Diseases
Effector mechanisms mediating the age-associated disorders
Effector mechanisms mediating the age-associated disorders
Effector mechanisms mediating the age-associated disorders
Effector mechanisms mediating the age-associated disorders
Effector mechanisms mediating the age-associated disorders
IIS/TOR signaling and AMPK Mitochondrial dysfunction Genomic damage and telomere degradation Autophagy Defection Inflammation response
Cardiovascular Resistance to Insulin can cause abnormality function in the cardiac system (S.-Y. Park et al., 2005) Downregulation of insulin, TOR and AMPK can prevent cardiovascular disease (Hernández et al., 2011)
Defective mitochondria lead to cardiomyocyte apoptosis (Crow, Mani, Nam, & Kitsis, 2004)
Induce endothelial senescence leading to atherosclerosis (Minamino & Komuro, 2002)
Autophagy failure can stimulate Cardiomyopathy and cardiac hypertrophy (Fidziańska, Bilińska, Walczak, Witkowski, & Chojnowska, 2010)
CRP and fibrinogen rise in plasma can lead to cardiovascular disorders (Coppola et al., 2006)
Neurodegenerative
Longevous IIS mutants as well as decreasing of IIS signaling can play a role in some nervous system dysfunction (Broughton & Partridge, 2009; O’Neill, Kiely, Coakley, Manning, & Long-Smith, 2012)
Impairment in function ais associated and promote pathology, especially in PDs (Moon & Paek, 2015)
Neuron death related to damaging DNA structure has a role in neurodegenerative diseases (Kruman et al., 2004). Telomere engaging is unknown
Accumulation of toxic proteins due to autophagy flaw can associate with neuropathology (Fang, Gu, Smerin, Mao, & Xiong, 2017; Nixon & Yang, 2011; Schöndorf et al., 2014)
Reducing in brain size seen due to increased amount of IL-6, TNF-α, and CRP in plasma (Ishikawa, Kobayashi, Fujii, & Kobayashi, 2015; Tan et al., 2007)
Type II Diabetes
IIS inhibition in peripheral tissues, leading to insulin resistance associated with the pathology of diabetes (Ohshima et al., 2012)
Oxidative stress and mitochondrial dysfunction (M Victor, Rocha, Herance, & Hernandez-Mijares, 2011), decline ATP production leading to insulin resistance (Veech, 2004)
There is a direct association between oxidative DNA damage and the complications of diabetes (Hinokio et al., 1999)
Defects in autophagy lead to pancreatic beta cell dysfunction (Marchetti & Masini, 2009), insulin resistance and accumulation of toxic molecules (Yang, Li, Fu, Calay, & Hotamisligil, 2010)
the higher levels of pro inflammatory cytokines, IL-6, TNF-α, and CRP can increase insulin resistance (Mirza et al., 2012)
Cancers
Downregulation of IIS and TOR signaling suppresses tumors (Partridge, Alic, Bjedov, & Piper, 2011)
Mutation in mtDNA and an increase in mitochondrial ROS are oncogenic factors (H.-C. Lee, Chang, & Chi, 2010)
Rambunctious growth as well as accumulated numerous mutations in cancer cells can be caused by DDR defects (Menendez et al., 2011), Telomere shortening could be related to senescence of tumor suppressor (Bruunsgaard, Pedersen, & Pedersen)
Autophagy protects initial steps of tumor growth and makes cancer cells spread (Pavlides et al., 2012)
TNF-α, IL-6 and cyclooxygenase play a key role (Willcox et al.)
Rheumatoid Arthritis
TOR signaling inhibition has a protective effect (Malemud, 2015)
Leaks in the respiratory chain create ROS and lead to atherosclerosis by multiple pathways (Hulsmans, Van Dooren, & Holvoet, 2012)
A decrease in DDR may be related to disease progresses (S.-H. Lee et al., 2003)
A defect in lysosomal degradation system (autophagy) or ubiquitin–proteasomal regulation causes joint inflammatory disorders (N.-Y. Lin et al., 2013)
Antigen-specific immune responses by T-lymphocyte, Cytokine signaling network(T-cell-independent), and invasive function like a tumor play roles in this disease (Phillips, Dias, Kitas, & Griffiths, 2010)
Sarcopenia
اyperactivation  of mTOR leads to skeletal muscle fibers damage in aged people (H. Tang et al., 2019), up-regulated MAPK signaling contributing to the impaired regeneration a (Carlson et al., 2009)
Oxidative stress, altered mitochondrial dynamics, change in mitochondrial turnover and induce mitochondrion-mediated apoptosis (Derbré, Gratas-Delamarche, Gómez-Cabrera, & Viña, 2014)
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Accumulation of toxic proteins due to autophagy defects can cause the pathology (Masiero & Sandri, 2010)
An increased amount of TNF-α, IL-6, and also CRP in plasma enhances problems in muscle mass, strength, and catabolism (Schaap, Pluijm, Deeg, & Visser, 2006)
Osteoporosis
Over-active osteoclasts (TOR-dependent) cause osteoporosis (Blagosklonny, 2008)
mtDNA deletions and mitochondrial ROS promot pathology (Abdollahi, Larijani, Rahimi, & Salari, 2005)
An increase in IL-6, TNFα, and RANKL by persistent cellular DNA damage (Blair & Athanasou, 2004)
Decreased autophagic activity in osteocytes (Blair & Athanasou, 2004) and increase apoptosis of mature osteoblasts and osteocytes
High levels of some interleukins (1,6,11,15 and 17) and TNF-α have key roles in pathology progression (Mundy, 2007)