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How does suppression of IGF-1 signaling by DNA damage affect aging and longevity?

Mechanisms of ageing and development (2008-04-01)
George Hinkal, Lawrence A Donehower
ABSTRACT

Long-lived animals have evolved a robust set of defenses to maintain genomic integrity over their entire lifespan. The DNA damage response and DNA repair pathways are critical pillars of organismal defenses, minimizing somatic mutations in both post-mitotic and mitotic cells. These genomic maintenance systems not only prevent the premature emergence of cancers but may also maintain normal tissue function and organismal longevity. Genetic defects in a number of DNA repair and DNA damage response genes often leads to a dramatic increase in cancer incidence; in other cases, premature aging or progeroid syndromes may be induced. In this review, we discuss two recent reports of two nucleotide excision repair-deficient models that exhibit dramatic premature aging and shortened longevity. The DNA repair defects were also associated with a significant inhibition of the growth hormone/insulin-like growth factor 1 (GH/IGF-1) axis, an endocrine signaling pathway shown to influence aging and longevity in both vertebrates and invertebrates. Potential mechanisms of how DNA damage might affect IGF-1 signaling and aging are discussed, with a particular emphasis on the role of such signaling alterations in the adult tissue stem cell compartments.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
MISSION® shRNA Human Gene Family Set, Lentiviral Particles, DNA Repair Pathway
Sigma-Aldrich
MISSION® shRNA Human Gene Family Set, DNA, DNA Repair Pathway
Sigma-Aldrich
MISSION® shRNA Human Gene Family Set, Bacterial Glycerol Stock, DNA Repair Pathway