Cellular senescence is a form of irreversible arrest initially characterized as the state attained at the end of a cell's replicative lifespan. Subsequently, senescence has been linked with organismal aging and is suggested as a key driver of the aging process . However, senescence can also be induced prematurely in response to active oncogenes and DNA damage. This oncogene-induced senescence (OIS) is a potent tumor suppressive mechanism in vivo, preventing the aberrant proliferation of initiated cells; and for a tumor to form, the cell must overcome senescence-imposed barriers. In addition, the reactivation of senescence within the tumor microenvironment, or in response to chemotherapy, can aid in the arrest of tumor growth and facilitate tumor clearance, highlighting its promise as a therapeutic mechanism . In brief, senescence represents a critical focal point between cancer and aging, requiring that a precise balance be maintained to avoid predisposition to either process. Consequently, understanding the molecular regulation of senescence is crucial to cancer treatment and anti-aging therapies.
Regardless of the initiating force, senescence is identified by hallmark features including the activation of tumor suppressor networks and extensive epigenetic changes. The latter include a major redistribution of heterochromatin into senescence-associated heterochromatic foci (SAHFs), which contribute to gene repression and the irreversibility of the arrested state .
Recently, De Cecco et al.  uncovered another aspect of the complex biology of senescence. Using a technique known as “formaldehyde-assisted isolation of regulatory elements” (FAIRE), to profile genome-wide chromatin changes in replicative senescent human diploid fibroblasts, they discovered that aged cells in culture display a striking activation of retrotransposable elements (RTEs), including retrotransposons and satellite repeats. In their “Hypothesis” article in this issue , they discuss the implications for the reactivation of RTEs in the context of senescence and aging, and hypothesize how manipulation of transposable element activation in the aged state may represent a novel strategy to alleviate some aspects of aging.
Transposable elements are mobile pieces of DNA that can randomly insert into the genome. While this random insertion is thought to favor evolutionary advance, the uncontrolled activation of RTEs can lead to DNA damage and genomic instability. As such, cells employ elaborate mechanisms to maintain their repression by heterochromatinization. As discussed in their article, the authors propose that a loosening of the control mechanisms in senescent cells might lead to the aberrant activation of transposable elements.
However, given that RTE activation in senescent cells was identified after long-term culture, it will be interesting to see whether similar RTE mobilization is seen in aged tissue. Furthermore, it is likely that transposable element activation is a consequence of senescence-associated alterations in the regulatory processes, rather than a driving force per se. Therefore, while inhibition of their mobilization might not fully prevent senescence induction, such treatments may have pronounced effects on tumor initiation. Indeed, if similar activation of RTEs is observed in OIS, they might silence tumor suppressor genes, or generate genomic instability, thereby favoring tumor initiation or recurrence after therapy. Undeniably, the development of improved tools for next-generation sequencing will allow for the detailed study of the timing and sequence of these changes, and the identification of cell-type specific patterns in vivo. Ultimately, however, the notion that transposable elements undergo mobilization in senescent cells establishes yet another link between senescence, cancer and aging that merits clearer understanding.