Scientists are in search of drugs to reverse the aging process. Some are new; while others repurposed for diabetes or cancer may serve this purpose.
Senescent cells, thought to be responsible for many of the deadliest conditions associated with ageing, have become a focus. Drugs designed to target these senescent cells have been proven to extend lifespan in mice studies.
Metformin
Metformin (marketed under the brand name Glucophage) is widely prescribed to treat type 2 diabetes and gestational diabetes during gestation. Additionally, this OTC medication for weight loss may extend life and healthspan by slowing cellular aging processes. Researchers have recently found evidence suggesting it may also extend longevity by inhibiting cell division.
Metformin can reduce oxidative stress in cells, improve energy in them, stimulate autophagy and increase AMPK activity; as well as decreasing hepatic glucose production and improving insulin sensitivity while simultaneously decreasing mTOR activation and inflammation pathways – leading to longer cell lifespan and lessened aging.
Metformin extended mice lifespan by 25% by decreasing oxidative stress levels and increasing healthy mitochondria. It also helped lower cancer rates, angiogenesis and neurodegeneration rates significantly – evidence promising enough that in 2015 a clinical trial called Tame was launched to test whether metformin can slow biological aging while delaying age-related diseases onset.
Studies have demonstrated that Metformin can effectively decrease hepatic glucose production, improve insulin sensitivity and thus decrease blood sugar. Furthermore, Metformin also significantly reduced mTOR activation – one of the key players in the aging process – as well as decreasing cytokines that code for them and has anti-inflammatory effects; additionally it was observed to decrease fibrosis formation as well as amyloid plaque formation; these effects may be achieved via altering microbial folate and methionine metabolism, reduced reactive oxygen species production, changes to gene expression patterns and changes to epigenome changes.
Metformin can also reduce the risk of breast cancer through its ability to limit glucose uptake by cancer cells and convert it to glycolysis, decreasing both the Warburg effect and FAS expression, which provides fuel for cancer cell growth and metastasis. By doing so, metformin reduces cancer cell viability.
Scientists are exploring a variety of approaches to altering the biology of aging. A newly discovered class of drugs called “senolytics”, which block production of p53 protein, have shown dramatic longevity benefits in animal models; but research in this field remains in its infancy; researchers are exploring other potential interventions including using supplements, exercise and physical therapy, stem cells as repair systems or use stem cells to repair damage to cells or improve function in our bodies.
AMPK
AMPK (AMP-activated protein kinase) is an integral regulator of cell metabolism that senses energy stress and initiates responses that restore balance to maintain energy homeostasis. To achieve this goal, catabolic pathways should be utilized to increase ATP production while synthetic metabolic pathways should decrease its consumption. AMPK regulates several other cellular functions, such as autophagy, mitochondrial and lysosomal homeostasis, DNA repair and inflammatory signaling. As an attractive therapeutic target, direct activators of AMPK such as exercise, caloric restriction and metformin have been developed as potential therapeutic agents; some trials of such treatments are currently taking place; however it remains unknown which diseases benefit from activating this pathway and their long-term safety implications.
AMPK signaling pathway has been implicated in numerous physiological processes, including inflammation, aging and cancer. More specifically, its role in shifting macrophages toward anti-inflammatory M2 phenotype has recently come into focus as being particularly vital.
AMPK plays an essential role in macrophage polarisation and countering pro-inflammatory effects of glucocorticoids. Therefore, its activation may help enhance immunity function and protect against atherosclerosis and other inflammatory conditions.
AMPK signaling in cells is activated when an AMP molecule binds to its allosteric site and binds with non-catalytic subunit 1, where subsequent phosphorylation activates catalytic subunit 2 and downstream targets. Mutations disrupting activation have been associated with human metabolic disease and cardiac hypertrophy.
Natural compounds like curcumin and baicalein have been demonstrated to directly increase AMPK activity in cells, acting as AMP mimetics taken up by adenosine transporters and converted back into active form in the cell. They may also help decrease oxidative stress levels while increasing cholesterol efflux from macrophages thereby helping prevent atherosclerotic plaque formation.
