TABLE 3.

Drugs in preclinical development, supplements or other therapies that increase Klotho.

Category (name)	Target diseases	References
y-aminobutyric acid receptor agonist (GABA)	Preclinical diabetes models, streptozotocin organ injury	Liu W, et al. (2021)
		Prud’homme et al. (2017a)
		Son et al. (2019)
		Wang Q, et al. (2019)
Recombinant protein (s-Klotho, Klotho peptide, KL1)	Preclinical diabetic, metabolic, renal, vascular, neurodegenerative, neoplastic and other diseases	Ali et al. (2020)
		Chen TH, et al. (2013)
		Doi et al. (2011)
		Gupta et al. (2022)
		Hu et al. (2017)
		Leon et al. (2017)
		Maltese et al. (2017)
		Mencke et al. (2017)
		Myung et al. (2022)
		Oh et al. (2018)
		Prud’homme et al. (2020)
		Rao Z, et al. (2019)
		Takenaka et al. (2018); Takenaka et al. (2019); Takenaka et al. (2020)
		Yang et al. (2015)
		Yuan et al. (2022)
Gene therapy and cell therapy (Klotho gene)	Preclinical, multiple diseases (alternative to recombinant protein therapy)	Arbel Rubinstein et al. (2021)
		Franco et al. (2021)
		Lin and Sun. (2015a); Lin and Sun. (2015b)
		Ni et al. (2021)
		Mencke et al. (2017)
		Shin et al. (2019)
		Xiang et al. (2021)
		Zeng et al. (2019)
Food/diet components, supplements and traditional medicines (astaxanthin, baicalin, cordycepin, curcumin, ginseng, ligustilide, resveratrol, tetrahydroxystilbene glucoside)	Multiple indications, geroprotective	Dehghani et al. (2019)
		Feng & Huang, (2022)
		Hsu et al. (2014)
		Kamel et al. (2022)
		Long et al. (2018)
		Li SS, et al. (2018)
		Lim SW, et al. (2019)
		Long et al. (2018)
		Ostojic & Engeset, (2021)
		Zhang P, et al. (2016)
		Zhang XT, et al. (2020)
		Zhou et al. (2015)