Telomere shortening leads to:
Telomeres shorten each cell division because lagging strand synthesis cannot fully replicate chromosome terminus, known as end replication problem. Somatic cells lacking telomerase lose 50 to 200 base pairs per division. When telomere length reaches critical threshold, uncapped ends recognized as double strand breaks trigger DNA damage response activating p53 and p16 pathways, inducing replicative senescence or apoptosis. This divisional counting acts as mitotic clock explaining Hayflick limit. Severe shortening associates with aging syndromes, bone marrow failure, pulmonary fibrosis, whereas cancer cells bypass by reactivating telomerase or alternative lengthening.
Ref: Hayflick Limit and Telomere Attrition Hypothesis; Alberts et al., Molecular Biology of the Cell, Chapter 20: Telomere Shortening Causes Aging