Denigma

Datasets

Changes

Denigma cartographies changes from the molecular level to whole physiology which occur in defined contrasts such as aging and dietary as well as genetic lifespan-extending interventions:

  • aging (young vs. old)
  • dietary (DR vs. AL)
  • genetic (mutant vs. wild-type) o
ID name taxid reference pmid tissue comparision start stop gender description
115 Hsp26 induction 4932 Herbert et al. in press — — diet DR (0.5% glucose) AL (2% glucose) — High osmolarity upregulates Hsp26 levels [Herbert et al. in press].
116 Hsp31 induction 4932 Herbert et al. in press — — diet DR (0.5% glucose) AL (2% glucose) — High osmolarity upregulates Hsp31 levels [Herbert et al. in press].
117 Lys9 induction 4932 Herbert et al. in press — — diet DR (0.5% glucose) AL (2% glucose) — High osmolarity upregulates Lys9 levels [Herbert et al. in press].
118 Rtc3 induction 4932 Herbert et al. in press — — diet DR (0.5% glucose) AL (2% glucose) — High osmolarity upregulates Rtc3 levels [Herbert et al. in press].
119 Rgi1 induction 4932 Herbert et al. in press — — diet DR (0.5% glucose) AL (2% glucose) — High osmolarity upregulates Rgi1 levels [Herbert et al. in press].
120 Oye2 induction 4932 Herbert et al. in press — — diet DR (0.5% glucose) AL (2% glucose) — High osmolarity upregulates Oye2 levels [Herbert et al. in press].
121 Smaller body size 6239 — 22810224 — mutation eat-2 wild-type — eat-2 mutants are noticeable smaller than wild-type [22810224].
130 Melatonin decreases — — 18212404 — age old young — Melatonin level decrease with age [reviewed in 18212404].
131 Arterial walls stiffen with age — López-Andrés et al. 2012 23172930 — — — — — Age-associated changes in blood vessels include the increase in inflammatory response, cell loss, inability to repair DNA damage, oncogene activation and regulation of telomere-telomerase complex [9-11]. Several age-associated structural, functional, and molecular changes occur in the arterial system. Aging is accompanied with thickening and dilatation of large arteries, extracellular matrix accumulation, calcium deposits, increased vascular stiffness, and endothelial dysfunction [12,13]. These alterations may be attributable to age-related functional changes in vascular cells [12]. Age-related arterial inflammatory phenotype includes increased expression of monocyte chemoattractant protein 1, intercellular adhesion molecule 1, matrix metalloproteinase-2 activity, or transforming growth factor-β expression [14,15]. Age-associated changes in blood vessels include a decrease in compliance, and increase in arterial stiffness and arterial wall thickening as a result of increased vascular calcifications, increased collagen content and cross-linking, and decreased elastin content [16,18]. References =========== 9. Lakatta EG. Cardiovascular regulatory mechanisms in advanced age. Physiol Rev. 1993;73:413–467. 10. Serrano M, Blasco MA. Putting the stress on senescence. Curr Opin Cell Biol. 2001;13:748–753. 11. Wei JY. Age and the cardiovascular system. N Engl J Med. 1992;327:1735–1739. 12. Lakatta EG. Arterial and cardiac aging: major shareholders in cardiovascular disease enterprises: Part III: cellular and molecular clues to heart and arterial aging. Circulation. 2003;107:490–497. 13. Lakatta EG, Wang M, Najjar SS. Arterial aging and subclinical arterial disease are fundamentally intertwined at macroscopic and molecular levels. Med Clin North Am. 2009;93:583–604, Table of Contents. 14. Spinetti G, Wang M, Monticone R, Zhang J, Zhao D, Lakatta EG. Rat aortic MCP-1 and its receptor CCR2 increase with age and alter vascular smooth muscle cell function. Arterioscler Thromb Vasc Biol. 2004;24:1397–1402. 15. Wang M, Zhao D, Spinetti G, Zhang J, Jiang LQ, Pintus G, Monticone R, Lakatta EG. Matrix metalloproteinase 2 activation of transforming growth factor-beta1 (TGF-beta1) and TGF-beta1-type II receptor signaling within the aged arterial wall. Arterioscler Thromb Vasc Biol. 2006;26:1503–1509. 16. Lacolley P, Labat C, Pujol A, Delcayre C, Benetos A, Safar M. Increased carotid wall elastic modulus and fibronectin in aldosterone-salt-treated rats: effects of eplerenone. Circulation. 2002;106:2848–2853. 17. López-Andrés N, Martin-Fernandez B, Rossignol P, Zannad F, Lahera V, Fortuno MA, Cachofeiro V, Díez J. A role for cardiotrophin-1 in myocardial remodeling induced by aldosterone. Am J Physiol Heart Circ Physiol. 2011;301:H2372–H2382. 18. Zieman SJ, Melenovsky V, Kass DA. Mechanisms, pathophysiology, and therapy of arterial stiffness. Arterioscler Thromb Vasc Biol.2005;25:932–943.
64 Decrease in WNT gene expression 9606 RoSyBa 2011 — adipose-derived stem cells age 40 year 60 year females A dramtic decrease in WNT gene expression occurs in Adipose-dreived stem cells from females at the age of 40-60 years [RoSyBa 2011].
86 Clonal mosicaism frequency increases 9505 Hunter et al. 2012 — blood — 50 79 female/male Detectable clonal mosaicism frequency in peripheral blood is low (<0.5 %) from birth until 50 years of age, after which it rapidley rises to 2-3% in the elderly. The frequency of mosic abnormalities increases with age, from 0.23% under 50 years to 1.91% between 75 and 79 years [Hunter et al. 2012].
