lifespan

Parishin (Parishin A) A is isolated from the rhizomes of Gastrodia elata. It has good neuroprotective effects against brain disorders.

Cyclogalegenin (Astramembrangenin) is able to elongate telomeres, resulting in increased lifespan of the animals.

2-O-(α-D-Glucopyranosyl)glycerol (2-alphaGG) is present in certain bacteria and plants that thrive in harsh environments and may extend the lifespan of budding yeast and erythrosporidium by enhancing their osmotic response.

Qingyangshengenin B (Otophylloside B) is a C-21 steroidal glycoside isolated from Qingyangshen. Qingyangshengenin B protects against Aβ toxicity, which decreases Aβ deposition by decreasing the expression of Aβ at the mRNA level. Qingyangshengenin B has antiepileptic and anti-aging effects, it can extend lifespan, increase heat stress-resistance, delay body paralysis, and increase the chemotaxis response in C. elegans models of Alzheimer's disease. Otophylloside B can suppress the seizure-like locomotor activity caused by pentylenetetrazole in zebrafish.

Benzyl-piperazine-CO-benzothiazole-4-methylpiperidine can be used to alter the lifespan of eukaryotic cells.

WAY-326766 increases ion transport through mutant CFTR and can be used to alter the lifespan of eukaryotes.WAY-326766 can be used to treat cystic fibrosis (CF).

WAY-620472 is a PPAR regulator that can be used to alter the lifespan of eukaryotes.

HPN-01 (IKK inhibitor XII) is a selective IKK inhibitor that inhibits IKK-α, IKK-β, and IKK-ε. HPN-01 reduces the severity of the disease, attenuates the immune imbalance, and prolongs the lifespan of mice in a model of autoimmune encephalomyelitis, and can be used to study immune disorders.

KBU2046 is an orally administered compound that inhibits cell motility and invasion, effectively suppressing cancer metastasis and extending lifespan. This compound uniquely targets and binds to chaperone heterocomplexes, selectively modifying the interaction of client proteins involved in motility regulation, while avoiding the characteristics typical of classical HSP90 inhibitors.

CXM102 is an activator of autophagy. This compound induces autophagy in aged BMSCs, rejuvenating them and promoting their preferential differentiation into osteoblasts. CXM102 enhances the nuclear translocation of transcription factor EB (TFEB) and the formation of osteoblasts. In middle-aged male mice, it stimulates bone anabolic metabolism, reduces marrow adipocytes, delays bone loss, lowers serum inflammation levels, reduces organ fibrosis, and extends lifespan.

Fluopimomide (LH2010A), a powerful insecticide, is extensively utilized in the control of agricultural pests. It adversely affects the growth, locomotor behavior, reproduction, and lifespan of nematodes. Concurrently, it leads to increased production of reactive oxygen species (ROS), accumulation of lipids and lipofuscins, as well as a rise in malondialdehyde content. Additionally, Fluopimomide inhibits the antioxidant system of nematodes.

SKQ1, also known as Visomitin or plastoquinonyl decyltriphenyl phosphonium (PDTP), is a potent mitochondrial-targeted antioxidant. As the active pharmaceutical ingredient (API) in Visomitin eye drops, SKQ1 exhibits various biomedical activities: (1) prevents impairment of long-term potentiation in rat hippocampal slices caused by amyloid β-protein; (2) reverses aging-related biomarkers in rats; (3) slows age-related degenerative changes in the retinas and choroid of Wistar and OXYS rats; (4) extends the lifespan of male rodents in LP or SPF conditions. SKQ1 can penetrate cell membranes and is proposed for use in anti-aging therapies. Clinical trials for SKQ1 are currently underway in Russia to treat glaucoma. For convenience, SKQ1 is provided as an ethanol-water (1:1, v/v) solution at a concentration of 200 mg/mL.

AKV-9 is a mutant Cu/Zn superoxide dismutase (SOD1) inhibitor that effectively suppresses SOD1-induced protein aggregation and demonstrates significant protective effects against SOD1-induced cytotoxicity in PC-12 cells, with an EC50 of 0.3 μM. AKV-9 also ameliorates amyotrophic lateral sclerosis (ALS)-related phenotypes and significantly prolongs survival in mouse models, making it suitable for ALS pathogenesis and targeted therapy research.

TERT activator-2 (Compound 1030) is an activator of telomerase reverse transcriptase (TERT), which enhances the expression levels of TERT within cells. TERT activator-2 is applicable to research related to cellular lifespan and telomere functions.

HSP90α-IN-1 is an HSP90α inhibitor (IC50= 111 nM) that demonstrates anti-aging activity across various cellular senescence models. Belonging to the xanthine family, HSP90α-IN-1 is involved in research focused on combating age-related inflammation, senescence, and diseases (including cancer), and it may contribute to extending healthy lifespan.

