Modulation of PPAR in Aging, Inflammation, and Calorie Restriction

Sung, Bokyung; Park, Seong Joon; Yu, Byung Pal; Chung, Hae Young

doi:10.1093/gerona/59.10.b997

Cited by 135 publications

(105 citation statements)

References 36 publications

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“…19 -21 Previous studies in the kidney showed that PPAR␥ activity was decreased in aging rats. 12 Our data showed that pioglitazone increased PPAR␥ expression and activity in the aging kidney, which paralleled decreased glomerulosclerosis and interstitial fibrosis. In addition, systemic oxidative stress and intima thickness in renal arteries were decreased in the treatment group (data not shown).…”

Section: Discussionsupporting

confidence: 51%

“…11 However, there is little information about PPAR modulation during aging. Because expression of PPAR␥ is reduced during aging and TZDs have many beneficial effects on aging-related molecules, 12 we hypothesized that pioglitazone could protect against aging-related renal injury. Our results indeed show that activation of PPAR␥ is protective against aging-related renal injury.…”

mentioning

confidence: 99%

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The PPARγ Agonist Pioglitazone Ameliorates Aging-Related Progressive Renal Injury

Yang

Deleuze²,

Zuo³

et al. 2009

Journal of the American Society of Nephrology

160

108

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Peroxisome proliferator-activated receptor-␥ (PPAR-␥) agonists not only improve metabolic abnormalities of diabetes and consequent diabetic nephropathy, but they also protect against nondiabetic chronic kidney disease in experimental models. Here, we found that the PPAR-␥ agonist pioglitazone protected against renal injury in aging; it reduced proteinuria, improved GFR, decreased sclerosis, and alleviated cell senescence. Increased local expression of PPAR-␥ paralleled these changes. Underlying mechanisms included increased expression of klotho, decreased systemic and renal oxidative stress, and decreased mitochondrial injury. Pioglitazone also regulated p66Shc phosphorylation, which integrates many signaling pathways that affect mitochondrial function and longevity, by reducing protein kinase C-␤. These results suggest that PPAR-␥ agonists may benefit aging-related renal injury by improving mitochondrial function.

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Section: Discussionsupporting

confidence: 51%

mentioning

confidence: 99%

The PPARγ Agonist Pioglitazone Ameliorates Aging-Related Progressive Renal Injury

Yang

Deleuze²,

Zuo³

et al. 2009

Journal of the American Society of Nephrology

160

108

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“…In rodents, PPARs seem to play an important role in the delay of aging caused by CR (86,312). In the rat, PPAR nuclear protein, mRNA level, and DNA-binding activity were shown to decrease with age, whereas CR blunted these reductions (391). Alternatively, using microarray technology, PPAR target genes were upregulated early and intensely in the livers of CR mice (22).…”

Section: Calorie Restriction and Agingmentioning

confidence: 99%

Angiotensin II blockade: how its molecular targets may signal to mitochondria and slow aging. Coincidences with calorie restriction and mTOR inhibition

