Mitochondrial biogenesis and healthy aging

Abstract

Aging is associated with an overall loss of function at the level of the whole organism that has origins in cellular deterioration. Most cellular components, including mitochondria, require continuous recycling and regeneration throughout the lifespan. Mitochondria are particularly susceptive to damage over time as they are the major bioenergetic machinery and source of oxidative stress in cells. Effective control of mitochondrial biogenesis and turnover, therefore, becomes critical for the maintenance of energy production, the prevention of endogenous oxidative stress and the promotion of healthy aging. Multiple endogenous and exogenous factors regulate mitochondrial biogenesis through the peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α). Activators of PGC-1α include nitric oxide, CREB and AMPK. Calorie restriction (CR) and resveratrol, a proposed CR mimetic, also increase mitochondrial biogenesis through activation of PGC-1α. Moderate exercise also mimics CR by inducing mitochondrial biogenesis. Negative regulators of PGC-1α such as RIP140 and 160MBP suppress mitochondrial biogenesis. Another mechanism involved in mitochondrial maintenance is mitochondrial fission/fusion and this process also involves an increasing number of regulatory proteins. Dysfunction of either biogenesis or fission/fusion of mitochondria is associated with diseases of the neuromuscular system and aging, and a greater understanding of the regulation of these processes should help us to ultimately control the aging process.

Changes in mitochondrial energy utilization in young and old worker honeybees (Apis mellifera)

“…This result is in accord with previous studies showing that ΔΨm decreases with advancing age in the hepatocytes of rats and mice (Hagen et al 1997;Kokoszka et al 2001), in the lymphocytes of mice (Wikowski and Micklem 1985;Rottenberg and Wu 1997), and hearts of rats (Savitha and Panneerselvam 2006). This phenomenon is the result of mitochondrial dysfunction during the aging process (Ames et al 1995;Trifunovic and Larsson 2008;Artal-Sanz and Tavernarakis 2008;López-Lluch et al 2008;Chanséaume and Morio 2009). In addition, the extended life span that accompanies TR, noted above, is associated with high ΔΨm (Hsu and Chiu 2009).…”

“…This result is consistent with previous studies showing that senescent human diploid fibroblasts have a high mitochondrial density (Martinez et al 1991;Xu and Finkel 2002) and that mitochondrial density increased in the lungs and brains of old humans (Lee et al 1998;Barrientos et al 1997;Lee et al 2000); livers, hearts, and brains of old rats (Gadaleta et al 1992); and the livers of old mice, rats, guinea pigs, rabbits, sheep, cows, hamsters, and humans (Passos et al 2007). This phenomenon principally reflects the low turnover of mitochondria and the accumulation of modified lipids, proteins, and DNA during the aging process, which leads to mitochondrial dysfunction and a decline in mitochondrial efficacy (Papa 1996;Wei 1998;López-Lluch et al 2008;Navarro and Boveris 2007;Choksi et al 2007). This interpretation is supported by a recent study showing that lipid peroxidation and protein oxidation increase with advancing age in the trophocytes and fat cells of workers reared in a field hive (Hsieh and Hsu 2011a).…”

Effects of intrinsic aerobic capacity, aging and voluntary running on skeletal muscle sirtuins and heat shock proteins

“…These findings raise the possibility that the muscle acts as an aging-sensitive tissue and the earlier onset of age-related degeneration in muscle may affect aging at the whole-body level (Demontis et al 2013). Aging in general is associated with a reduction in mitochondrial function and capacity (Lopez-Lluch et al 2008;Anderson & Prolla 2009), which eventually can be seen as a loss of physical function at the whole-body level.…”

Dietary fat composition influences glomerular and proximal convoluted tubule cell structure and autophagic processes in kidneys from calorie-restricted mice

“…Although the mechanisms by which CR operates are not completely understood, it is often assumed that the anti‐aging action of CR is partially based on its ability to suppress oxidative stress and maintain the cellular redox status to provide optimal cell signaling processes and normal gene expression (Chung et al ., 2013). Also, CR has been proposed to induce biogenesis of efficient mitochondria (López‐Lluch et al ., 2008). …”