Mitochondrial turnover and aging of long-lived postmitotic cells: the mitochondrial-lysosomal axis theory of aging.

Department of Clinical Pathology and Cytology, Karolinska University Hospital, Huddinge, Stockholm, Sweden.
Antioxidants & Redox Signaling (Impact Factor: 7.67). 09/2009; 12(4):503-35. DOI: 10.1089/ars.2009.2598
Source: PubMed

ABSTRACT It is now generally accepted that aging and eventual death of multicellular organisms is to a large extent related to macromolecular damage by mitochondrially produced reactive oxygen species, mostly affecting long-lived postmitotic cells, such as neurons and cardiac myocytes. These cells are rarely or not at all replaced during life and can be as old as the whole organism. The inherent inability of autophagy and other cellular-degradation mechanisms to remove damaged structures completely results in the progressive accumulation of garbage, including cytosolic protein aggregates, defective mitochondria, and lipofuscin, an intralysosomal indigestible material. In this review, we stress the importance of crosstalk between mitochondria and lysosomes in aging. The slow accumulation of lipofuscin within lysosomes seems to depress autophagy, resulting in reduced turnover of effective mitochondria. The latter not only are functionally deficient but also produce increased amounts of reactive oxygen species, prompting lipofuscinogenesis. Moreover, defective and enlarged mitochondria are poorly autophagocytosed and constitute a growing population of badly functioning organelles that do not fuse and exchange their contents with normal mitochondria. The progress of these changes seems to result in enhanced oxidative stress, decreased ATP production, and collapse of the cellular catabolic machinery, which eventually is incompatible with survival.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Curcuminoids (curcumin, demethoxycurcumin, bis-demethoxycurcumin) are lipophilic polyphenols thought to be effective in the prevention and treatment of neurodegenerative disorders, of which mitochondrial dysfunction is a prominent feature. In particular, older people may thus benefit from increasing their curcuminoid intake. However until now, it is not investigated if there exist age differences in the bioavailability of curcuminoids and therefore, it is unclear if curcumin doses have to be adjusted to age. Thus, we explored if the tissue concentrations and biological activities of curcuminoids are affected by age.
    06/2015; 1:3-8. DOI:10.1016/j.nfs.2015.03.002
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Decline in human muscle mass and strength (sarcopenia) is one of the principal hallmarks of the aging process. Regular physical exercise and training programs are certain powerful stimuli to attenuate the physiological skeletal muscle alterations occurring during aging and contribute to promote health and well-being. Although the series of events that led to these muscle adaptations are poorly understood, the mechanisms that regulate these processes involve the “quality” of skeletal muscle mitochondria. Aerobic/endurance exercise helps to maintain and improve cardiovascular fitness and respiratory function, whereas strength/resistance-exercise programs increase muscle strength, power development, and function. Due to the different effect of both exercises in improving mitochondrial content and quality, in terms of biogenesis, dynamics, turnover, and genotype, combined physical activity programs should be individually prescribed to maximize the antiaging effects of exercise.
    Oxidative medicine and cellular longevity 01/2015; 2015:1-15. DOI:10.1155/2015/917085 · 3.36 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: One of the consequences of oxygen metabolism is the production of reactive oxygen species (ROS) which in a situation of imbalance with antioxidants can damage several biomolecules, compromise cell function and even lead to cellular death. The particularities of the sperm cell make it particularly vulnerable to ROS attack compromising its functionality, mirrored in terms of fertility outcome and making the study of the origin of sperm ROS, as well as the alterations they cause very important. In the present work, we used UVB irradiation, an easy experimental approach known as a potent inducer of ROS formation, to better understand the origin of ROS damage without any confounding effects that usually exist in disease models in which ROS are reported to play a role. To address these issues we evaluated sperm mitochondrial ROS production using the Mitosox Red Probe, mitochondrial membrane potential using the JC-1 probe, lipid peroxidation through BODIPY probe and vitality using PI. We observed that UVB irradiation leads to an increase in sperm mitochondrial ROS production and lipid peroxidation that occur previously to an observable mitochondrial dysfunction. We concluded that sperm UVB irradiation appears to be a good and easily manipulated in vitro model system to study mitochondria-induced oxidative stress in spermatozoa and its consequences, which may be relevant in terms of dissecting the action pathways of many other pathologies, drugs and contaminants, including endocrine disruptors.
    Andrology 07/2013; DOI:10.1111/j.2047-2927.2013.00098.x · 3.37 Impact Factor


Available from