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
46 DHEA declines 9606 Jeff 70 male
50 Vitamin D3 declines 9606 As one gets odler te ability for one's skin to create Vitamin D3 declines dramatically.
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].
74 Reduced regenerative capacity Aging in mammals is associated with reduced regenerative capacity in tissues that contain stem cells [15734685;11919569].
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].
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].
88 Structural chromosome variation 9606 Acquired differences in structural chromosome variants between members of monozygoutic twin pairs (including mosaic anomalis) are observed in pairs of >55 years of age but not in younger [29 in Laurie et al. 2012].
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.
1 ROS production increases 4932 Laun et al., 2001 11251834 Age young old
2 Downregulation of exo-3 6239 Schlotterer et al., 2010 20346071 Whole body Age
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.
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].
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].
43 Follicle stimulating hormone increases 9606 Jeff Age 40 year male and emale Follicle stimulating hormone increases dramatically and becomes much more bioactive after the age of 40 in both men and women.
44 Luteneinzing hormone increases 9606 Jeff Age 40 year male and female Luteneizing hormone increases dramatically and becomes much more bioactive after the age 40 in both mena nd women.
45 human chorionic gonadotrophin increases 9606 Jeff Age 40 year male and female human chorionic gonadotrophin hCG increases in both men and women after age 40.
47 Melatonin declines 9606 Age 70/35 year male/female Melatonin peaks at night and peaks keeps dropping throughout your life and can drop by 60% by the time an individual reaches age 50. Increased age is associated with a reduction in noctronal melatonin vlaues. This drop correlates with reduction in the TAS of the blood (From Benot et al (123)).
48 Growth hormone declines 9606 Age 70/35 year male/female
49 Progesterone declines 9606 Age 70/35 year male/female
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 ”the mother steroid” (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].
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].
54 DHEA decreases 9544 Lane et al., 1997 9215277 serum Age 5 year 26 year males/females Males and female rhesus monkeys exhibit a steady, age-related decline in serum DHEAS. The proportional age-related loss of DHEAS in rhesus moneys is over twice the rate of decline observed in humans [9215277].
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
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].
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