Comparison of the lateral diffusion coefficient of hepatocyte plasma membrane proteins in three strains of

I Zs -Nagy1, S Tanaka, K Kitani

  • 1National Institute for Longevity Sciences (NILS), 36-3, Gengo, Morioka-cho Obu-shi, 474-8522, Aichi, Japan

Insights

Protein diffusion in liver cells significantly decreases with age in senescence accelerated mice. This finding suggests protein diffusion is a reliable biomarker for aging and survival across various rodent models.

Area of Science:

  • Gerontology
  • Cell Biology
  • Biophysics

Background:

  • Cell membrane protein dynamics are crucial for cellular function and can be affected by aging.
  • Senescence Accelerated Mice (SAM) models are valuable for studying age-related changes.
  • Understanding protein diffusion in hepatocytes provides insights into liver aging.

Purpose of the Study:

  • To investigate the relationship between protein lateral diffusion coefficients (D(p)) in hepatocyte plasma membranes and aging in SAM mice.
  • To evaluate D(p) as a potential biomarker for aging and survival in different SAM strains and housing conditions.
  • To compare age-dependent changes in D(p) between SAM mice and C57BL/6 mice.

Main Methods:

  • Utilized fluorescence recovery after photobleaching (FRAP) to measure D(p) in freshly prepared liver smears.
  • Employed peroxide-induced autofluorescence (PIAF) for D(p) measurements.
  • Studied 115 SAM mice across three strains (SAMR1TA, SAMP6/Ta) and multiple age groups, under specific pathogen-free (SPF) and conventional conditions.

Main Results:

  • A highly significant negative linear correlation between D(p) and age (R=0.975 or higher) was observed in all SAM strains.
  • D(p) values were roughly proportional to the medium life span (MLS) under conventional conditions.
  • Age-dependent decay rates of D(p) showed significant differences between most SAM strain comparisons and with C57BL/6 mice, though not in all SPF comparisons.

Conclusions:

  • Lateral diffusion coefficients of proteins in hepatocyte membranes serve as a robust biomarker of aging and survival in SAM mice.
  • This finding is consistent with previous studies in other inbred and outbred rodent models.
  • D(p) offers a valuable tool for assessing age-related physiological decline in the liver.