TRPV1 pain receptors regulate longevity and metabolism by neuropeptide signaling.

The sensation of pain is associated with increased mortality, but it is unknown whether pain perception can directly affect aging. We find that mice lacking TRPV1 pain receptors are long-lived, displaying a youthful metabolic profile at old age. Loss of TRPV1 inactivates a calcium-signaling cascade that ends in the nuclear exclusion of the CREB-regulated transcriptional coactivator CRTC1 within pain sensory neurons originating from the spinal cord.

Brain IGF-1 receptors control mammalian growth and lifespan through a neuroendocrine mechanism.

Mutations that decrease insulin-like growth factor (IGF) and growth hormone signaling limit body size and prolong lifespan in mice. In vertebrates, these somatotropic hormones are controlled by the neuroendocrine brain. Hormone-like regulations discovered in nematodes and flies suggest that IGF signals in the nervous system can determine lifespan, but it is unknown whether this applies to higher organisms.

Early postnatal nutrition determines somatotropic function in mice.

Increasing evidence suggests a developmental origin for a number of human diseases, notably after intrauterine or postnatal nutrient deprivation. Nutritional changes readily translate into alterations of somatic growth. However, whereas intrauterine growth retardation often shows postnatal catch-up growth, recovery from food restriction immediately after birth is limited.

[Ageing, genetics and the somatotropic axis].

Research on ageing made a big leap forward when genes regulating lifespan were discovered about a decade ago. First isolated by screening the genome of the nematode Caenorhabditis elegans, most of these genes belong to an essential signalling pathway that is highly conserved during animal evolution. Orthologous genes in vertebrate species are the families of genes coding for insulin, insulin-like growth factors (IGF) and related proteins.

IGF-1 signaling and aging.

We briefly compare calorie restriction, GHRH-R and Pit-1 mutants with knockout phenotypes of GH receptor, IGF-1 receptor and p66Shc, to make some general conclusions. Growth, fertility and longevity phenotypes may dissociate in some of these mutants, and we try to interpret this. Follows a short discussion on the importance of genetic background for aging studies in mice.