Transcriptional and epigenetic changes in cell senescence and aging

Aging can be defined as the progressive decline of physiological functions over time due to the gradual accumulation of molecular and cellular damage. Even if this inexorable process is physiological, there are some extremely rare genetic diseases, called progeroid syndromes, that constitute a sort of accelerated aging. Among these pathologies, one of the most widely studied is Hutchinson-Gilford progeria syndrome (HGPS), which is primarily caused by the accumulation of a mutated lamin A isoform, known as progerin. However, the precise molecular mechanisms that drive this disease are still not well understood. In this sense, one of the hallmarks of progeroid syndromes is the accumulation of senescent cells. Recent studies suggest that histone levels work as regulators of transcription during physiological aging and senescence, but it is not known whether they have an important role also in progeroid syndromes. The purpose of this work is to analyze changes in the levels of these proteins in the progeroid murine model LmnaG609G/G609G (LAKI). Moreover, as the molecular mechanisms underlying this process in cellular senescence are not completely understood, this work aimed to investigate its possible causes.