Question

Provide two explanations for how telomeres/telomerase modulate the aging process and discuss a disease that involves premature aging. Provide all citations (in-text as well).

Answer 1

Telomeres are the specialized repetitive DNA sequences at the ends of the linear chromosomes, and associated proteins, that serve to maintain the integrity of the chromosomes. Telomerase is a ribonucleoprotein DNA polymerase complex that maintains telomere length. Telomerase resembles reverse transcriptase (TERT) enzymes that synthesize DNA using an RNA template and also catalytic RNA (TERC). In the absence of telomerase activity telomeres progressively shorten and lead to ageing. In most normal human somatic cells Telomerase activity is absent due of the lack of expression of TERT. Without telomerase, telomere shortening stop the growth of cells, either:-

1) Due to senescence, in cells with intact cell cycle checkpoints which blocks cell cycle at G1.

2) due to crisis in cells with inactivated checkpoints that is telomeric end-to-end fusions cause chromosome breakage and mitotic catastrophe.

Low socio-economic status (SES) , may also contribute to the shortening of telomeres of WBC, which lead to ageing in human. stress impacts health by modulating the rate of cellular aging. (Cherkas LF, Aviv A, Valdes AM, Hunkin JL, Gardner JP, Surdulescu GL, Kimura M, Spector TD,Aging Cell. 2006 Oct; 5(5):361-5)

In peripheral blood mononuclear cells from healthy premenopausal women it is demonstrated that  psychological stresses are significantly associated with higher oxidative stress, lower telomerase activity, and shorter telomere length, which are known determinants of cell senescence and longevity in cells. ( Epel ES, Blackburn EH, Lin J, Dhabhar FS, Adler NE, Morrow JD, Cawthon RM, Proc Natl Acad Sci U S A. 2004 Dec 7; 101(49):17312-5.)