Aging as a catabolic malfunction.
Cellular degradative processes, which include lysosomal (autophagic) and proteasomal degradation, as well as catabolism of proteins by cytosolic and mitochondrial proteases, provide for a continuous turnover of cellular components, such as damaged or obsolete biomolecules and organelles. Inherent insufficiency of these degradative processes results in progressive accumulation within long-lived postmitotic cells of biological 'garbage' (waste material), such as various oxidized proteins, functionally effete mitochondria, and lipofuscin (age pigment), an intralysosomal, polymeric, undegradable material. There is increasing evidence that lipofuscin hampers lysosomal degradative capacity, thus promoting the aggravation of accumulated damage at old age. Being rich in redox-active iron, lipofuscin granules also may exacerbate oxidative stress levels in senescent cells. Thus, increasing the efficiency of cellular degradative pathways and preventing involvement of iron in oxidant-induced lysosomal and cellular damage may be potential strategies for anti-aging interventions.
Division of Pathology II, Faculty of Health Sciences, University Hospital, Linköping University, SE-58185 Linköping, Sweden. alete@inr.liu.se
Alexei
A
Terman
Ulf T
UT
Brunk
D000375:Aging / Q000502:physiology; D000818:Animals; D016922:Cellular Senescence / Q000502:physiology*; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D008660:Metabolism / Q000502:physiology*; D013347:Subcellular Fractions / Q000378:metabolism