The concept of telomeric non-reciprocal recombination (TENOR) applied to human fibroblasts grown in serial cultures: concordance with genealogical data

Abstract

Since the discovery of the limited life span of human fibroblasts some 50 years ago, many genealogical studies have been undertaken to describe growth kinetics of fibroblasts in serial cultures by their individual division behavior. It is now accepted that proliferation capacities of human fibroblasts strongly depend on their telomere lengths and integrity. Telomeres shorten with each replication round, and there is a direct correlation between cell division capacity and telomere lengths; that is, the consumption of disposable telomeric DNA repeats during cell divisions progresses until critically short telomeres determining the replicative senescence of the cells are present. Recently, we have suggested that telomeres in fibroblasts can also become elongated during DNA replication by telomeric non-reciprocal recombination (TENOR). Here we discuss genealogical data collected over the last decades as well as more recent findings on the telomere-driven replicative senescence process, and we summarize both to give an integrated picture.