This review explores the physiological and molecular effects of caloric restriction (CR), exercise, and pharmacological mimetics on aging and metabolic health. CR has been shown to extend both mean and maximum lifespan in animal models by activating stress response pathways and enhancing mitochondrial function. Exercise primarily improves healthspan, delaying the
This 2021 review article explores the multifaceted role of metformin in modulating autophagy across various biological systems. Metformin primarily induces autophagy through activation of AMP-activated protein kinase (AMPK), leading to inhibition of the mTOR pathway. It also influences other signaling pathways, including AMPK/CEBPD, MiTF/TFE, AMPK/ULK1, and AMPK/miR-221. Additionally, metformin can
This study investigates the effects of alpha-lipoic acid (ALA) on lung cancer growth. The findings show that ALA inhibits lung cancer cell proliferation by blocking mTOR signaling, which in turn suppresses autophagy, a process essential for cancer cell survival. The study suggests that ALA may be a promising therapeutic agent
This randomized, single-blind, placebo-controlled trial evaluated the impact of metformin on longevity-associated pathways in 38 prediabetic individuals over two months. Participants received either metformin (1500 mg/day) or placebo. Metformin treatment led to significant improvements in metabolic parameters and insulin sensitivity. Notably, there was an increase in SIRT1 gene and protein
This review explores metformin’s potential as an anti-aging therapy, highlighting its modulation of key aging-related pathways such as AMPK activation, mTOR inhibition, and IGF-1 signaling reduction. Preclinical studies demonstrate metformin’s ability to extend lifespan and healthspan in various organisms. Observational data suggest reduced incidence of age-related diseases in metformin users.
This 2010 article by Mikhail V. Blagosklonny proposes a translational framework to extend healthy lifespan by pharmacologically suppressing aging. The author introduces the concept of “post-aging syndrome,” where age-related diseases are delayed or prevented through targeted interventions. Central to this approach is the inhibition of the mTOR pathway, which is
This review explores the complex biological processes underlying healthy aging and extended lifespan. It emphasizes the roles of genetic and environmental factors, highlighting key pathways such as insulin/IGF-1, mTOR, AMPK, and sirtuins in regulating aging. The article discusses mechanisms like oxidative stress, mitochondrial dysfunction, cellular senescence, and stem cell exhaustion
This 2023 article by Mikhail V. Blagosklonny explores the classification of menopause, aging, and prostate cancer as diseases through the lens of the hyperfunction theory of aging. While prostate cancer is universally recognized as a disease, the author argues that menopause, despite being a natural process, is also a disease
This 2018 phase 2a randomized, placebo-controlled clinical trial evaluated the effects of selective TORC1 inhibition on immune function in 264 elderly participants. The study administered a low-dose combination of BEZ235 (a catalytic mTOR inhibitor) and RAD001 (everolimus, an allosteric mTOR inhibitor) for 6 weeks. Results showed a significant reduction in
This 2019 study published in Cell Reports investigates the role of autophagy activation in promoting hair growth. Researchers found that compounds such as rapamycin, metformin, α-ketoglutarate (α-KG), and α-ketobutyrate (α-KB) stimulate the transition of hair follicles from the telogen (resting) to the anagen (growth) phase by activating autophagy. Inhibition of
