![]() Uncoupling protein 1 of brown adipocytes, the only uncoupler: a historical perspective. Aging leads to a programmed loss of brown adipocytes in murine subcutaneous white adipose tissue. Mechanisms of aging-related impairment of brown adipocyte development and function. Rapamycin, Acarbose and 17α-estradiol share common mechanisms regulating the MAPK pathways involved in intracellular signaling and inflammation. Cap-independent translation: a shared mechanism for lifespan extension by rapamycin, acarbose, and 17α-estradiol. The MalR type regulator AcrC is a transcriptional repressor of acarbose biosynthetic genes in Actinoplanes sp. Beneficial effects of acarbose on daily plasma glucose profile and cataract development in sand rats. Effect of miglitol and acarbose on starch digestion, daily plasma glucose profiles and cataract formation. Intranasal rapamycin ameliorates Alzheimer-like cognitive decline in a mouse model of Down syndrome. mTOR drives cerebral blood flow and memory deficits in LDLR(-/-) mice modeling atherosclerosis and vascular cognitive impairment. Low-dose oral sirolimus reduces atherogenesis, vascular inflammation and modulates plaque composition in mice lacking the LDL receptor. Rapamycin inhibits osteolysis and improves survival in a model of experimental bone metastases. Rapamycin partially mimics the anticancer effects of calorie restriction in a murine model of pancreatic cancer. mTOR is a key modulator of ageing and age-related disease. ![]() Johnson SC, Rabinovitch PS, Kaeberlein M. Dietary restriction and lifespan: lessons from invertebrate models. Discovery of canagliflozin, a novel C-glucoside with thiophene ring, as sodium-dependent glucose cotransporter 2 inhibitor for the treatment of type 2 diabetes mellitus. Interaction of the sodium/glucose cotransporter (SGLT) 2 inhibitor canagliflozin with SGLT1 and SGLT2. Rapamycin-mediated lifespan increase in mice is dose and sex dependent and metabolically distinct from dietary restriction. Rapamycin, but not resveratrol or simvastatin, extends life span of genetically heterogeneous mice. Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Longer lifespan in male mice treated with a weakly estrogenic agonist, an antioxidant, an α-glucosidase inhibitor or a Nrf2-inducer. Acarbose, 17-α-estradiol, and nordihydroguaiaretic acid extend mouse lifespan preferentially in males. Miller RA, et al. Canagliflozin extends life span in genetically heterogeneous male but not female mice. Caloric restriction improves health and survival of rhesus monkeys. A 2-year randomized controlled trial of human caloric restriction: feasibility and effects on predictors of health span and longevity. Extending healthy life span-from yeast to humans. We propose that these changes may be a part of a shared common pathway that is seen in slow-aging mice whether the delayed aging is due to a mutation, a low-calorie diet, or a drug.įontana L, Partridge L, Longo VD. We have previously shown that the same suite of changes is seen in each of four varieties of slow-aging single-gene mutant mice. Each of these proteins is thought to play a role in one or more age-related diseases, including metabolic, inflammatory, and neurodegenerative diseases. These shared traits include an increase in uncoupling protein UCP1 in brown fat and in subcutaneous and intra-abdominal white fat, a decline in proinflammatory M1 macrophages and corresponding increase in anti-inflammatory M2 macrophages, an increase in muscle fibronectin type III domain containing 5 (FNDC5) and its cleavage product irisin, and higher levels of doublecortin (DCX) and brain-derived neurotrophic factor (BDNF) in brain. We show here that these four drugs, as well as a calorie-restricted diet, can induce a common set of changes in fat, macrophages, plasma, muscle, and brain when evaluated in young adults at 12 months of age. Average and maximal lifespan can be increased in mice, in one or both sexes, by four drugs: rapamycin, acarbose, 17a-estradiol, and canagliflozin.
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