Integrity matters: Linking nuclear architecture to lifespan
- Department of Cell Biology, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205
Daily choices, of food, activity level, sun exposure, can positively influence the chance of living a long healthy life. Through these choices, we apparently influence some of the same biochemical and genetic pathways that regulate lifespan in lower eukaryotes. For example, conserved genes that regulate insulin/IGF-1 signaling and oxidative stress responses control longevity in Caenorhabditis elegans, Drosophila, and mice (1). The genetic control of lifespan is conserved in metazoan evolution, as first shown by classic studies with the nematode C. elegans (2). Lifespan and aging in mammals also may be influenced by the efficiency of DNA repair and replacement of damaged tissue by stem cells (1). Because aging is a complex phenomenon, and because lifespan can be shortened by many extraneous factors (e.g., toxins, bad genes, bad driving), the litmus test for truly aging-relevant pathways has been whether mutations in these pathways can extend lifespan. In contrast, lifespan is reduced in Hutchinson–Gilford progeria syndrome (HGPS) and other human “accelerated aging” (progeria) syndromes, leading to ongoing debate as to whether these syndromes can provide insight into the mechanisms of normal aging (1, 3). New findings in C. elegans, the classic model organism for aging, now reveal a fundamental link between lifespan and the nucleus. In a key breakthrough, Haithcock et al. (4), in a recent issue of PNAS, showed that normal aging in C. elegans involves progressive stochastic (cell-by-cell) deterioration of nuclear …
