Effects of aging and calorie restriction of Fischer 344 rats on hepatocellular response to proliferative signals.

Abstract:

:It is well established that the proliferative potential of the liver declines with aging. Epidermal growth factor (EGF)-stimulated DNA synthesis is reduced in hepatocytes from aged rats relative to young rats, and this reduction correlates with diminished activation of the extracellular signal-regulated kinase (ERK) pathway and lower phosphorylation of the EGF receptor on residue Y1173. Calorie restriction (CR) can increase rodent life span and retard many age-associated declines in physiologic function, but its influence on cell proliferation is unknown. Here, we investigated the effects of long-term CR on proliferation of hepatocytes derived from young and aged rats following in vitro stimulation with either low-dose hydrogen peroxide or EGF. CR reduced the proliferative response of hepatocytes derived from young hosts, but long-term CR was associated with enhanced proliferation in aged cells relative to that of ad libitum (AL)-fed animals. ERK activation mirrored the effects of CR on proliferation, in that young CR cells exhibited lower ERK activation than young AL cells, but old CR cells showed higher ERK activation than old AL cells. Finally, a decline in EGF receptor phosphorylation on Y1173, which normally occurs with aging, was absent in cells of old hosts maintained on long-term CR, supporting the view that alterations in this early signaling event underlie the age-related decline in proliferative potential in rat hepatocytes.

journal_name

Exp Gerontol

journal_title

Experimental gerontology

authors

Ikeyama S,Kokkonen G,Martindale JL,Wang XT,Gorospe M,Holbrook NJ

doi

10.1016/s0531-5565(02)00239-5

keywords:

subject

Has Abstract

pub_date

2003-04-01 00:00:00

pages

431-9

issue

4

eissn

0531-5565

issn

1873-6815

pii

S0531556502002395

journal_volume

38

pub_type

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