Volume 5, Issue 4

Cite this Article

How to cite

Blagosklonny MV, . Big mice die young but large animals live longer. . 5:227-233. https://doi.org/10.18632/aging.100551

Copy or Download citation:

Select the format you require from the list below

• Plain text
• EndNote
• Reference Manager
• ProCite
• BibteX

Provider: TY - JOUR AU - Blagosklonny, Mikhail V. TI - Big mice die young but large animals live longer JO - JA - VL - 5 IS - 4 PB - SN - UR - https://doi.org/10.18632/aging.100551 DO - 10.18632/aging.100551 SP - 227 EP - 233 PY - ER -

Provider: TY - JOUR AU - Blagosklonny, Mikhail V. TI - Big mice die young but large animals live longer JO - JA - VL - 5 IS - 4 PB - SN - UR - https://doi.org/10.18632/aging.100551 DO - 10.18632/aging.100551 SP - 227 EP - 233 PY - AB - It has been known for millennia that large animals live longer, inspiring numerous theories of aging. For example, elephants and humans live longer than mice, which in turn live longer than worms and flies. The correlation is not perfect, with many explainable exceptions, but it is still obvious. In contrast, within each species (e.g., mice and some other mammals) small body size is associated with longevity and slow aging. The concept that aging (and age-related diseases) is an aimless continuation of developmental growth, a hyperfunction driven by the same nutrient-sensing and growth-promoting pathways such as MTOR, may explain this longstanding paradox. ER -

Click to copy this citation from the text box above or download the citation:

• Citation
• Citation & Abstract

Cite this Article

How to cite

Richard VR, Leonov A, Beach A, Burstein MT, Koupaki O, Gomez-Perez A, Levy S, Pluska L, Mattie S, Rafeh R, Iouk T, Sheibani S, Greenwood M, et al, . Macromitophagy is a longevity assurance process that in chronologically aging yeast limited in calorie supply sustains functional mitochondria and maintains cellular lipid homeostasis. . 5:234-269. https://doi.org/10.18632/aging.100547

Copy or Download citation:

Select the format you require from the list below

• Plain text
• EndNote
• Reference Manager
• ProCite
• BibteX

Provider: TY - JOUR AU - Richard, Vincent R. AU - Leonov, Anna AU - Beach, Adam AU - Burstein, Michelle T. AU - Koupaki, Olivia AU - Gomez-Perez, Alejandra AU - Levy, Sean AU - Pluska, Lukas AU - Mattie, Sevan AU - Rafeh, Rami AU - Iouk, Tatiana AU - Sheibani, Sara AU - Greenwood, Michael AU - Vali, Hojatollah AU - Titorenko, Vladimir I. TI - Macromitophagy is a longevity assurance process that in chronologically aging yeast limited in calorie supply sustains functional mitochondria and maintains cellular lipid homeostasis JO - JA - VL - 5 IS - 4 PB - SN - UR - https://doi.org/10.18632/aging.100547 DO - 10.18632/aging.100547 SP - 234 EP - 269 PY - ER -

Provider: TY - JOUR AU - Richard, Vincent R. AU - Leonov, Anna AU - Beach, Adam AU - Burstein, Michelle T. AU - Koupaki, Olivia AU - Gomez-Perez, Alejandra AU - Levy, Sean AU - Pluska, Lukas AU - Mattie, Sevan AU - Rafeh, Rami AU - Iouk, Tatiana AU - Sheibani, Sara AU - Greenwood, Michael AU - Vali, Hojatollah AU - Titorenko, Vladimir I. TI - Macromitophagy is a longevity assurance process that in chronologically aging yeast limited in calorie supply sustains functional mitochondria and maintains cellular lipid homeostasis JO - JA - VL - 5 IS - 4 PB - SN - UR - https://doi.org/10.18632/aging.100547 DO - 10.18632/aging.100547 SP - 234 EP - 269 PY - AB - Macromitophagy controls mitochondrial quality and quantity. It involves the sequestration of dysfunctional or excessive mitochondria within double-membrane autophagosomes, which then fuse with the vacuole/lysosome to deliver these mitochondria for degradation. To investigate a physiological role of macromitophagy in yeast, we examined how the atg32Δ-dependent mutational block of this process influences the chronological lifespan of cells grown in a nutrient-rich medium containing low (0.2%) concentration of glucose. Under these longevity-extending conditions of caloric restriction (CR) yeast cells are not starving. We also assessed a role of macromitophagy in lifespan extension by lithocholic acid (LCA), a bile acid that prolongs yeast longevity under CR conditions. Our findings imply that macromitophagy is a longevity assurance process underlying the synergistic beneficial effects of CR and LCA on yeast lifespan. Our analysis of how the atg32Δ mutation influences mitochondrial morphology, composition and function revealed that macromitophagy is required to maintain a network of healthy mitochondria. Our comparative analysis of the membrane lipidomes of organelles purified from wild-type and atg32Δ cells revealed that macromitophagy is required for maintaining cellular lipid homeostasis. We concluded that macromitophagy defines yeast longevity by modulating vital cellular processes inside and outside of mitochondria. ER -

Click to copy this citation from the text box above or download the citation:

• Citation
• Citation & Abstract

Cite this Article

How to cite

Brandstädt S, Schmeisser K, Zarse K, Ristow M, . Lipid-lowering fibrates extend C. elegans lifespan in a NHR-49/PPARalpha-dependent manner. . 5:270-275. https://doi.org/10.18632/aging.100548

Copy or Download citation:

Select the format you require from the list below

• Plain text
• EndNote
• Reference Manager
• ProCite
• BibteX

Provider: TY - JOUR AU - Brandstädt, Sven AU - Schmeisser, Kathrin AU - Zarse, Kim AU - Ristow, Michael TI - Lipid-lowering fibrates extend <i>C. elegans</i> lifespan in a NHR-49/PPARalpha-dependent manner JO - JA - VL - 5 IS - 4 PB - SN - UR - https://doi.org/10.18632/aging.100548 DO - 10.18632/aging.100548 SP - 270 EP - 275 PY - ER -

Provider: TY - JOUR AU - Brandstädt, Sven AU - Schmeisser, Kathrin AU - Zarse, Kim AU - Ristow, Michael TI - Lipid-lowering fibrates extend <i>C. elegans</i> lifespan in a NHR-49/PPARalpha-dependent manner JO - JA - VL - 5 IS - 4 PB - SN - UR - https://doi.org/10.18632/aging.100548 DO - 10.18632/aging.100548 SP - 270 EP - 275 PY - AB - Compounds that delay aging in model organisms may be of significant interest to anti-aging medicine, since these substances potentially provide pharmaceutical approaches to promote healthy lifespan in humans. We here aimed to test whether pharmaceutical concentrations of three fibrates, pharmacologically established serum lipid-lowering drugs and ligands of the nuclear receptor PPARalpha in mammals, are capable of extending lifespan in a nematodal model organism for aging processes, the roundworm Caenorhabditis elegans. Adult C. elegans (wild-type N2 as well as two nhr-49-deficient strains, RB1716 and VC870) were maintained on agar plates and were fed E. coli strain OP50 bacteria. Bezafibrate, clofibrate, and fenofibrate were applied to the agar, respectively, to test whether they may promote longevity by quantifying survival in the presence and absence of the respective compounds. All three fibrates extended C. elegans N2 lifespan when applied at a concentration of 10 micromolar. Bezafibrate additionally extended C. elegans N2 lifespan at concentrations of 1 micromolar and 0.1 micromolar. In strains deficient for nhr-49, a functional orthologue of the mammalian peroxisome proliferator-activated receptor alpha (PPARalpha), all three compounds were incapable of extending lifespan. Taken together, fibrates promote C. elegans longevity in an NHR-49-dependent manner possibly by promoting mitohormesis and suggesting that these compounds may promote lifespan also in mammals. ER -

Click to copy this citation from the text box above or download the citation:

• Citation
• Citation & Abstract

Cite this Article

How to cite

Scherfer C, Han VC, Wang Y, Anderson AE, Galko MJ, . Autophagy drives epidermal deterioration in a Drosophila model of tissue aging. . 5:276-287. https://doi.org/10.18632/aging.100549

Copy or Download citation:

Select the format you require from the list below

• Plain text
• EndNote
• Reference Manager
• ProCite
• BibteX

Provider: TY - JOUR AU - Scherfer, Christoph AU - Han, Violet C. AU - Wang, Yan AU - Anderson, Aimee E. AU - Galko, Michael J. TI - Autophagy drives epidermal deterioration in a Drosophila model of tissue aging JO - JA - VL - 5 IS - 4 PB - SN - UR - https://doi.org/10.18632/aging.100549 DO - 10.18632/aging.100549 SP - 276 EP - 287 PY - ER -

