Send to:

Choose Destination
See comment in PubMed Commons below
Ageing Res Rev. 2007 May;6(1):73-9. Epub 2007 Feb 20.

Premature aging in klotho mutant mice: cause or consequence?

Author information

  • 1Department of Developmental Biology, Harvard School of Dental Medicine, Research and Educational Building, 190 Longwood Avenue, Boston, MA 02115, USA.


Suitable mammalian models for aging with a wide range of age-associated pathology are desirable to study molecular mechanisms of human aging. Recent studies have identified that fibroblast growth factor 23 (Fgf-23) null mice and klotho hypomorphs could generate multiple premature aging-like features, including shortened lifespan, infertility, kyphosis, atherosclerosis, extensive soft tissue calcifications, skin atrophy, muscle wasting, T cell dysregulation, pulmonary emphysema, osteoporosis/osteopenia, abnormal mineral ion metabolism, and impaired vitamin-D homeostasis. The strikingly similar in vivo phenotypes of two separate genetically altered mouse lines implicate that the premature aging-like features may be partly regulated through a common signaling pathway involving both Fgf-23 and klotho; such speculation is experimentally supported by the observation that Fgf-23 requires klotho as a cofactor to exert its functions. Despite about 2000-fold higher serum levels of Fgf-23 in klotho mutants (compared to wild-type animals), these mice show physical, biochemical and morphological features similar to Fgf-23 null mice, but not as Fgf-23 transgenic mice; these observations suggest that widely encountered premature aging-like features in klotho mutant mice are due to the inability of Fgf-23 to exert its bioactivities in absence of klotho. The results of recent studies showing klotho as a cofactor in Fgf-23 signaling consequently explains that the premature aging-like features in klotho-deficient mice is not a primary cause, rather a consequence of lacking Fgf-23 activity. These understandings will help us to redefine the role of klotho as an aging factor.

[PubMed - indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Write to the Help Desk