Aging Body the Author Bases

Aging Body

The author bases his understanding of osteoporosis in humans on the research data from experiments with rodents, which shows estrogen deficiency triggers osteoclast activity. Increased osteoclast activity is another way of stating that bone is being resorbed or lost. When combined with a mild decrease in T cell tolerance to self-antigens, which is an immune response directed against one's own tissues, an autoimmune disorder affecting bone develops. The reason the author suspects this process is occurring is because the same process occurs in mothers immediately following delivery. Bone resorption is triggered by lower levels of estrogen, in order to supply sufficient calcium for the mother's milk.

Steps leading to atherosclerosis:

The inner walls of blood vessels (lumen) become 'sticky', because the vascular endothelium expresses molecules that promote adhesion to blood cells (Libby, Ridker, and Hansson, 2011). Normally, blood cells do not attach to the walls of blood vessels, but in the presence of irritating conditions, such as high cholesterol levels, high blood pressure, or chronic inflammation, these adhesion molecules may be expressed.

b. Blood vessels also become more permeable to cholesterol. This results in the entry and retention of cholesterol into the walls of the blood vessels (intima).

c. The macrophage, a type of immune cell, will attach to blood vessel walls through the adhesion molecules and enter. Upon entry, they will transform into phagocytes or macrophages, which are a type of cell that consumes cellular debris, tumor cells, and pathogens for destruction. In the presence of cholesterol, the macrophages will accumulate cholesterol.

d. Additional immune cells will be attracted by the cholesterol-bloated macrophages (foam cells), including T cells, resulting in the formation of an atheromatous lesion or atherosclerotic plaque.

e. Smooth muscle cells in the intima begin to produce structural proteins that form a fibrous cap over the plaque.

f. Over time, the plaque grows in size due to the accumulation of foam cells. Some of these foam cells die and release cholesterol into the lesion, forming a zone in the center of the plaque devoid of living tissue and filled with lipids. Blood flow may eventually become restricted (stenosis) enough to cause tissue death (ischaemia). If the plaque dislodges (embolize) and begins to migrate through the blood vessels, it can lodge in another location and cause local tissue death (thrombosis).

3. Growth factors can induce apoptosis by binding to their respective receptors (RTKs). When activated, RTKs in turn activate the Ras, Raf, MEK, MAPK, MKK, ERK, Fos, JNKs, and Jun pathway, which can lead to the induction of ARF via gene upregulation. ARF in turn suppresses mdm2, a suppressor of p53 activity. The resulting increase in p53 activity can induce Bax, Mt, and thus apoptosis.

4. Adenomatous familial polyposis is caused by a truncated APC protein, which results from inherited mutations in the APC gene (Segditsas and Tomlinson, 2006). However, the activity of the wild-type or normal APC allele is usually sufficient to maintain tumor suppressor activity. For this reason, and because the wild-type allele is often found to have acquired somatic mutations, it is assumed that both alleles must be mutated before tumors can form. The vast majority of mutations found in colorectal tumors have retained 0 to 3 20-amino acid repeats, suggesting APC proteins that retain some ?-catenin binding activity result most often in tumor formation. The following describes the steps believed to occur from inheriting a mutated APC allele to the formation of cancer: