Energy Metabolism

Publication Title: 
Mechanisms of Ageing and Development

The quest to understand why we age has given rise to numerous lines of investigation that have gradually converged to include metabolic control by mitochondrial activity as a major player. That is, the ideal balance between nutrient uptake, its transduction into usable energy, and the mitigation of damaging byproducts can be regulated by mitochondrial respiration and output (ATP, reactive oxygen species (ROS), and heat). Mitochondrial inefficiency through proton leak, which uncouples substrate oxidation from ADP phosphorylation, can comprise as much as 30% of the basal metabolic rate.

Mookerjee, Shona A.
Divakaruni, Ajit S.
Jastroch, Martin
Brand, Martin D.
Publication Title: 
Mechanisms of Ageing and Development

Despite the fact that ageing necessarily displays unique aspects in a single-cell organism, yeast, in particular Saccharomyces cerevisiae, are useful as model organisms to study ageing. Here we review mitochondrial characteristics involved in yeast longevity, including biogenesis, autophagy, respiration and oxidative phosphorylation, nutrient sensing, mitochondria-nuclear signaling, redox state and mitochondrial DNA integrity.

Barros, Mario H.
da Cunha, Fernanda M.
Oliveira, Graciele A.
Tahara, Erich B.
Kowaltowski, Alicia J.
Publication Title: 
Rejuvenation Research

According to the Homeric Hymn to Aphrodite, when Eos asked Zeus for Tithonus to be granted immortality, she forgot to ask for eternal youth. Applied Healthspan Engineering (AHE) seeks to address this problem. All organisms have a minimal level of functional reserve required to sustain life that eventually declines to a point incompatible with survival at death. AHE seeks to maintain or restore optimal functional reserve of critical tissues and organs. Tissue reserve correlates with well being.

Larrick, James W.
Mendelsohn, Andrew
Publication Title: 
Biochimica Et Biophysica Acta

Cellular processes such as proliferation, differentiation and death are intrinsically dependent upon the redox status of a cell. Among other indicators of redox flux, cellular NAD(H) levels play a predominant role in transcriptional reprogramming. In addition to this, normal physiological functions of a cell are regulated in response to perturbations in NAD(H) levels (for example, due to alterations in diet/metabolism) to maintain homeostatic conditions.

Ghosh, Sanchari
George, Suji
Roy, Upasana
Ramachandran, Deepti
Kolthur-Seetharam, Ullas
Publication Title: 
Research in Sports Medicine (Print)

The sirtuin family of proteins consists of seven members in mammals (SirT1-T7). Sirtuins share NAD dependency for their enzymatic activity, but some show NAD-dependent deacetylase activity, others exhibit ADP ribosyltransferase activity or both. Sirtuins have gained considerable attention due to their impact as physiological targets for treating diseases associated with aging. Sirtuins interact with metabolic pathways and may serve as entry points for drugs. This review discusses the biology of sirtuins and their potential as mediators of caloric restriction and pharmacological targets.

Lappalainen, Zekine
Publication Title: 
Experimental Gerontology

Apolipoprotein D (ApoD), a member of the Lipocalin family, is the gene most up-regulated with age in the mammalian brain. Its expression strongly correlates with aging-associated neurodegenerative and metabolic diseases. Two homologues of ApoD expressed in the Drosophila brain, Glial Lazarillo (GLaz) and Neural Lazarillo (NLaz), are known to alter longevity in male flies. However, sex differences in the aging process have not been explored so far for these genes.

Ruiz, Mario
Sanchez, Diego
Canal, Inmaculada
Acebes, Angel
Ganfornina, Maria D.
Publication Title: 
Integrative and Comparative Biology

More than 100 years ago, Max Rubner combined the fact that both metabolic rate and longevity of mammals varies with body size to calculate that "life energy potential" (lifetime energy turnover per kilogram) was relatively constant. This calculation linked longevity to aerobic metabolism which in turn led to the "rate-of-living" and ultimately the "oxidative stress" theories of aging. However, the link between metabolic rate and longevity is imperfect.

Hulbert, A. J.
Publication Title: 

Malnutrition is common among older persons, with important consequences increasing frailty and morbidity and reducing health expectancy. On the contrary, calorie restriction (CR, a low-calorie dietary regimen with adequate nutrition) slows the progression of age-related diseases and extends the lifespan of many species. Identification of strategies mimicking key CR mechanisms - increased mitochondrial respiration and reduced production of oxygen radicals - is a hot topic in gerontology.

Valerio, Alessandra
D'Antona, Giuseppe
Nisoli, Enzo
Publication Title: 

Calorie restriction results in leanness, which is linked to metabolic conditions that favor longevity. We show here that deficiency of the triglyceride synthesis enzyme acyl CoA:diacylglycerol acyltransferase 1 (DGAT1), which promotes leanness, also extends longevity without limiting food intake. Female DGAT1-deficient mice were protected from age-related increases in body fat, tissue triglycerides, and inflammation in white adipose tissue. This protection was accompanied by increased mean and maximal life spans of ~25% and ~10%, respectively.

Streeper, Ryan S.
Grueter, Carrie A.
Salomonis, Nathan
Cases, Sylvaine
Levin, Malin C.
Koliwad, Suneil K.
Zhou, Ping
Hirschey, Mattew D.
Verdin, Eric
Farese, Robert V.
Publication Title: 
Mechanisms of Ageing and Development

Caloric restriction (CR) slows the aging process and extends longevity, but the exact underlying mechanisms remain debatable. It has recently been suggested that the beneficial action of CR may be mediated in part by adipose tissue remodeling. Mammals have two types of adipose tissue: white adipose tissue (WAT) and brown adipose tissue (BAT). In this study, proteome analysis using two-dimensional gel electrophoresis combined with MALDI-TOF MS, and subsequent analyses were performed on both WAT and BAT from 9-month-old male rats fed ad libitum or subjected to CR for 6 months.

Okita, Naoyuki
Hayashida, Yusuke
Kojima, Yumiko
Fukushima, Mayumi
Yuguchi, Keiko
Mikami, Kentaro
Yamauchi, Akiko
Watanabe, Kyoko
Noguchi, Mituru
Nakamura, Megumi
Toda, Toshifusa
Higami, Yoshikazu


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