COMMENTARY
Impact of reduced insulin-like growth factor-1/insulin signaling on
aging in mammals: novel findings
Andrzej BartkeDepartments of Internal Medicine and Physiology, School
of Medicine, Southern Illinois University, Springfield, IL 62794-9628,
USA
Correspondence
Andrzej Bartke, PhD, Department of Medicine, Division of Geriatric
Research, School of Medicine, Southern Illinois University, PO Box
19628, Springfield, IL 62794-9628, USA. Tel.: 217/545-7962; fax:
217/545-8006; e-mail: abar... at (no spam) siumed.edu
Key words: IGF-1; insulin; lifespan; longevity; somatotrophic axis.
Summary

Growth hormone deficiency or resistance resulting from spontaneous or
experimentally produced mutations in laboratory mice delay aging and
increase lifespan. Alterations in insulin-like growth factor-1 (IGF-1)
and insulin signaling emerged as likely mechanisms linking growth
hormone and aging, and increased longevity was reported in mice with
selective deletion of IGF-1 receptor in all tissues or insulin
receptor in fat. Recent studies in mice with reduced IGF-1 levels or
deletion of pregnancy-associated plasma protein-A, a protease that
cleaves one of the IGF-1 binding proteins, strongly support the role
of IGF-1 in the control of longevity. Reports of increased lifespan in
mice with deletion of insulin receptor substrate (IRS) 1, reduced
expression of IRS2, or selective deletion of IRS2 in the brain
specifically implicate the IRS-PI3K-Akt-Foxo signaling pathway (which
is shared by IGF-1 and insulin) in the control of aging. These
important novel findings also strengthen the evidence for evolutionary
conservation of mechanisms regulating lifespan in worms, insects and
mammals