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:
| ID | name | taxid | reference | pmid | tissue | comparision | start | stop | gender | description |
|---|---|---|---|---|---|---|---|---|---|---|
| 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]. |
| 90 | Accumulation of DNA damage | 10090 | — | — | — | age | — | — | — | DNA damage accumulates with age in mouse hematopoietic stem cells [32 in Lauri et al. 2012]. |
| 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]. |
| 96 | Loss of histone proteins from the genome | 4932 | — | 20832724 | — | age | — | — | — | Normal aging is accompanied by a profound loss of histone proteins from the genome [20832724]. |
| 97 | Diminished cognitive skills | 9606 | — | — | — | age | — | — | — | Cognitive skill such as learning and memory diminish with age [http://www.sciencedaily.com/releases/2012/06/120629211902.htm]. |
| 103 | Decreased stem cell activity | — | — | 20504968 | — | age | — | — | — | Advanced age is associated with decreased stem cell activity [20504968]. |
| 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. |
| 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]. |
| 60 | Protein aggregation | 6239 | — | 22103665 | whole body | age | 1 day | 11 day | hermaphrodites | protein aggreation accumulate in aged animals. Hundrets of protein are enriched in an SDS-insoluble fraction in aged nematode adn alre largely absent from similiar protein fraction in young nematodes. Genes encoding proteins that become insoluble with age are enriched for modifiers of lifespan [22103665]. |
| 61 | Loss of protein homeostasis | 6239 | — | 22103665 | whole body | — | 1 day | 11 day | hermaphrodites | Loss in protein homeostasis during aging may lead to impaird protein solubility and cellular dysfunction [22103665]. |
| 53 | DHEA increases | 9606 | Hinson and Raven, 1999 | 10495400 | serum | age | 10 year | 20 year | males/females | DHEA reaches its highest levels at age 20-24 [10495400]. |
| 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]. |
| 59 | Deteriorarition of circadian rhytms | 10090 | Farajnia, et al 2012 | — | Suprachiasmatic Nucleus | age | 2 month | 30 month | — | Aged mice have disrupted sleep hevaiour and weakened brain network activity in the SCN. Aged SCN neurons lack day-night rhythms in some membrane properties. There is an age-related reductions of certain potassium currents that are import to the neuronâs rhythmic firing. Behavioral and sleep-wake rhythms exhibit a strong fragmentation, starting at the age of 700 d. Aged mice are deficient in membrane properties and GABAergic postsynaptic current amplitude. Aging mice selectively loss circadian modulation of fast-delayed-rectifer and A-type K+ currents. In aged mice at the tissue level, the phase synchrony of SCN neurons was grossly disturbed, with some subpopulations peaking in anti-phase and a reduction in amplitude of the overall multiunit activity rhythm. |
| 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]. |
| 57 | White matter integrity decreases | 9606 | Samanez-Larkin et al., 2012 | 22496578 | white matter | age | 21 year | 85 year | males/females | Older age is associated with decreased reward learning and decreased white matter integrity in specific pathways running form the thalamus to the medial prefrontal cortex and from the meial prefrontal cortex to the ventral stratium |
| 52 | DHEA decreases | 9606 | Hinson and Raven, 1999 | 10495400 | serum | age | 25 year | 85 year | males/females | DHEAS (Dehydroepiandrosterone sulphate) is the most abundant circulating steroid secreted by adrenal glands. Duo to its position int the steroid cascade DHEA act like kind of âthe mother steroidâ (Regelson et al., 1994). DHEA reaches its highest levels at age 20-24. Its serum concentration declines with increasing age after 25 years and diminishes about 95% by 85 years. DHEA deficiency syndrome is a new term for old age [10495400]. |
| 87 | LysoPC(16:1) decrease | 10090 | — | 22661299 | — | — | 3 months | 12 momths | — | Plasma levels of LysoPC(16:1) decreases with age from 3 to 22 months [22661299]. |
| 91 | LysoPC(18:4) decrease | 10090 | — | 22661299 | serum | age | 3 months | 22 months | female | Serum levels of LysoPC(18:4) decrease from 3 to 22 months [22661299]. |
| 92 | SM(d18:1/12:0) decrease | 10090 | — | 22661299 | serum | age | 3 months | 22 months | female | Serum levels of SM(d18:1/12:0) decreasefrom 3 to 22 months [22661299]. |
| 93 | Tetracosahexaenoic acid decrease | 10090 | — | 22661299 | serum | age | 3 months | 22 months | female | Serum levels of Tetracosahexaenoic acid decrease from 3 to 22 months [22661299]. |
| 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]. |
| 3 | HDL decreases | 10090 | Wijeyesekera et al., 2012 | 22225495 | Plasma | Diet | 30% DR for 48h at 16 weeks | — | male | — |
| 6 | VLDL decreases | 10090 | Wijeyesekera et al., 2012 | 22225495 | Plasma | Diet | 30% DR for 48h at 16 weeks | — | male | — |
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