Martin Adamo, PhD
Adjunct Professor (Retired, UT Health San Antonio)
BS, University of Houston, 1979
MS, University of Houston, 1982
PhD, University of Houston, 1986
Post Doctoral: Diabetes Branch, NIDDK, NIH, 1986-1992
Our laboratory studies insulin-like growth factor-I (IGF-I) synthesis and action throughout the life span. IGF-I is a 70 amino acid peptide synthesized primarily by the liver, which secretes this growth factor into the circulation. Most extra-hepatic tissues also synthesize IGF-I. Thus, IGF-I acts as both a circulating endocrine and autocrine/paracrine growth factor. IGF-I acts by binding to a heterotetrameric receptor with inherent tyrosine kinase activity.
IGF-I binding stimulates the tyrosine kinase activity of the receptor resulting in a sequence of biochemical events that cause the activation of two major signaling kinases. One of these is the lipid kinase phosphatidylinositol 3-kinase (PI3K) and the other is the extracellular signal regulated kinase (ERK). Products of PI3K lead to the activation of a number of downstream kinases, most notably Akt/protein kinase B. ERK phosphorylates a variety of substrates. Collectively, these actions lead to increased cellular proliferation, survival, anabolism, and differentiated function.
IGF-I synthesis and secretion is highly regulated consistent with its important role in stimulating normal growth and metabolism, and mediating tissue maintenance and regeneration after damage. However, IGF-I also stimulates pathological growth processes such as fibrosis and cancer. Given these pleiotropic effects of IGF-I, it is not surprising that IGF-I has been implicated in the aging process. Reduction in IGF-I action leads to age-associated impairment of tissue function such as osteo- and sarco-penia. On the other hand, reductions in IGF-I action may actually reduce biological aging by decreasing cancer progression and by decreasing fibrotic and inflammatory pathways.
We utilize in vitro cell culture and in vivo animal models with manipulations of IGF-I and components of the IGF-I signaling pathway to determine the effects of IGF-I on the growth, differentiation, survival and metabolism of specific tissues and whole animals. For example, we are elucidating signaling pathways by which IGF-I mediates muscle survival during oxidative stress in vitro and in vivo, and how IGF-I and factors that regulate IGF-I mediate allocation of precursor cells into osteoblastic, myogenic and adipogenic lineages. We are also determining the effects of IGF-I levels and signaling on stress response, metabolism, and life span in intact experimental animals.
- Does reduced IGF-1R signaling in Igf1r+/- mice alter aging?
Bokov AF, Garg N, Ikeno Y, Thakur S, Musi N, DeFronzo RA, Zhang N, Erickson RC, Gelfond J, Hubbard GB, Adamo ML, Richardson A
PLoS One: 2011-11-23; 6(11); e26891 Epub: 2011-11-23.
- Increased serum IGF-1 levels protect the musculoskeletal system but are associated with elevated oxidative stress markers and increased mortality independent of tissue igf1 gene expression.
Elis S, Wu Y, Courtland HW, Sun H, Rosen CJ, Adamo ML, Yakar S
Aging Cell: 2011-06-01; 10(3); 547-50 Epub: 2011-03-22.