Page 45 - Concise Pathology for Exam Preparation ( PDFDrive )

30 SECTION I General Pathology

Morphologic Alterations due to Cell Ageing

• Irregular and abnormal location of nuclei
• Pleomorphic and vacuolated mitochondria
• Dilated and distorted endoplasmic reticulum
• Distorted Golgi apparatus

Theories of Cell Ageing
Cell ageing is considered to be multifactorial in origin. Factors influencing cell ageing
include:
1. Endogenous molecular programme of cellular senescence:
(a) Normally, DNA damage is repaired by DNA repair enzymes.
(b) Accumulation of DNA damage due to defective DNA repair mechanisms induces
ageing.
(c) Also, contribution from activation of senescence-inducing apoptotic genes (on
chromosomes 1 and 4) and induction of growth inhibitors.
(d) Telomeres are critical for stabilization of terminal portion of chromosomes and
anchoring them to the nuclear matrix. De novo synthesis of telomeres is regulated
by an enzyme called telomerase. During somatic cell replication, a small segment of
the telomere is not duplicated leading to telomere shortening and loss of DNA, in-
ducing cellular ageing.
(e) Telomerase repairs the shortened tips of chromosomes and maintains their length.
(f) Repetitive mitoses (60–70 times) telomeres lost cell ageing.
(g) Telomerase activity upregulated telomere length maintained
avoids cell ageing.
2. Exogenous influences (Flowchart 1.15):

Free radical injury

Covalent modification of intracellular and extracellular proteins, lipids and nucleic acids

Declining function of proteasomes (proteolytic machine that eliminates abnormal or unwanted intracellular
proteins)

Accumulation of damaged cellular organelles

Cell ageing
FLOWCHART 1.15. Exogenous influences in cellular ageing.

Q. What are heat shock proteins (HSPs)?
Ans. HSPs were so labelled because they were found in fruit fly larvae after slight elevation
of temperature. They are essential to cell survival in species subjected to injury. There are
two families of HSP—HSP 70 and HSP 60.
• HSP are involved in intracellular protein folding and translocation as well as targeting
of proteins to their final destination. They are therefore also called chaperones or chap-
eronins.
• Their levels increase in stress.

Ubiquitin

• It is a small HSP critical to protein degradation (proteins degraded in cellular incinera-
tors called ‘proteasomes’ when denatured beyond repair)
• Ubiquitin is universally or ubiquitously present in cells

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