cellular aging

what is one of the strongest independent risk factors for many chronic diseases such as cancer, Alzheimer’s, and ischemic heart disease

cellular aging

what is cellular aging the result of?

progressive decline in the lifespan and functional activity of cells, which reduces their ability to maintain normal tissue function over time

what are some abnormalities that contribute to the aging of cells?

• accumulation of DNA damage

• replicative senescence

• defective protein homeostasis

how can accumulation of DNA damage contribute to aging of cells?

defective DNA repair mechanisms results in accumulation of damage caused by free radicals over a prolonged period of time

how can replicative senescence contribute to aging of cells?

the reduced ability of cells to divide due to decreasing amounts of telomerase and progressive shortening of chromosomal ends, or telomeres

how can defective protein homeostasis contribute to aging of cells?

loss of protein and accumulation of misfolded proteins can lead to cellular aging

what causes sped up cellular aging?

• genetic abnormalities, causing progressive decline in cellular function and viability

• environmental factors, including diet, social conditions and development of age-related diseases (e.g. atherosclerosis, diabetes and osteoarthritis). They cause progressive accumulation of sub lethal injury over the years at cellular and molecular level.

what is the mechanism of cellular aging

decreased cellular replication over time due to damaged DNA and a reduced ability of cells to divide, along with an accumulation of metabolic and genetic damage

what are telomeres?

short, repeated sequences of DNA present at the ends of chromosomes. they are important for ensuring the complete replication of chromosome ends and for protecting the ends from fusion and degradation

how does telomeres shortening occur?

when somatic cells replicate, a small section of the telomere is not duplicated, becoming progressively shortened as the cycle continues on. it is one of the mechanisms responsible for decreased cellular replication

what is telomerase?

an enzyme that adds nucleotides to the ends of chromosomes (telomeres), helping to maintain their length and protect against DNA shortening during cell division. It is highly expressed in germ cells, present at low levels in stem cells, but largely absent in most somatic cells. By maintaining telomere length, telomerase contributes to cellular longevity and delays some aspects of cellular aging.

what is amyloidosis?

it refers to a group of diseases characterized by the extracellular deposition of fibrillar, misfolded proteinaceous substances called amyloid. Although amyloid deposits share similar morphological features, staining properties, and physical structure, their protein composition can vary depending on the affected organ or underlying disease.

what are the biochemical forms of amyloid?

it consists of three major distinct proteins and more than 20 minors forms.

what are the major forms of amyloids?

1. AL (amyloid light chain protein)

2. AA (amyloid-associated proteins)

3. Aß amyloid

AL (amyloid light chain protein)

fibrils composed of immunoglobin light chains produced by plasma cells and may include either complete light chains, amino-terminal fragments of light chains, or both. They are associated with plasma cell proliferation, such as in multiple myeloma or other monoclonal B-lymphocyte proliferative disorders, and can contribute to amyloid deposition in affected tissues.

AA (amyloid-associated proteins)

fibrils derived from a serum precursor called SAA (serum amyloid-associated protein), which is synthesized by the liver during inflammation. chronic or long-standing inflammation leads to persistently elevated SAA levels, resulting in the formation and deposition of the AA type of amyloid in tissues.

Aß amyloid

derived from a transmembrane glycoprotein called amyloid precursor protein (APP). They are associated with Alzheimer’s disease and are typically deposited in the walls of cerebral blood vessels and in the brain, contributing to the characteristic plaques and neurodegeneration seen in the disease.

what are some minor types of amyloids?

1. ATTR (amyloid transthyretin protein)

2. Aß2m (Amyloid β2– microglobulin)

3. other types including Serum amyloid P component, proteoglycans, and highly sulfated glycosaminoglycans.

ATTR (amyloid transthyretin protein)

normal serum protein that transports thyroxine and retinol. Mutations in the gene encoding TTR can alter its structure, causing the protein to misfold and become resistant to proteolysis. These misfolded proteins aggregate and deposit as amyloid, leading to conditions such as familial amyloid polyneuropathies and senile systemic amyloidosis, which commonly affects the heart in older individuals.

Aß2m (Amyloid β2– microglobulin)

derived from β2-microglobulin, a normal serum protein. It is commonly seen in patients undergoing long-term hemodialysis, where β2-microglobulin accumulates and deposits as amyloid in tissues, leading to dialysis-related amyloidosis.

what is the most common stain used to identify amyloid deposits?

Congo red, which appear pink or red under normal light. When viewed under polarized light, the stained amyloid exhibits apple-green birefringence, a characteristic feature used to confirm the presence of amyloid in tissue samples.