|H2S ||Hydrogen Sulfide ||Hydrogen sulfide (H2S) is a colorless, poisonousness, flammable gas with the characteristic foul odor of rotten eggs. A few breath of air containing high levels H2S can cause death, while lower long-term exposure can cause eye irritation, headache, and fatigue.
The human body produces small amounts of hydrogen sulfide and uses it as signaling molecule. It has a variety of physiological effects. For instance, it relaxes the vascular endothelium and smooth muscle cells, which is important to maintaining clean arteries as one ages. It is an important signaling molecule because of its significant effects on the cardiovascular and nervous systems.
Hydrogen sulfide appears to slow aging by inhibiting free-radical reactions via the activation of SIRT1 and probably through its Interactions with Klotho.
Klotho seems to be upregulated by hydrogen sulfide and extends lifespan via a number of different pathways, some of which promote production of endogenous antioxidants.
H2S produced in the kidneys has direct angiotension-converting enzyme (ACE) inhibiting activity. It is therefore an ACE inhibitor, just like certain drugs that mitigate high blood pressure.
Plasma hydrogen sulfide declines with age and is lower in spontaneously hypertensive rats. A lack of hydrogen peroxide is in general implicated in cardiovascular disease. Declining hydrogen sulfide levels also underline neurological health. Endogenous hydrogen sulfide is lower in animal model of Parkinson disease and depressed in the brains of patients with Alzheimer's disease. Hydrogen sulfide may also protective in animal models as well as humans against cancer . ||— |
|Fhos ||— ||Fhos exhibits a coding region difference unique to animals under experimental evolution selected for longevity .
Fhos is upregulated under microbial infection  and downregulated with age . ||Fruit fly |
|Tequila ||— ||Tequila exhibits a coding region difference unique to animals under experimental evolution selected for longevity .
Tequila is upregulated with age and microbial infection, while downregulated with oxidative stress [11095759; 17196240; 15475297].
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|mir-277 ||— ||Constitutive miR-277 expression shortens lifespan and synthetically lethal with reduced insulin signaling, indicating that metabolic control underlies this phenotype. Transgenic inhibition with a miRNA sponge construct also shortens lifespan .
miR-277 is downregulated during adult life .
mir-277 controls branched-chain amino acid catabolism and as a result it can modulate the activity of TOR kinase . ||Fruit fly |
|Pdf ||Pigment-dispersing factor ||Pdf declines with aging. Age-dependent Pdf decline is responsible for the circadian rhythm attenuation .
Overexpression of Pdf suppresses age-associated changes in the period and strength of free-running locomotor rhythms and amplifies TIM oscillations in many pacemaker neurons in the elder flies .
Age-associated reduction of Pdf may cause attenuation of intercellular communication in the circadian neuronal network and of TIM cycling, which may result in the age-related rhythm decay .
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|tim ||timeless ||TIMELESS (TIM) oscillation are attenuated in the cerebral clock neurons of elderly flies .
Tim01 mutants have nearly a 50% reduced fecundity . ||Fruit fly |
|SST ||Somastatin ||Two with age-related differential methylation markers lay within Somastatin (SST)  which declines with age and is linked to Alzheimer's disease . ||Human |
|CCL11 ||chemokine (C-C motif) ligand 11 ||CCL11 exhibits an age-related increase in the plasma and cerebrospinal fluid from healthy human individuals between 20 and 90 years . ||Human |
|CCL2 ||chemokine (C-C motif) ligand 2 ||CCL2 levels in plasma increase with age and it is part of the senescence-associated secretory phenotype . ||Human |
|Cisd2 ||CDGSH iron sulfur domain 2 ||Cisd2 knockouts expire premature ageing and reduced lifespan . A persistent level of Cisd2 achieved by transgenic expression extends mean, median and maximum lifespan without any apparent deleterious side effects . ||House mouse |
|CCL11 ||chemokine (C-C motif) ligand 11 ||CCL11 is an age-related systemic factor associated with decreased neurogenesis. Relative levels of CCL11 increase in the plasma during aging an in young mice during Heterochronic Parabiosis . ||House mouse |
|CCL2 ||chemokine (C-C motif) ligand 2 ||CCL2 levels are evaluated in old unpaired and young heterochronic (with old animals) paired mice . ||House mouse |
|Bub1b ||budding uninhibited by benzimidazoles 1 homolog, beta (S. cerevisiae) ||Bub1b hypomorphic mutation decreases median lifespan by 60% (from 15 to 6 months) and such mutant mice that procude low levels of the protein are prone to aneuplody and develop many phenotypes suggestive of accelerated aging, including short lifespan, growth retardation, sarcopenia, lordokyphosis, progressive bilateral cataracts, substantial loss of sub dermal adipose tissue, spinal kyphosis, muscle atrophy, reduced dermal thickness and decreased wound healing [15208629; 17272762; 16781018; 18516091].
Moreover, there is a pronounced increase in senescent associated Beta-galactosidase expression in late generation Bub1b mutant mice, indicative of increased rate of cellular senescence. Homozyogous knockout of Bub1b results in lethality, while heterozygous animals exhibit no aging phenotypes .
Sustained high-level expression of BubR1 preserves genomic integrity and reduces tumorgenesis (even in the presence of genetic alterations that strongly promote aneuplodization and cancer, such as oncogenic Ras) and extends the lifespan and delays age-related deterioriation and aneuploidy in several tissues .
BubR1 overabundance exerts its protective effect by correcting mitotic checkpoints defects .
BubR1 expression level declines with age in various tissues [15208629; 17272762; 16781018].
The median and maximum lifespan of mice with a nonsense mutation 2211insGTTA in BubR1 is significantly reduced. BubR1(+/GTTA) mice develop several aging-related phenotypes at an accelerated rate, including catarct formation, lordokyphosis, skeletal muscle wasting, impaired exercise ability, and fat loss. Further BubR1(+/GTTA) mice develop mild anaplodies and exhibit enhanced growth of carcinogen-induced tumors [Wijshake et al. 2012].
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|Cdkn2a ||cyclin-dependent kinase inhibitor 2A ||Cdkn2a encodes different transcripts involved mostly in cell cycle regulation and cellular senescence , but it can also act as a tumor suppressor. Its expression level increase with age in rodents . super-Ink4a/Arf mice carrying a transgenic copy of a large genomic segment containing an intact and complete copy of the Cdkn2a (a.k.a. Ink4a/Arf) gene are significantly protected from cancer and had no indication of accelerated aging. Cells derived from super-Ink4a/Arf mice have increased resistance to in vitro immortalization and oncogenic transformation . Loss of Cdkn2a in mice results in tumour susceptibility . Mice deficient in Cdkn2a have smaller age-related decline in self-renewal potential as this process is associated with increasing levels of Cdkn2a .
Increased levels of p16 are associated with aging (Krishnamurthy et al., 2006; Molofsky et al., 2006) and a bona fide marker of cellular senescence (Collado et al., 2007). p16INK4a accumulates in many tissues as a function of advancing age (Krishnamurthy et al., 2004; Nielsen et al., 1999; Zindy et al., 1997) and is an effector of senescence (Campisi, 2003; Park et al., 2004),
p16INK4a is a potent inhibitor of proliferative kinase Cdk4 (Lowe and Sherr, 2003) which is essential for pancreatic ?-cell proliferation in adult mammals (Rane et al., 1999; Tsutsui et al., 1999). p16INK4a constrains islet proliferation and regeneration in an age-dependent manner. Expression of the p16INK4a transcript is enriched in purified islets compared with the exocrine pancreas and islet-specific expression of p16INK4a increases markedly with aging (Krishnamurthy et al., 2006).
Aging in mammals is associated with reduced regenerative capacity in tissues that contain stem cells (Chien and Karsenty, 2005) which is probably partially caused by senescence of progenitors with age (Campisi, 2005; Lombard et al., 2005).
Progenitor proliferation in subventricular zone and neurogenesis in the olfactory bulb as well as multipotent progenitor frequency and self-renewal potential, all decline with ageing the mouse forebrain. The decline in progenitor frequency and function correlate with increased expression of p16INK4a (Molofsky et al., 2006).
Aging p16INK4a-deficient mice exhibit a significantly smaller decline in subventricular zone proliferation, olfactory bulb neurogenesis and the frequency and self-renewal potential of multipotent progenitors (Molofsky et al., 2006).
p16 expression in skin cells is significantly lower the the group that has a strong family history of longevity. As such a younger biological age associates with lower levels of p16INKfa positive cells .
p16 expression increases exponentially with age. Expression of p16INK4a with age does not predict cancer development. p16INK4a activation is a characteristic of all emerging cancers [http://denigma.de/url/3n].
||House mouse |