to high intensity that depends primarily on the aerobic energy-generating process. "Aerobic" is defined as "relating to, involving, or requiring oxygen", and refers to the use of oxygen to meet energy demands during exercise via aerobic metabolism adequately. Aerobic exercise is performed by repeating sequences of light-to-moderate intensity activities for extended periods of time. Examples of cardiovascular or aerobic exercise are medium- to long-distance running or jogging, swimming, cycling, stair climbing and walking.

<span class="mw-page-title-main">Cardiovascular disease</span> Class of diseases that involve the heart or blood vessels

Cardiovascular disease (CVD) is any disease involving the heart or blood vessels. CVDs constitute a class of diseases that includes: coronary artery diseases, heart failure, hypertensive heart disease, rheumatic heart disease, cardiomyopathy, arrhythmia, congenital heart disease, valvular heart disease, carditis, aortic aneurysms, peripheral artery disease, thromboembolic disease, and venous thrombosis.

<span class="mw-page-title-main">Hypertriglyceridemia</span> High triglyceride blood levels

Hypertriglyceridemia is the presence of high amounts of triglycerides in the blood. Triglycerides are the most abundant fatty molecule in most organisms. Hypertriglyceridemia occurs in various physiologic conditions and in various diseases, and high triglyceride levels are associated with atherosclerosis, even in the absence of hypercholesterolemia and predispose to cardiovascular disease.

<span class="mw-page-title-main">High-intensity interval training</span> Exercise strategy

High-intensity interval training (HIIT) is a training protocol alternating short periods of intense or explosive anaerobic exercise with brief recovery periods until the point of exhaustion. HIIT involves exercises performed in repeated quick bursts at maximum or near maximal effort with periods of rest or low activity between bouts. The very high level of intensity, the interval duration, and number of bouts distinguish it from aerobic (cardiovascular) activity, because the body significantly recruits anaerobic energy systems. The method thereby relies on "the anaerobic energy releasing system almost maximally".

<span class="mw-page-title-main">Diabetic nephropathy</span> Chronic loss of kidney function

Diabetic nephropathy, also known as diabetic kidney disease, is the chronic loss of kidney function occurring in those with diabetes mellitus. Diabetic nephropathy is the leading causes of chronic kidney disease (CKD) and end-stage renal disease (ESRD) globally. The triad of protein leaking into the urine, rising blood pressure with hypertension and then falling renal function is common to many forms of CKD. Protein loss in the urine due to damage of the glomeruli may become massive, and cause a low serum albumin with resulting generalized body swelling (edema) so called nephrotic syndrome. Likewise, the estimated glomerular filtration rate (eGFR) may progressively fall from a normal of over 90 ml/min/1.73m2 to less than 15, at which point the patient is said to have end-stage renal disease. It usually is slowly progressive over years.

The term diabetes includes several different metabolic disorders that all, if left untreated, result in abnormally high concentrations of a sugar called glucose in the blood. Diabetes mellitus type 1 results when the pancreas no longer produces significant amounts of the hormone insulin, usually owing to the autoimmune destruction of the insulin-producing beta cells of the pancreas. Diabetes mellitus type 2, in contrast, is now thought to result from autoimmune attacks on the pancreas and/or insulin resistance. The pancreas of a person with type 2 diabetes may be producing normal or even abnormally large amounts of insulin. Other forms of diabetes mellitus, such as the various forms of maturity-onset diabetes of the young, may represent some combination of insufficient insulin production and insulin resistance. Some degree of insulin resistance may also be present in a person with type 1 diabetes.

Interval training is a type of training exercise that involves a series of high-intensity workouts interspersed with rest or break periods. The high-intensity periods are typically at or close to anaerobic exercise, while the recovery periods involve activity of lower intensity. Varying the intensity of effort exercises the heart muscle, providing a cardiovascular workout, improving aerobic capacity and permitting the person to exercise for longer and/or at more intense levels.

Intestinal permeability is a term describing the control of material passing from inside the gastrointestinal tract through the cells lining the gut wall, into the rest of the body. The intestine normally exhibits some permeability, which allows nutrients to pass through the gut, while also maintaining a barrier function to keep potentially harmful substances from leaving the intestine and migrating to the body more widely. In a healthy human intestine, small particles can migrate through tight junction claudin pore pathways, and particles up to 10–15 Å can transit through the paracellular space uptake route. There is some evidence abnormally increased intestinal permeability may play a role in some chronic diseases and inflammatory conditions. The most well understood condition with observed increased intestinal permeability is celiac disease.

Performance-enhancing substances, also known as performance-enhancing drugs (PEDs), are substances that are used to improve any form of activity performance in humans. A well-known example of cheating in sports involves doping in sport, where banned physical performance-enhancing drugs are used by athletes and bodybuilders. Athletic performance-enhancing substances are sometimes referred as ergogenic aids. Cognitive performance-enhancing drugs, commonly called nootropics, are sometimes used by students to improve academic performance. Performance-enhancing substances are also used by military personnel to enhance combat performance.