Provider: TY - JOUR AU - Scherfer, Christoph AU - Han, Violet C. AU - Wang, Yan AU - Anderson, Aimee E. AU - Galko, Michael J. TI - Autophagy drives epidermal deterioration in a Drosophila model of tissue aging JO - JA - VL - 5 IS - 4 PB - SN - UR - https://doi.org/10.18632/aging.100549 DO - 10.18632/aging.100549 SP - 276 EP - 287 PY - AB - Organismal lifespan has been the primary readout in aging research. However, how longevity genes control tissue-specific aging remains an open question. To examine the crosstalk between longevity programs and specific tissues during aging, biomarkers of organ-specific aging are urgently needed. Since the earliest signs of aging occur in the skin, we sought to examine skin aging in a genetically tractable model. Here we introduce a Drosophila model of skin aging. The epidermis undergoes a dramatic morphological deterioration with age that includes membrane and nuclear loss. These changes were decelerated in a long-lived mutant and accelerated in a short-lived mutant. An increase in autophagy markers correlated with epidermal aging. Finally, the epidermis of Atg7 mutants retained younger characteristics, suggesting that autophagy is a critical driver of epidermal aging. This is surprising given that autophagy is generally viewed as protective during aging. Since Atg7 mutants are short-lived, the deceleration of epidermal aging in this mutant suggests that in the epidermis healthspan can be uncoupled from longevity. Because the aging readout we introduce here has an early onset and is easily visualized, genetic dissection using our model should identify other novel mechanisms by which lifespan genes feed into tissue-specific aging. ER -

Click to copy this citation from the text box above or download the citation:

• Citation
• Citation & Abstract

Cite this Article

How to cite

Xiong Z, LaDana C, Wu D, Cao K, . An inhibitory role of progerin in the gene induction network of adipocyte differentiation from iPS cells. . 5:288-303. https://doi.org/10.18632/aging.100550

Copy or Download citation:

Select the format you require from the list below

• Plain text
• EndNote
• Reference Manager
• ProCite
• BibteX

Provider: TY - JOUR AU - Xiong, Zheng-Mei AU - LaDana, Christina AU - Wu, Di AU - Cao, Kan TI - An inhibitory role of progerin in the gene induction network of adipocyte differentiation from iPS cells JO - JA - VL - 5 IS - 4 PB - SN - UR - https://doi.org/10.18632/aging.100550 DO - 10.18632/aging.100550 SP - 288 EP - 303 PY - ER -

Provider: TY - JOUR AU - Xiong, Zheng-Mei AU - LaDana, Christina AU - Wu, Di AU - Cao, Kan TI - An inhibitory role of progerin in the gene induction network of adipocyte differentiation from iPS cells JO - JA - VL - 5 IS - 4 PB - SN - UR - https://doi.org/10.18632/aging.100550 DO - 10.18632/aging.100550 SP - 288 EP - 303 PY - AB - Lipodystrophies, characterized by partial or complete loss of adipose tissue, have been associated with mutations in the lamin A gene. It remains unclear how lamin A mutants interfere with adipose tissue formation. Hutchinson–Gilford progeria syndrome (HGPS) presents the most severe form of lamin A-associated diseases, whose patients show a complete loss of subcutaneous fat. Using iPSCs reprogrammed from HGPS fibroblasts, we induced adipocyte formation from iPSC derived embryoid bodies or from iPSC derived mesenchymal stem cells. Both approaches revealed a severe lipid storage defect in HGPS cells at late differentiation stage, faithfully recapitulating HGPS patient phenotype. Expression analysis further indicated that progerin inhibited the transcription activation of PPARγ2 and C/EBPα, but had little effects on the early adipogenic regulators. Our experiments demonstrate two comparable approaches of in vitro modeling lipodystrophies with patient-specific iPSCs, and support a regulatory role of lamin A in the terminal differentiation stage of adipogenesis. ER -

Click to copy this citation from the text box above or download the citation:

• Citation
• Citation & Abstract

Cite this Article

How to cite

Azpurua J, Yang J, Van Meter M, Liu Z, Kim J, Lobo Ladd AA, Coppi AA, Gorbunova V, Seluanov A, . IGF1R levels in the brain negatively correlate with longevity in 16 rodent species. . 5:304-314. https://doi.org/10.18632/aging.100552

Copy or Download citation:

Select the format you require from the list below

• Plain text
• EndNote
• Reference Manager
• ProCite
• BibteX

Provider: TY - JOUR AU - Azpurua, Jorge AU - Yang, Jiang-Nan AU - Van Meter, Michael AU - Liu, Zhengshan AU - Kim, Julie AU - Lobo Ladd, Aliny AB AU - Coppi, Antonio Augusto AU - Gorbunova, Vera AU - Seluanov, Andrei TI - IGF1R levels in the brain negatively correlate with longevity in 16 rodent species JO - JA - VL - 5 IS - 4 PB - SN - UR - https://doi.org/10.18632/aging.100552 DO - 10.18632/aging.100552 SP - 304 EP - 314 PY - ER -