AMPK, a highly conserved protein that regulates energy homeostasis in eukaryotic cells, has become increasingly recognized as an integral player in treating many human diseases. Studies have demonstrated its impact on mitochondrial and lysosomal energy production efficiency as well as on atherosclerotic lesions size reduction and tumour inhibition in mice models. Furthermore, this protein also plays a significant role in various other metabolic and physiological processes including lipid metabolism and macrophage polarisation processes.
Glucose
Glucose is one of the body’s primary fuel sources, alongside amino acids (the building blocks of protein) and fats. The brain relies on glucose for its functions – nerve cells need the energy provided by blood sugar for nerve transmissions and chemical messengers to function. Special cells in your pancreas monitor your blood glucose levels constantly and release insulin into the bloodstream to keep levels steady; insulin acts like a key that opens muscle, liver and fat cells so glucose can enter them to provide energy.
Nearly all living organisms create glucose from smaller starting materials through gluconeogenesis, an essential metabolic pathway. Starting with molecules with two to four carbon atoms and ending in glucose, photosynthesis is used by plants to produce energy via sunlight in order to make glucose. Humans and other animals produce it themselves using livers and kidneys as sites for this process.
Glycogenesis produces glucose as an integral building block for other vital biomolecules, including lactose – the main sugar found in milk – lactase (a disaccharide), polymers like starch and glycogen which serve as primary energy storage systems in our bodies; polymers of glucose may even serve as structural components in organs or tissues like skin, cellulose or chitin.
Glucose serves as a raw material in many other chemical reactions in the body, including production of hormones and vitamins such as Vitamin C necessary for tissue repair and wound healing. In addition, glucose acts as an intermediate in protein and lipid synthesis while adding glycosylation chains onto certain proteins or lipids is critical for their function; high blood glucose speeds this process up further leading to advanced Glycation End Products or AGEs being formed in higher quantities in bloodstream.
Interleukin-11
Researchers have discovered a potential target to reverse and extend human healthspan: IL-11 is an inflammatory cytokine elevated in several common diseases, such as cancer, fibrosis, multimorbidity and frailty – it also acts as a marker of aging; studies have demonstrated how decreasing its activity extends health span and lifespan in animal models while having numerous positive side effects for humans such as improving stem cell proliferation and inhibiting senescence.
Pleiotropic effects of IL-11 stem from its multidimensional role in multiple cellular processes, including proliferation, inflammation signalling, metabolism, ageing/senescence regulation via interactions with various pathways (ERK, AMPK and mTOR among them) that regulate ageing/senescence regulation; moreover IL-11 regulates GSK3b which is part of the phosphatidylinositol 3-kinase pathway and increases activity levels of another signalling molecule called Akt.
Inhibition of IL-11 significantly extends mouse lifespan and health by significantly decreasing senescence and improving their health and lifespan. Furthermore, this treatment protects against hepatitis C infection, renal injury and pulmonary fibrosis; mitigating liver damage while encouraging regeneration; increasing stem cells while decreasing oxidative stress levels and ultimately helping prevent diabetes by improving glucose tolerance and insulin sensitivity; mitigating liver damage while mitigating damage; protecting against liver cirrhosis as well as mitigating its symptoms.
Interleukin-11 (IL-11) has emerged as an attractive target for anti-aging medications, thanks to its role activating the AMPK signalling pathway and being associated with cell senescence, inflammation and fibrosis. IL-11 levels are upregulated in systemic sclerosis, rheumatoid arthritis, pulmonary fibrosis and inflammatory bowel disease – among others fibro-inflammatory conditions; it belongs to the IL-6 family but acts differently from other anti-fibro-inflammatory cytokines such as its fellow family member IL-6 in regards to activating this signalling pathway and being involved in cell senescence, inflammation and fibrosis.
Asperolide A is an innovative dipertenoid from marine algae that serves as an effective inhibitor of interleukin 11 (IL-11) and other proinflammatory mediators, while attenuating chemotherapy-induced inflammation responses. Furthermore, Asperolide A can significantly enhance muscle strength and vascular integrity among older mice; reduce hepatic steatosis/fibrosis/fibrosis as well as improve gastrointestinal function – all while significantly increasing survival in these models.
