|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 |
|Gdf11 ||growth differentiation factor 11 ||GDF11 is a circulating factor in young mice that declines with age.
Treatment of old mice to restore GDF11 to youthful levels recapitulated the of young-old parabiosis and reverses age-related hypertrophy. ||House mouse |
|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 . ||— |
|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 .
||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 |
|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 |
|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 |
|Mnt ||CG13316-PC, isoform C ||A dMnt null allele results in flies with larger cells, increased weight, and decreased lifespan . ||Fruit fly |
|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].
||House mouse |