Endocrine and Metabolic Signaling in Promoting Healthy Aging
Meng Wang
Department of Molecular Biology, Massachusetts General Hospital
Department of Genetics, Harvard Medical School
Boston, Massachusetts 02114, USA
Aging is a complex process of intrinsic deterioration, and a major risk factor for cancer,
metabolic syndromes, cardiovascular disorders and neurodegenerative diseases.
Adipose tissue and the reproductive system are essential endocrine organs, releasing
adipokines, lipokines and steroid hormones to coordinate organism physiology.
During aging, degenerative changes in these key endocrine organs are associated
with various age-related diseases such as type II diabetes, central obesity, cancer,
and cardiovascular disorders. We have discovered that germline stem cell
proliferation exerts active effects on fat metabolism by modulating lipases and lipid
chaperones in Caenorhabditis elegans. Both lipases and lipid chaperones play vital
roles in the regulation of somatic maintenance and longevity. Via a full genome RNA
interference (RNAi) screen, we have identified novel factors that regulate
age-associated reproductive senescence, including signaling molecules, metabolic
genes, transcription factors and secreting hormones. Many of these candidate genes
play critical roles in the regulation of stress responses, fat metabolism, and longevity.
These results have revealed the endocrine crosstalk between germline stem cells and
fat storage tissue, the novel role of lipid metabolism in the regulation of longevity and
the molecular mechanisms underlying organ aging. We believe these studies will
advance our knowledge on the fundamental mechanisms of aging, and also provide
promising pharmaceutical targets to improve healthy aging