Longevity network: Construction and implications

Budovsky, Arie; Abramovich, Amir; Cohen, Raphael; Chalifa‐Caspi, Vered; Fraifeld, Vadim E.

doi:10.1016/j.mad.2006.11.018

Cited by 87 publications

(90 citation statements)

References 55 publications

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“…These results might reflect, in human-chimpanzee gene pairs, a higher degree of conservation throughout evolution of genes whose homologs are involved in aging in non-mammalian model organisms. In fact, the proportion of human homologs of agingrelated genes in model organisms has been reported to be higher than expected by chance (Budovsky et al, 2007). This high conservation of aging-related genes might be related to their reported higher-than-average interactions (Promislow, 2004;Budovsky et al, 2007).…”

Section: Discussionmentioning

confidence: 93%

“…In fact, the proportion of human homologs of agingrelated genes in model organisms has been reported to be higher than expected by chance (Budovsky et al, 2007). This high conservation of aging-related genes might be related to their reported higher-than-average interactions (Promislow, 2004;Budovsky et al, 2007). Our results, albeit only explorative, do not appear to support the hypothesis that most genes and mechanisms that have been the focus of research in model organisms are likely to regulate species differences in aging, at least in primates.…”

Section: Discussionmentioning

confidence: 95%

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Analyses of human–chimpanzee orthologous gene pairs to explore evolutionary hypotheses of aging

Magalhães

Church

2007

Mechanisms of Ageing and Development

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Compared to chimpanzees (Pan troglodytes), the onset of aging appears to be delayed in the human species. Herein, we studied human-chimpanzee orthologous gene pairs to investigate the selective forces acting on genes associated with aging in different model systems, which allowed us to explore evolutionary hypotheses of aging. Our results show that aging-associated genes tend to be under purifying selection and stronger-than-average functional constraints. We found little evidence of accelerated evolution in aging-associated genes in the hominid or human lineages, and pathways previously related to aging were largely conserved between humans and chimpanzees. In particular, genes associated with aging in non-mammalian model organisms and cellular systems appear to be under stronger functional constraints than those associated with aging in mammals. One gene that might have undergone rapid evolution in hominids is the Werner syndrome gene. Overall, our findings offer novel insights regarding the evolutionary forces acting on genes associated with aging in model systems. We propose that genes associated with aging in model organisms may be part of conserved pathways related to pleiotropic effects on aging that might not regulate species differences in aging.

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Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 95%

Analyses of human–chimpanzee orthologous gene pairs to explore evolutionary hypotheses of aging

Magalhães

Church

2007

Mechanisms of Ageing and Development

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“…In some instances, single gene mutants have been observed to increase maximum life span by as much as 40% (3). Other studies have focused on identifying genes that are associated with longevity in humans-that is, genes observed to have a higher allele frequency in centenarians (4)(5)(6).…”

mentioning

confidence: 99%

“…Other studies have focused on identifying genes that are associated with longevity in humans-that is, genes observed to have a higher allele frequency in centenarians (4)(5)(6). However, such human longevity-associated genes (LAGs) seem to be very rare, and although a few have been confirmed in independent studies (2,3), their existence remains controversial. More recently, epigenetic changes associated with human longevity have also been documented (7).…”

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confidence: 99%

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Distinctive topology of age-associated epigenetic drift in the human interactome

West

Widschwendter

Teschendorff

2013

Proc. Natl. Acad. Sci. U.S.A.

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Recently, it has been demonstrated that DNA methylation, a covalent modification of DNA that can regulate gene expression, is modified as a function of age. However, the biological and clinical significance of this age-associated epigenetic drift is unclear. To shed light on the potential biological significance, we here adopt a systems approach and study the genes undergoing age-associated changes in DNA methylation in the context of a protein interaction network, focusing on their topological properties. In contrast to what has been observed for other age-related gene classes, including longevity-and disease-associated genes, as well as genes undergoing age-associated changes in gene expression, we here demonstrate that age-associated epigenetic drift occurs preferentially in genes that occupy peripheral network positions of exceptionally low connectivity. In addition, we show that these genes synergize topologically with disease and longevity genes, forming unexpectedly large network communities. Thus, these results point toward a potentially distinct mechanistic and biological role of DNA methylation in dictating the complex aging and disease phenotypes.biological networks | epigenomics | aging | network topology

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Molecular Biomarkers of Aging

2021

Encyclopedia of Gerontology and Population Aging

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Longevity network: Construction and implications

Cited by 87 publications

References 55 publications

Analyses of human–chimpanzee orthologous gene pairs to explore evolutionary hypotheses of aging

Analyses of human–chimpanzee orthologous gene pairs to explore evolutionary hypotheses of aging

Distinctive topology of age-associated epigenetic drift in the human interactome

Molecular Biomarkers of Aging

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