Progeroid syndromes (PSs) constitute a group of disorders characterized by clinical features mimicking physiological aging at an early age. In some of these syndromes,
biological hallmarks of aging are also present, whereas in others, a link with physiological aging, if any, remains to be elucidated. These syndromes are clinically and genetically heterogeneous and most of them, including
Werner syndrome and Hutchinson-Gilford
progeria, are known as 'segmental aging syndromes', as they do not feature all aspects usually associated to physiological aging. However, all the characterized PSs enter in the field of rare monogenic disorders and several causative genes have been identified. These can be separated in subcategories corresponding to (i) genes encoding DNA repair factors, in particular,
DNA helicases, and (ii) genes affecting the structure or post-translational maturation of
lamin A, a major nuclear component. In addition, several animal models featuring
premature aging have abnormal mitochondrial function or signal transduction between membrane
receptors, nuclear regulatory
proteins and mitochondria: no human pathological counterpart of these alterations has been found to date. In recent years, identification of mutations and their functional characterization have helped to unravel the cellular processes associated to segmental PSs. Recently, several studies allowed to establish a functional link between DNA repair and A-type
lamins-associated syndromes, evidencing a relation between these syndromes, physiological aging and
cancer. Here, we review recent data on molecular and cellular bases of PSs and discuss the mechanisms involved, with a special emphasis on
lamin A-associated
progeria and related disorders, for which therapeutic approaches have started to be developed.