Cavanagh

Inserra

Ferder

2015

American Journal of Physiology-Heart and Circulatory Physiology

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de Cavanagh EM, Inserra F, Ferder L. Angiotensin II blockade: how its molecular targets may signal to mitochondria and slow aging. Coincidences with calorie restriction and mTOR inhibition. Am J Physiol Heart Circ Physiol 309: H15-H44, 2015. First published May 1, 2015; doi:10.1152/ajpheart.00459.2014, renin angiotensin system blockade (RAS-bl), and rapamycin-mediated mechanistic target of rapamycin (mTOR) inhibition increase survival and retard aging across species. Previously, we have summarized CR and RAS-bl's converging effects, and the mitochondrial function changes associated with their physiological benefits. mTOR inhibition and enhanced sirtuin and KLOTHO signaling contribute to the benefits of CR in aging. mTORC1/mTORC2 complexes contribute to cell growth and metabolic regulation. Prolonged mTORC1 activation may lead to age-related disease progression; thus, rapamycin-mediated mTOR inhibition and CR may extend lifespan and retard aging through mTORC1 interference. Sirtuins by deacetylating histone and transcription-related proteins modulate signaling and survival pathways and mitochondrial functioning. CR regulates several mammalian sirtuins favoring their role in aging regulation. KLOTHO/fibroblast growth factor 23 (FGF23) contribute to control Ca 2ϩ , phosphate, and vitamin D metabolism, and their dysregulation may participate in age-related disease. Here we review how mTOR inhibition extends lifespan, how KLOTHO functions as an aging suppressor, how sirtuins mediate longevity, how vitamin D loss may contribute to age-related disease, and how they relate to mitochondrial function. Also, we discuss how RAS-bl downregulates mTOR and upregulates KLOTHO, sirtuin, and vitamin D receptor expression, suggesting that at least some of RAS-bl benefits in aging are mediated through the modulation of mTOR, KLOTHO, and sirtuin expression and vitamin D signaling, paralleling CR actions in age retardation. Concluding, the available evidence endorses the idea that RAS-bl is among the interventions that may turn out to provide relief to the spreading issue of age-associated chronic disease. mechanistic target of rapamycin; vitamin D; caloric restriction; renin-angiotensin system EFFORTS AIMED AT DECIPHERING the mechanisms that underlie the aging process have unveiled three interventions that can increase survival and retard age-related diseases from lower organisms to mammals, i.e., caloric restriction (CR) (84,85,140,160,334), mechanistic target of rapamycin (mTOR; originally mammalian TOR) inhibition by rapamycin (173,196,281), and renin-angiotensin system blockade (RAS-bl) (20, 21, 26,63,253,284,354), although the latter has been less studied. In light of these findings, some intriguing questions come to mind: Do these interventions attenuate aging by interfering with common mechanisms? Do the mechanisms that are interfered with by CR, rapamycin, and RAS-bl mutually affect each other? Are there any pathways involved exclusively with a certain intervention?Previously (101), we have discussed the converging effects d...

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“…In particular, the activity of genes involved in PPARγ-dependent adipogenesis is shown to decline with age for AL animals but not for CR animals (Mueller et al 2002). Linford et al (2007) also reported that PPARγ gene expression is reduced with age, but is preserved with CR in WAT, as was similarly found in other tissues (Sung et al 2004;Chung et al 2008). Furthermore, Wang et al (2008) recently demonstrated that decreased adipocyte storage capacity induces lipid accumulation in liver, heart, and skeletal muscle of the db/db-aP2-leptin receptor on an aP2 promoter (Lepr-b) transgenic mice and that ectopic lipid accumulation is related to metabolic syndrome, including T2D.…”

Section: Discussionmentioning

confidence: 71%

Changes in lipid distribution during aging and its modulation by calorie restriction

Kim

Choi

et al. 2009

AGE

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Adipogenesis and ectopic lipid accumulation during aging have a great impact on the aging process and the pathogenesis of chronic diseases with age. However, at present, information on the agerelated molecular changes in lipid redistribution patterns and their potential nutritional interventions is sparse. We investigated the mechanism underlying age-related lipid redistribution and its modulation using 5-, 17-, and 24-month-old male Fischer 344 rats fed ad libitum (AL) or a 3-week-long CR (40% less than AL) diet. Results revealed that the activities of adipogenic transcription factors were decreased in the white adipose tissue (WAT) of aged AL rats. In contrast, the skeletal muscle of aged AL rats showed increased fat accumulation through decreased carnitine palmitoyltransferase-1 activity, which was blunted by short-term CR. This study suggests an age-related shift in lipid distribution by reducing the adipogenesis of WAT while increasing intramyocellular lipid accumulation, and that CR can modulate age-related adipogenesis and ectopic lipid accumulation.

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Modulation of PPAR in Aging, Inflammation, and Calorie Restriction

Cited by 135 publications

References 36 publications

The PPARγ Agonist Pioglitazone Ameliorates Aging-Related Progressive Renal Injury

The PPARγ Agonist Pioglitazone Ameliorates Aging-Related Progressive Renal Injury

Angiotensin II blockade: how its molecular targets may signal to mitochondria and slow aging. Coincidences with calorie restriction and mTOR inhibition

Changes in lipid distribution during aging and its modulation by calorie restriction

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