While the effect of insulin sensitivity on lifespan is complex – some insulin-resistant mice, such as mice lacking IRS1, are long lived (Taguchi et al., 2007; Selman et al., 2008, 2011) – many long-lived mouse models have increased insulin sensitivity, and diet-induced insulin resistance shortens mammalian lifespan (Kenyon, 2001).
The role of HSD-1 in lifespan control is complex.
Furthermore, human lifespan is a complex trait which is assumed to be determined by many genes with small individual effects 17, although the polygenic architecture still needs to be characterized 18, 19.
Although the genetic modulation of lifespan is more complex and less efficient in mammals, the advance in knowledge about the interaction of the age-related genes and the environment is starting to be used to extend the lifespan of these animals (de Magalhaes et al., 2012).
In our dOpa1+/− Drosophila model, the most severely damaged electron transport chain unit is complex II, suggesting that complex II is an important determinant of Drosophila lifespan.
Moreover, while natural lifespan is likely a complex trait controlled by many genes with small effect sizes, extreme longevity may be determined by fewer genes of stronger effect [22], [23], and may therefore be amenable to linkage analysis.
Lifespan is determined by a complex interplay between environmental and genetic factors.
Instead, the data are consistent with the idea that yeast chronological lifespan is defined by a complex combination of numerous factors, and is a highly multigenic process regulated at the transcriptional level.
Accordingly, mouse lifespan is influenced by MHC (major histocompatibility complex) genotype.
The canonical target of rapamycin, and the one thought to account for its effects on lifespan, is the mammalian/mechanistic target of rapamycin, complex 1 (mTORC1).
Whether complex mental activity across the lifespan is related to hippocampal volume in late life, or the rate of hippocampal atrophy over time, has yet to be examined.