Provider: TY - JOUR AU - Azpurua, Jorge AU - Yang, Jiang-Nan AU - Van Meter, Michael AU - Liu, Zhengshan AU - Kim, Julie AU - Lobo Ladd, Aliny AB AU - Coppi, Antonio Augusto AU - Gorbunova, Vera AU - Seluanov, Andrei TI - IGF1R levels in the brain negatively correlate with longevity in 16 rodent species JO - JA - VL - 5 IS - 4 PB - SN - UR - https://doi.org/10.18632/aging.100552 DO - 10.18632/aging.100552 SP - 304 EP - 314 PY - AB - The insulin/insulin-like growth factor signaling (IIS) pathway is a major conserved regulator of aging. Nematode, fruit fly and mouse mutants with reduced IIS signaling exhibit extended lifespan. These mutants are often dwarfs leading to the idea that small body mass correlates with longevity within species. However, when different species are compared, larger animals are typically longer-lived. Hence, the role of IIS in the evolution of life history traits remains unresolved. Here we used comparative approach to test whether IGF1R signaling changes in response to selection on lifespan or body mass and whether specific tissues are involved. The IGF1R levels in the heart, lungs, kidneys, and brains of sixteen rodent species with highly diverse lifespans and body masses were measured via immunoblot after epitope conservation analysis. We report that IGF1R levels display strong negative correlation with maximum lifespan only in brain tissue and no significant correlations with body mass for any organ. The brain-IGF1R and lifespan correlation holds when phylogenetic non-independence of data-points is taken into account. These results suggest that modulation of IGF1R signaling in nervous tissue, but not in the peripheral tissues, is an important factor in the evolution of longevity in mammals. ER -

Click to copy this citation from the text box above or download the citation:

• Citation
• Citation & Abstract

Cite this Article

How to cite

Hoffmann J, Romey R, Fink C, Yong L, Roeder T, . Overexpression of Sir2 in the adult fat body is sufficient to extend lifespan of male and female Drosophila. . 5:315-327. https://doi.org/10.18632/aging.100553

Copy or Download citation:

Select the format you require from the list below

• Plain text
• EndNote
• Reference Manager
• ProCite
• BibteX

Provider: TY - JOUR AU - Hoffmann, Julia AU - Romey, Renja AU - Fink, Christine AU - Yong, Li AU - Roeder, Thomas TI - Overexpression of <i>Sir2</i> in the adult fat body is sufficient to extend lifespan of male and female <i>Drosophila</i> JO - JA - VL - 5 IS - 4 PB - SN - UR - https://doi.org/10.18632/aging.100553 DO - 10.18632/aging.100553 SP - 315 EP - 327 PY - ER -

Provider: TY - JOUR AU - Hoffmann, Julia AU - Romey, Renja AU - Fink, Christine AU - Yong, Li AU - Roeder, Thomas TI - Overexpression of <i>Sir2</i> in the adult fat body is sufficient to extend lifespan of male and female <i>Drosophila</i> JO - JA - VL - 5 IS - 4 PB - SN - UR - https://doi.org/10.18632/aging.100553 DO - 10.18632/aging.100553 SP - 315 EP - 327 PY - AB - Sir2 is the most intensively discussed longevity gene in current aging research. Although, the gene encoding for a NAD+-dependent histone deacetylase initially was found to extend lifespan of various organisms ranging from yeast to mammals, serious doubts regarding its role in longevity have been expressed recently. In this study, we tested whether tissue-specific overexpression of Sir2 in the adult fat body can extend lifespan when compared to genetically identical controls. We also wanted to elucidate the mechanisms by which fat body Sir2 promotes longevity by studying the phenotypic and transcriptional changes in the fat body. We found that moderate (3-fold) Sir2 overexpression in the fat body during adulthood only can promote longevity in both sexes by roughly 13 %. In addition, we obtained transcriptional profiles elicited by this overexpression and propose a role for Sir2 in lipid droplet biology especially under conditions of starvation. Furthermore, our data do not support the idea of Sir2 mediating the response to dietary restriction (DR) because transcriptional profiles of fat bodies after DR or Sir2 overexpression do not match. This study provides additional independent evidence for the concept of Sir2 as a longevity gene and as a promising pharmacological target to cure age-related diseases. ER -

Click to copy this citation from the text box above or download the citation:

• Citation
• Citation & Abstract