AGING: The plot really thickens

From: Robert J. Bradbury (
Date: Wed Jan 23 2002 - 10:15:18 MST

As I predicted a number of years ago we are starting to see a significant
increase in the comprehension of aging related disorders.

I was previously unaware of the "klotho" mice that show accelerated
aging similar to that seen in humans with heart disease.

The Boston Globe is reporting that certain variants of the klotho gene
appear to be causing humans to die before they hit age 65:

The PNAS abstract is here:
The prerelease paper here:

(I can't get to the full paper because I don't have a PNAS subscription).

But doing a PubMed search turns up ~49 articles on klotho.

Interestingly enough, klotho deficient mice lack white adipose tissue:

and white adipose tissue functions as an endocrine organ, being responsible
for the production of leptin and resistin, here:

Klotho mice also show an inability to produce insulin:

This suggests that a tight control of energy homeostasis, involving
insulin, leptin and resistin are essential for regulating blood levels
of glucose and triglycerides. Failure to control these levels seems
to result in accelerated aging even though the temperature of the
klotho mice is lower.

Interestingly, one can apparently modulate the effects of a lack of klotho
by changing dietary levels of phosphorus and zinc.

I can't get to the paper involved but the abstract suggests that the mice
return to normal on *reduced* phosphorus intake. That sounds like an
interesting strategy as reduced phosphorus would probably slow down
your entire energy production capability (less phosphorus means less ATP).

The abstract mentions a zinc tie-in but doesn't provide any data. But
the white adipose tissue is also supposed to produce and secrete
metallothionein which can function as an antioxidant in response to stress.
A lack of WAT would diminish the availability of systemic metallothionein
which could be offset by production elsewhere under the stimulation of

Thus there is a very nice tie-in for all of this with both the free radical
theory of aging and the glycosylation theory of aging.


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