These investigators are studying additional mechanisms (other than insulin/IGF-1) for the metabolic decline with aging. Special efforts are focused on furthering the recent findings of the hypothalamus as regulator not only of food intake and whole body energy balance, but also of glucose metabolism and inflammation. Researchers are studying the central control of food intake (Schwartz, Chua)40,41, and inflammation (Cai)42 with aging, and have collaboratively developed tools to probe the hypothalamus in chronic, unstressed, awake rodents. Increased fat mass and changes in body fat distribution with aging also cause 43 glucose intolerance and systemic inflammation, presumably due to production of pro-inflammatory ‘adipokines’ from fat tissue. Several other investigators have developed tools to study these changes and the biology of adipose tissue and its role in inflammation (Barzilai, Hawkins, Pessin, Bastie)44-46, and cancer (Augenlicht)47.
- Blouet, C., Jo, Y. H., Li, X. & Schwartz, G. J. Mediobasal hypothalamic leucine sensing regulates food intake through activation of a hypothalamus-brainstem circuit. J Neurosci 29, 26:8302-8311, doi:29/26/8302 [pii]10.1523/JNEUROSCI.1668-09.2009 (2009).
- Kitamura, T., Feng, Y., Kitamura, Y. I., Chua, S. C., Jr., Xu, A. W., Barsh, G. S. et al. Forkhead protein FoxO1 mediates Agrp-dependent effects of leptin on food intake. Nat Med 12, 5:534-540, doi:nm1392 [pii]10.1038/nm1392 (2006).
- Cai, D., Yuan, M., Frantz, D. F., Melendez, P. A., Hansen, L., Lee, J. et al. Local and systemic insulin resistance resulting from hepatic activation of IKK-beta and NF-kappaB. Nat Med 11, 2:183-190, doi:nm1166 [pii]10.1038/nm1166 (2005).
- Muzumdar, R., Allison, D. B., Huffman, D. M., Ma, X., Atzmon, G., Einstein, F. H. et al. Visceral adipose tissue modulates mammalian longevity. Aging Cell 7, 3:438-440, doi:ACE391 [pii]10.1111/j.1474-9726.2008.00391.x (2008).
- Bastie, C. C., Zong, H., Xu, J., Busa, B., Judex, S., Kurland, I. J. et al. Integrative metabolic regulation of peripheral tissue fatty acid oxidation by the SRC kinase family member Fyn. Cell Metab 5371-381 (2007).
- Lin, Y., Berg, A. H., Iyengar, P., Lam, T. K., Giacca, A., Combs, T. P. et al. The hyperglycemia-induced inflammatory response in adipocytes: the role of reactive oxygen species. J Biol Chem 280, 6:4617-4626, doi:M411863200 [pii]10.1074/jbc.M411863200 (2005).
- Rudin, E. & Barzilai, N. Inflammatory peptides derived from adipose tissue. Immun Ageing 2, 1:1, doi:1742-4933-2-1 [pii]10.1186/1742-4933-2-1 (2005).
- Newmark, H. L., Yang, K., Kurihara, N., Fan, K., Augenlicht, L. H. & Lipkin, M. Western-style diet-induced colonic tumors and their modulation by calcium and vitamin D in C57Bl/6 mice: a preclinical model for human sporadic colon cancer. Carcinogenesis 30, 1:88-92, doi:bgn229 [pii]10.1093/carcin/bgn229 (2009).