Age-Related Changes in the Lipofuscin Accumulation of Brain and Heart

Abstract

Lipofuscin is the end-product of intracellular lipid peroxidation and the accumulation results from the cellular metabolism during aging (life stage). We suggested that the accumulation of cardiac lipofuscin was dependent on the specific metabolic rate of mammals. Slower rate of cardiac lipofuscin accumulation (against absolute lifespan) was observed in the animals of larger body size. The rate of cardiac lipofuscin accumulation was correlated with the specific metabolic rate, and inversely correlated with the brain weight of mammals. The first appearance of lipofuscin granules was 8 weeks of age in the hippocampus and in the thalamus. In the case of cerebral cortex (laminae III), lipofuscin granules were first found at 3-month-old rats. The rate of lipofuscin accumulation was the highest in the hippocampus (y = 0.286x -0.099, r = 0.963) among the three regions examined. In the case of cerebral cortex and thalamus, the slower rate of lipofuscin accumulation was observed (y= 0.072x – 0.14, r = 0.797 for cerebral cortex; y=0.067X – 0.14, r = 0.953 for thalamus). It is noticed that the most abundant accumulation and the highest rate of lipofuscin accumulation are the hippocampus. Even the hippocampus, the rate and the magnitude of lipofuscin accumulation was low as compared with cardiac muscles. From these results, it is suggested that brains have better protective system against oxidative stress than other organs do.

Defective recruitment of motor proteins to autophagic compartments contributes to autophagic failure in aging

“…Alterations in the last step of autophagy—the degradation of cargo in the lysosomal lumen (Hayasaka, 1989; Ivy, Schottler, Wenzel, Baudry & Lynch, 1984; Nakano, Oenzil, Mizuno & Gotoh, 1995; Tauchi, Hananouchi & Sato, 1980)—and reduced autophagosome/lysosome fusion have both shown to contribute to autophagic failure in the old liver (Terman, 1995). Although the extensive changes in the lipid composition of intracellular membranes reported in old cells (Kitani, 1999; Rottem & Greenberg, 1975) lead to the proposal that reduced vesicle fusogenicity was behind autophagosome maturation, our studies with isolated autophagosomes and lysosomes reveal that fusion between these two compartments is actually enhanced and not reduced.…”

The use of honeybees reared in a thermostatic chamber for aging studies

“…The accumulation of lipofuscin granules has also been extensively used to evaluate cellular senescence in many cell types such as the skin, dermis, and muscle of zebrafish (D. rerio) (Kishi et al 2003), the brain and heart of rats (Nakano et al 1995), the neonatal cardiac myocytes of rats (Brunk and Terman 2002), the liver and caudal peduncle of N. furzeri (Genade et al 2005), and the gills of N. rachovii (Hsu et al 2008). SA-β-Gal and lipofuscin granules have been also used to determine the aging of trophocytes and fat cells in workers reared in the field hive (Hsieh and Fig.…”

“…Lipofuscin cannot be degraded by lysosomal hydrolases or exocytosed. Accumulation of lipofuscin granules has been reported to increase with age (Nakano et al 1995;Brunk and Terman 2002;Kishi et al 2003;Genade et al 2005;Hsu et al 2008;Hsieh and Hsu 2011). Thus, accumulation of both SA-β-Gal and lipofuscin are considered reliable indices of advancing age.…”

“…These age-related molecules include senescence-associated β-galactosidase (SA-β-Gal) (Dimri et al 1995), lipofuscin granules (Nakano et al 1995), lipid peroxidation (Draper and Hadley 1990;Almeida et al 1998), and protein oxidation (Welis-Knecht et al 1993). SA-β-Gal is a eukaryotic hydrolase that is localized in the lysosome (Kurz et al 2000), and SA-β-Gal expression increases with age (Dimri et al 1995;Kishi et al 2003;Genade et al 2005;Hsu et al 2008;Hsieh and Hsu 2011).…”

Autophagy, organelles and ageing

“…Of great interest is the fact that postmitotic cells of short-lived animals accumulate lipofuscin rapidly, while the reverse holds true for long-lived animals [81]. This finding suggests a relationship between lipofuscin accumulation, function of the lysosomal compartment and cell survival.…”