Open AccessAt the crossroads of longevity and metabolism: the metabolic syndrome and lifespan determinant pathways
Author(s) -
Fadini Gian Paolo,
Ceolotto Giulio,
Pagnin Elisa,
de Kreutzenberg Saula,
Avogaro Angelo
Publication year - 2011
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/j.1474-9726.2010.00642.x
Subject(s) - longevity , biology , regulator , transcription factor , nutrient sensing , mechanism (biology) , population , metabolic pathway , bioinformatics , gene , genetics , signal transduction , medicine , philosophy , environmental health , epistemology
Summary The metabolic syndrome is becoming increasingly prevalent in the general population and carries significant incremental morbidity and mortality. It is associated with multi‐organ involvement and increased all‐cause mortality, resembling a precocious aging process. The mechanisms that account for this phenomenon are incompletely known, but it is becoming clear that longevity genes might be involved. Experiments with overactivation or disruption of key lifespan determinant pathways, such as silent information regulator (SIR)T1, p66Shc, and mammalian target of rapamycin (TOR), lead to development of features of the metabolic syndrome in mice. These genes integrate longevity pathways and metabolic signals in a complex interplay in which lifespan appears to be strictly dependent on substrate and energy bioavailability. Herein, we describe the roles and possible interconnections of selected lifespan determinant molecular networks in the development of the metabolic syndrome and its complications, describing initial available data in humans. Additional pathways are involved in linking nutrient availability and longevity, certainly including insulin and Insulin‐like Growth Factor‐1 (IGF‐1) signaling, as well as FOXO transcription factors. The model described in this viewpoint article is therefore likely to be an oversimplification. Nevertheless, it represents one starting platform for understanding cell biology of lifespan in relation to the metabolic syndrome.