Longevity

Publication Title: 
Tijdschrift Voor Gerontologie En Geriatrie

The desire for the extension of life is not one out of many desire in life, but a form of the fundamental desire for life itself. This so called 'categorical desire' is a necessary condition for the many desires in life. The question why we desire for life (and for its extension), is the question for the meaning of life. The searching for a 'natural lifespan' is meaningless when it wants to find in nature a given norm for the duration of life. It can only have meaning when it tries to formulate the conditions for the experience of life as successful and meaningful.

Author(s): 
van Tongeren, P.
Publication Title: 
Nature Genetics

Reactive oxygen (RO) has been identified as an important effector in ageing and lifespan determination. The specific cell types, however, in which oxidative damage acts to limit lifespan of the whole organism have not been explicitly identified. The association between mutations in the gene encoding the oxygen radical metabolizing enzyme CuZn superoxide dismutase (SOD1) and loss of motorneurons in the brain and spinal cord that occurs in the life-shortening paralytic disease, Familial Amyotrophic Lateral Sclerosis (FALS; ref.

Author(s): 
Parkes, T. L.
Elia, A. J.
Dickinson, D.
Hilliker, A. J.
Phillips, J. P.
Boulianne, G. L.
Publication Title: 
Mechanisms of Ageing and Development

Accessible and readily utilized software, tables and approximation formulae have been developed to estimate power and sample size for studies of time to event (survival times) when the survival times are assumed to be exponential. These methods can markedly misestimate power when the distribution is Weibull and not exponential. The Weibull distribution with increasing hazard is common in aging research, especially when the whole life span of the subjects is of interest.

Author(s): 
Heo, M.
Faith, M. S.
Allison, D. B.
Publication Title: 
Free Radical Biology & Medicine

Mutations in human CuZn superoxide dismutase (SOD) have been associated with familial amyotrophic lateral sclerosis (FALS). Although leading to many experimental advances, this finding has not yet led to a clear understanding of the biochemical mechanism by which mutations in SOD promote the degeneration of motorneurons that causes this incurable paralytic disease.

Author(s): 
Elia, A. J.
Parkes, T. L.
Kirby, K.
St George-Hyslop, P.
Boulianne, G. L.
Phillips, J. P.
Hilliker, A. J.
Publication Title: 
The Journal of Nutrition, Health & Aging

Caloric restriction (CR), undernutrition without malnutrition, remains the only experimental paradigm that has been shown consistently to extend lifespan and slow aging in short-lived species. Decades of research, mostly in laboratory rodents, have shown that CR consistently extends lifespan, reduces or delays the onset of many age-related diseases and slows aging in many physiological systems. In recent years gerontologists interested in CR have focused on two unanswered questions. 1) What is the relevance of this nutritional paradigm to human aging?

Author(s): 
Lane, M. A.
Ingram, D. K.
Roth, G. S.
Publication Title: 
FEBS letters

Strains of Caenorhabditis elegans mutant for clk-1 exhibit a 20-40% increase in mean lifespan. clk-1 encodes a mitochondrial protein thought to be either an enzyme or regulatory molecule acting within the ubiquinone biosynthesis pathway. Here CLK-1 is shown to be related to the ubiquinol oxidase, alternative oxidase, and belong to the functionally diverse di-iron-carboxylate protein family which includes bacterioferritin and methane mono-oxygenase.

Author(s): 
Rea, S.
Publication Title: 
Ageing Research Reviews

Aging is a universal biological phenomenon in eukaryotes, but why and how we age still remain mysterious. It would be of great biological interest and practical importance if we could uncover the molecular mechanism of aging, and find a way to delay the aging process while maintaining physical and mental strengths of youth. Histone deacetylases (HDACs) such as SIR2 and RPD3 are known to be involved in the extension of lifespan in yeast and Caenorhabditis elegans.

Author(s): 
Chang, Karen T.
Min, Kyung-Tai
Publication Title: 
Nature

The nematode Caenorhabditis elegans is an important model for studying the genetics of ageing, with over 50 life-extension mutations known so far. However, little is known about the pathobiology of ageing in this species, limiting attempts to connect genotype with senescent phenotype. Using ultrastructural analysis and visualization of specific cell types with green fluorescent protein, we examined cell integrity in different tissues as the animal ages.

Author(s): 
Herndon, Laura A.
Schmeissner, Peter J.
Dudaronek, Justyna M.
Brown, Paula A.
Listner, Kristin M.
Sakano, Yuko
Paupard, Marie C.
Hall, David H.
Driscoll, Monica
Publication Title: 
Aging Cell

Molecular advances of the past decade have led to the discovery of a myriad of 'aging genes' (methuselah, Indy, InR, Chico, superoxide dismutase) that extend Drosophila lifespan by up to 85%. Despite this life extension, these mutants are no longer lived than at least some recently wild-caught strains. Typically, long-lived mutants are identified in relatively short-lived genetic backgrounds, and their effects are rarely tested in genetic backgrounds other than the one in which they were isolated or derived.

Author(s): 
Spencer, Christine C.
Howell, Christine E.
Wright, Amber R.
Promislow, Daniel E. L.
Publication Title: 
Nature

Calorie restriction extends lifespan in organisms ranging from yeast to mammals. In yeast, the SIR2 gene mediates the life-extending effects of calorie restriction. Here we show that the mammalian SIR2 orthologue, Sirt1 (sirtuin 1), activates a critical component of calorie restriction in mammals; that is, fat mobilization in white adipocytes. Upon food withdrawal Sirt1 protein binds to and represses genes controlled by the fat regulator PPAR-gamma (peroxisome proliferator-activated receptor-gamma), including genes mediating fat storage.

Author(s): 
Picard, FrÈdÈric
Kurtev, Martin
Chung, Namjin
Topark-Ngarm, Acharawan
Senawong, Thanaset
Machado De Oliveira, Rita
Leid, Mark
McBurney, Michael W.
Guarente, Leonard

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