Theories of Aging and Chronic Diseases: Chronic Inflammation an Interdependent ‘Roadmap’ to Age-Associated Illnesses

Cancer; an induced disease of twentieth century! Induction of tolerance, increased entropy and ‘Dark Energy’: loss of biorhythms (Anabolism v. Catabolism)

“…Stimuli-induced expression of TLRs contributes to the differential recognition of molecular structures or sub-structures of pathogens for specific sensitization and activation of APCs and appropriate response. The important roles that TLRs, decoy (dRs) or pattern recognition receptor molecules (PRRs) play in defense of body for activation of innate or adaptive immune or non-immune pathways for generation of death factors, pro-, and anti-inflammatory responses for human development or initiation or termination of acute or chronic inflammatory processes, immune tolerance and cancer have been extensively studied [ 5 , 7 , 39 , 67 , 72 , 79 , 157 – 162 , 191 , 194 – 207 , 210 – 217 ].…”

“…In the last six decades significant increased in soft tissue B cell-derived lymphomas (e.g., aggressive or non-aggressive forms of acute leukemia, lymphocytic leukemia, Burkett’s’ lymphoma, myelocytic leukemia, EBV-positive large B cell lymphoma in elderly, germinal center lymphoma or Kaposi sarcoma-associated herpes virus-encoded proteins in lymphoma) as well as solid tumors (e.g., liver, lung, breast, prostate, thyroid, pancreas, colon, ovarian) have been reported [ 5 , 7 , 13 , 16 , 20 , 67 , 72 , 89 , 101 , 175 , 223 ].…”

“…The immune composition in gut-associated lymphoid tissues (GALTs) shares some features with other tissues that are responsible for confronting and combating external harmful agents. Examples of such tissues are the skin, respiratory lung-associated lymphoid tissues (LALTs) or conjunctival-associated lymphoid tissues (CALTs) that are targets for early sensitization and tolerance (induction of Th2 phenotypes) against perennial allergens (e.g., dust mites, cat epithelium or certain environmental components) [ 5 , 7 , 8 , 31 , 36 – 41 , 64 , 69 , 72 , 79 , 80 , 83 , 101 , 106 , 137 , 156 ]. The special features of immunity and tolerization in GALTs (e.g., increased numbers of plasma cells lining of the gut epithelium for production of IgA and IgE, TLRs, enzymes and hormones) are required for maintenance of homeostasis of gut microbiota (intrinsic foreign elements) and ingested foods.…”

“…The special features of immunity and tolerization in GALTs (e.g., increased numbers of plasma cells lining of the gut epithelium for production of IgA and IgE, TLRs, enzymes and hormones) are required for maintenance of homeostasis of gut microbiota (intrinsic foreign elements) and ingested foods. In the gastrointestinal tract, tolerance against various GI bacteria (GI flora) is likely due to several regulatory/inhibitory complex molecules with IRAK-M and related immune suppressive pathways (e.g., dILRs, TNFRs or surface molecules receptors) [ 5 – 8 , 36 – 41 , 64 , 69 , 72 , 79 , 142 ]. Interestingly, expression of regulatory receptor molecules (IRAK-M) in epithelial lung tissue of asthmatic patients suggests induction of immune suppression also involves expression of adenosine receptors (A2A) and surface molecules of CD4 + T lymphocytes that could signal for mitochondrial shutdown to prevent damage to the tissue [ 5 , 79 , 142 ].…”

“…Review of a number of reports also suggests that insulin-insensitivity and hyperglycemia (glucose toxicity and high circulating glucose levels) alter mTOR complexes (mTORC1, mTORC2) and mediate several interdependent pathways of metabolism, ribosomal biogenesis and autophagy. Whether caloric restriction (CR) and increased insulin sensitivity via decreased signaling in mTOR pathways, promotes endocrine factors and lifespan are subjects of recent debates [ 5 , 72 , 79 , 202 – 207 ].…”