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
14 2-hydroxyisobutyrate increases 10090 Wijeyesekera et al., 2012 22225495 Plasma Mutant Irs1df/df at 16 weeks — male —
94 7alpha-dihydroxy-4-cholesten-4-one decrease 10090 — 22661299 serum age 3 months 22 months female Serum levels of 7alpha-dihydroxy-4-cholesten-4-one decreases from 3 to 33 months [22661299].
56 Ability to make decisions in novel sitations decreases 9606 Samanez-Larkin et al., 2012 22496578 — age 21 year 85 year males/females The ability to make decisions in novel sitations decreases with age from 21 to 85 years [22496578].
90 Accumulation of DNA damage 10090 — — — age — — — DNA damage accumulates with age in mouse hematopoietic stem cells [32 in Lauri et al. 2012].
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].
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].
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].
15 Acetate decreases 10090 Wijeyesekera et al., 2012 22225495 Plasma Mutant Irs1df/df at 16 weeks — male —
21 Acetoacetate increases 10090 Wijeyesekera et al., 2012 22225495 Plasma Diet 30% DR for 48h at 16 weeks — male —
36 alpha- and beta-glucose decreases 10090 Wijeyesekera et al., 2012 22225495 Plasma Diet 30% DR for 48h at 16 weeks — male —
39 AMP/ATP increases 6239 Apfeld et al., 2004 15574588 whole body Age 4 day 18 day Hemaphrodite AMP/ATP ratio in living animals increases from <0.1 at day 4 of adulthood to 0.8 at day 18 (an age near the maximum lifespan of the population). Linear regression indicates a strong correlation between AMP/ATP ratio and life expectancy.
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.
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].
85 Cell proliferation decreases 10116 — 11744049 — Diet — — — 24 month DR in rats inhibits cell proliferation in glandular stomach and liver tissue [11744049].
84 Cell proliferation increases 1016 11744049 — — Diet — — — 24 month DR in rats enhances cell proliferation in duodenum and forestomach mucosal tissue [11744049].
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].
95 Ceramides increase — — — — age — — — Sphingosine-linked fatty acids like ceramides serve as "damage-associated molecular patterns" (DAMPs) are increased in aged tissue and cause inflammatory damage via activation of Nlrp3 inflammasome [Vandanmagsar et al. 2011; Youm et al. 2012].
29 Choline decreases 10090 Wijeyesekera et al., 2012 22225495 Plasma Diet 30% DR for 48h at 16 weeks — male —
89 Chromosomal anomalies 969 — — — age — — — Chromosomal anomalies (rearrangements and aneuploidies) during cell division increases with age in cultured lymphocytes and fibroblasts [30,31 in Lauri et al. 2012].
80 Cisd2 expression declines — — 22661501 — age — — — Cisd2 expression decreases with age [22661501].
24 Citrate decreases 10090 Wijeyesekera et al., 2012 22225495 Plasma Diet 30% DR for 48h at 16 weeks — male —
25 Citrate increases 10099 Wijeyesekera et al., 2012 22225495 Plasma Mutant Irs1-/- at 16 weeks — male —
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].
111 Ctt1 induction 4932 Herbert et al. in press — — diet DR (0.5% glucose) AL (2% glucose) — High osmolarity upregulates Ctt1 levels [Herbert et al. in press].
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