67 Bone loss 10090 — 13678781 bone age 42 week 104 week male In young mice the rapid growth is marked by substantial increase in bone size, mineral mass and mechanical properties. Maturation occurring between 12 and 42 weeks of age was characterized with the maintenance of bone mass and mechanical properties. From the peak levels, mice aged for 104 weeks exhibited decreased whole femur mass, percentage of mineralization diminished whole bone stiffness, energy to fracture and decreased cortical thickness. Periosteal perimeter and, consequently the cross-sectional moments of inertia continued to increase through 104 weeks, compensating for cortical thinning and increased brittleness due to decreased mineralization and stiffness. The shape of the mid-diaphysis became increasingly less elliptical in aged mice. After 52 weeks excessive endocortical resorption appeared, indicating a shift in normal mechanisms regulating bone shape and locating, suggestive of remodelling [13678781].
129 Accumulation of long-chain glycosphingolipids 10090 — 21687659 brain age 17 months 3 months — Measurement of sphingolipid profiles in young (3 months), middle aged (9 moths) and old (17 months) C57BL/6 mice in brain reveals a dramatic elevations in long-chain hexosylceramides (HexCer) and lactosylceramides, with C14- and C16-lactosylcermaides (LacCers) elevated as much as 8 and 12-fold, respectively. Similar changes occur in kidney and liver [21687659].
126 Elevated long-chain lactosylceramides 9606 — 21687659 fibroblasts age old young — Long-chain lactosylceramides (LacCers) are significantly elevated in human fibroblasts isolated from elderly individuals [21687659].
58 Hippocampal atrophy 9606 — — Hippocampus age 56 84 males/females Shrinkage of hippocampus occurs with age. Several genes and genomic loci are associated with this process, among them are genes implicated in cell death (HRK), embryonic development (WIF1), diabetes (DPP) and neuronal migration (ASTN2) [22504421;22504417].
40 Accumulation of lipofuscin-like fluorescent pigment 6239 Apfeld et al., 2004 15574588 intestine Age 1 day 7 day Hemaphrodite A lipofuscin-like fluorescent pigment accumulates in an age-dependent manner in the intestine (Garigan et al., 2002; Herndon et al., 2002). It accumulates at a faster rate in aak-2 mutant, which have a shortened lifespan [15574588].
127 Accumulation of long-chain glycosphingolipids 10090 — 21687659 kidney age 17 month 3 month — Measurement of sphingolipid profiles in young (3 months), middle aged (9 moths) and old (17 months) C57BL/6 mice in kidney reveals a dramatic elevations in long-chain hexosylceramides (HexCer) and lactosylceramides, with C14- and C16-lactosylcermaides (LacCers) elevated as much as 8 and 12-fold, respectively. Similar changes occur in liver and brain. DR prevents the decline in kidney function, inhibits the accumulation of long-chain HexCer/LacCers and and also prevents the age-associated elevation of enzymes involved in their synthesis [21687659].
122 Lysosomal cholesterol content decreases 10116 Fusheng Tang, personal communication — liver age young old — In rat liver cells, the content of cholesterol in the lysosomal membrane decreases with age in spite of the overall increase of total cellular sterols.
123 Cellular liver sterol content increases 10116 [Fusheng Tang, personal communication — liver age old young — Overall the total cellular sterol content in liver increases with age [Fusheng Tang, personal communication].
128 Accumulation of long-chain glycosphingolipids 10090 — 21687659 liver age 17 months 3 months — Measurement of sphingolipid profiles in young (3 months), middle aged (9 moths) and old (17 months) C57BL/6 mice in liver reveals a dramatic elevations in long-chain hexosylceramides (HexCer) and lactosylceramides, with C14- and C16-lactosylcermaides (LacCers) elevated as much as 8 and 12-fold, respectively. Similar changes occur in kidney and brain [21687659].
41 Mitochondrial dysfunction increases 9606 Petersen et al., 2003 12750520 muscle Age — — — Aging is accompanied by an increase in mitochondrial dysfunction in muscle of humans [12750520].
98 Shift in metabolism towards increasing fatty acid syntheses and breakdown 7227 Katewa et al. 2012 — muscle diet DR (0.5% yeast extract) AL (5% yeast extract) female/male Flies on DR shift their metabolism toward increasing fatty acid synthesis and breakdown, specifically in muscle tissues, which is required for varoius responses to DR [22768842].
124 Reduced expression of autophagy genes 7227 — 18059160 neural age old young — The expression of several autophagy genes is reduced in neural tissues as a normal part of aging [18059160].
125 Insoluble ubiquitinated proteins accumulate 7227 — 18059160 neuronal age old young — Insoluble ubiquitinated proteins, markers of neuronal aging and degeneration, accumulate with aging in concomitantly with the age-dependent suppression of autopagy [18059160].
3 HDL decreases 10090 Wijeyesekera et al., 2012 22225495 Plasma Diet 30% DR for 48h at 16 weeks — male —

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