PSEC13 is an activator of the HSF-1/DAF-16 axis. It upregulates heat shock proteins and can form hydrogen bonds with key residues at the active site of HSP-16.2. By regulating HSP-16.2, PSEC13 enhances protein homeostasis and extends lifespan. It also promotes the nuclear translocation of daf-16, increasing the proportion of intermediates. PSEC13 is applicable for research on aging and age-related diseases.

KIT-13 is an orally active acetal phospholipid derivative that effectively inhibits neuroinflammation and addresses mitochondrial DNA leakage issues associated with Mecp2 deficiency. It significantly alleviates neurological symptoms and prolongs lifespan in Rett Syndrome (RTT) model mice. KIT-13 is valuable for research in RTT and other neuroinflammation-related conditions.

ALR2-IN-9 is a potent inhibitor of ALR2 with an IC50 of 21.8 nM, demonstrating excellent antioxidant activity with an EC50 of 2.8 μM in DPPH free radical scavenging. It directly interacts with reactive oxygen (ROS) and reactive nitrogen species (RNS), blocking free radical chain reactions, and acts as an endogenous enzyme antioxidant regulator to modulate catalase (CAT) and superoxide dismutase (SOD) enzyme functions. By influencing the PI3K/Akt/Nrf2 pathway, ALR2-IN-9 inhibits excessive mitochondrial superoxide production induced by hyperglycemia in vitro and ameliorates oxidative stress induced by CuSO4 and H2O2 in vivo models. The compound also extends the lifespan of *Caenorhabditis elegans* by regulating stress response genes such as PMK-1 and shows potential as an anti-aging candidate. ALR2-IN-9 can be utilized in diabetes complication research.

FP802 is a potent oral TwinF interface inhibitor capable of disrupting and neutralizing the toxicity of the NMDAR/TRPM4 death complex. Within the 5xFAD Alzheimer's disease (AD) mouse model, FP802 demonstrates significant neuroprotective effects, preventing cognitive decline, preserving neuronal structural integrity, reducing β-amyloid plaque formation, and mitigating mitochondrial damage. In the amyotrophic lateral sclerosis (ALS) mouse model, FP802 prevents motor neuron loss, lowers serum neurofilament light chain (NfL) levels, improves motor performance, and extends the lifespan of mice. FP802 can be utilized for research related to Alzheimer's disease and amyotrophic lateral sclerosis [1][2].

Sulfamethylthiazole is an orally active derivative of Sulfanilamide. It exhibits nearly equivalent efficacy to Sulfathiazole in prolonging the lifespan of mice infected with Staphylococcus aureus.

Valeroyl Salicylate (2-Valeryloxybenzoic acid) has anti-inflammatory properties that extend lifespan, delay the age-related decline in spontaneous activity, and improve stress tolerance.

GW8510 is a CDK2 (cell cycle protein-dependent kinase 2) inhibitor and RRM2 (Ribonucleotide Reductase Regulatory Subunit M2) inhibitor that affects DNA synthesis and antiproliferation in tumor cells. In mammalian aging models, GW851 improves cognition and prolongs lifespan, which may be related to the modulation of the expression of cell cycle-related protein p21 and CDK family genes, as well as the improvement of mitochondrial function.

Promotes proteasomal degradation of Miro1 (mitochondrial Rho GTPase 1). Reduces Miro1 levels in fibroblasts from Parkinson's disease (PD) patients (IC50 = 7.8 μM). Exhibits no significant effect on related outer mitochondrial membrane protein Mitofusin. Reduces stress-induced degeneration of dopaminergic neurons derived from PD patient iPSCs. Rescues age-dependent neuronal loss and prolongs lifespan in fly PD models.

Sirtuins (SIRTs) represent a distinct class of trichostatin A-insensitive lysyl-deacetylases (class III HDACs). Human SIRT1 is the homolog of yeast silent information regulator 2 (Sir2) and has been shown to regulate the activity of the p53 tumor suppressor and inhibit apoptosis. Small molecule activators of SIRT1, such as resveratrol, extend lifespan in yeast and C. elegans in a manner that resembles caloric restriction. CAY10591 has been identified as an activator of the enzyme SIRT1. This compound increases fluorescence by 233% in a SIRT1 activity assay. [Activator activity was defined as the percentage of signal increase relative to signal window in the following formula: 100 x (Sample - Signallow)/(Signalhigh - Signallow)]. CAY10591 suppresses TNF-α in a dose-dependent manner. In THP-1 cells, TNF-α levels decreased from 325 pg/ml (control) to 104 and 53 pg/ml with 20 and 60 µM CAY10591, respectively. This activator also has a significant dose-dependent effect on fat mobilization in differentiated adipocytes, which would indicate the potential of SIRT1 activators for anti-obesity or anti-diabetic purposes.