Intermittent fasting is any of various meal timing schedules that cycle between voluntary fasting and non-fasting over a given period. Methods of intermittent fasting include alternate-day fasting, periodic fasting such as the 5:2 diet, and daily time-restricted eating (TRE).

Glucagon-like peptide-1 (GLP-1) receptor agonists, also known as GLP-1 analogs, GLP-1DAs or incretin mimetics, are a class of drugs that reduce blood sugar and energy intake by activating the GLP-1 receptor. They mimic the actions of the endogenous incretin hormone GLP-1 that is released by the gut after eating.

<span class="mw-page-title-main">Diabetes</span> Group of endocrine diseases characterized by high blood sugar levels

Diabetes mellitus, often known simply as diabetes, is a group of common endocrine diseases characterized by sustained high blood sugar levels. Diabetes is due to either the pancreas not producing enough insulin, or the cells of the body becoming unresponsive to the hormone's effects. Classic symptoms include thirst, polyuria, weight loss, and blurred vision. If left untreated, the disease can lead to various health complications, including disorders of the cardiovascular system, eye, kidney, and nerves. Untreated or poorly treated diabetes accounts for approximately 1.5 million deaths every year.

SGLT2 inhibitors, also called gliflozins or flozins, are a class of medications that inhibit sodium-glucose transport proteins in the nephron, unlike SGLT1 inhibitors that perform a similar function in the intestinal mucosa. The foremost metabolic effect of this is to inhibit reabsorption of glucose in the kidney and therefore lower blood sugar. They act by inhibiting sodium-glucose transport protein 2 (SGLT2). SGLT2 inhibitors are used in the treatment of type 2 diabetes. Apart from blood sugar control, gliflozins have been shown to provide significant cardiovascular benefit in people with type 2 diabetes. As of 2014, several medications of this class had been approved or were under development. In studies on canagliflozin, a member of this class, the medication was found to enhance blood sugar control as well as reduce body weight and systolic and diastolic blood pressure.

<span class="mw-page-title-main">Caffeine use for sport</span> Caffeine as a legal performance enhancer in sport

Caffeine use for sport is a worldwide known and tested idea. Many athletes use caffeine as a legal performance enhancer, as the benefits it provides, both physically and cognitively outweigh the disadvantages. The benefits caffeine provides influences the performance of both endurance athletes and anaerobic athletes. Caffeine has been proven to be effective in enhancing performance.

The benefits of physical activity range widely. Most types of physical activity improve health and well-being.

References

  1. 1 2 3 4 Hawley, John A.; Joyner, Michael J.; Green, Daniel J. (February 2021). "Mimicking exercise: what matters most and where to next?". The Journal of Physiology. 599 (3): 791–802. doi: 10.1113/JP278761 . ISSN   0022-3751. PMC   7891316 . PMID   31749163.
  2. 1 2 3 4 5 6 7 Jang, Young Jin; Byun, Sanguine (31 December 2021). "Molecular targets of exercise mimetics and their natural activators". BMB Reports. 54 (12): 581–591. doi: 10.5483/BMBRep.2021.54.12.151 . ISSN   1976-6696. PMC   8728540 . PMID   34814977.
  3. Febbraio, Mark A. (February 2017). "Health benefits of exercise — more than meets the eye!". Nature Reviews Endocrinology. 13 (2): 72–74. doi:10.1038/nrendo.2016.218. ISSN   1759-5037. PMID   28051119. S2CID   5824789.
  4. 1 2 Cento, Alessia S.; Leigheb, Massimiliano; Caretti, Giuseppina; Penna, Fabio (October 2022). "Exercise and Exercise Mimetics for the Treatment of Musculoskeletal Disorders". Current Osteoporosis Reports. 20 (5): 249–259. doi: 10.1007/s11914-022-00739-6 . hdl: 2434/936387 . PMID   35881303.
  5. Numaga-Tomita, Takuro; Oda, Sayaka; Nishiyama, Kazuhiro; Tanaka, Tomohiro; Nishimura, Akiyuki; Nishida, Motohiro (March 2019). "TRPC channels in exercise-mimetic therapy". Pflügers Archiv - European Journal of Physiology. 471 (3): 507–517. doi: 10.1007/s00424-018-2211-3 . PMC   6515694 . PMID   30298191.
  6. Allen, David L.; Hittel, Dustin S.; McPherron, Alexandra C. (October 2011). "Expression and Function of Myostatin in Obesity, Diabetes, and Exercise Adaptation". Medicine and Science in Sports and Exercise. 43 (10): 1828–1835. doi: 10.1249/MSS.0b013e3182178bb4 . ISSN   0195-9131. PMC   3192366 . PMID   21364474.