Table 2.

Recent studies on AGE formation and impacts in tendon.

Treatment	Species/tissue	Age/time point	Analysis	Major findings	Source
Aging	Human patellar tendon	67 ± 3 years, 27 ± 2 years	Mechanical testing, collagen crosslink analysis	Aged tendons show increased HP, LP, and pentosidine crosslinks and decreased maximum force	Couppé et al, 2009
Diabetic conditions	Mouse tail tendon	26 weeks old	HPLC for crosslink analysis, mass spectrometry	AGE-mediated crosslinks interact in the same Hyl domains as enzymatic crosslinks	Hudson et al., 2018
	Human Achilles tendon	58–60 years old	Mechanical testing, TEM	Diabetic patients show increased Young’s modulus in tendon	Couppé et al., 2016
	Rat tail tendon	9–10 weeks old	Collagen solubility, Ehrlich test, fluorescence imaging	Green tea treatment decreases markers of advanced glycation and increases collagen solubility	Babu et al., 2008
High AGE diet	Rat Achilles and tail tendons	40 weeks old	Mass spectrometry, HPLC	High-AGE diet increases AGE content in Achilles and tail tendons, with Achilles having higher AGE levels than tail tendons	Skovgaard et al., 2017
Ribose	Bovine tail tendons	18–30 months old	Mechanical testing, scanning calorimetry, SEM	Ribose treatment alters nanoscale collagen fibril deformation mechanisms in tendon	Lee and Veres, 2019
	Rat tail tendon	6 months old	Fluorescence imaging, enzyme susceptibility assay, mechanical testing	Ribose-treated and mechanically loaded tendons are more susceptible to collagenase activity	Bourne et al., 2015
MGO	Rat tail tendon	3, 12, and 22 months old	Collagen solubility, SDS-PAGE, mass spectrometry	Glucosepane is the predominant AGE; MGO treatment increases tendon stability	Jost et al., 2018
	Rat tail tendon	> 17 weeks old	Mechanical testing, multiphoton imaging	MGO treatment diminishes fiber-fiber sliding and increases fiber stretch	Li et al., 2013
	Rat tail tendon	17–24 weeks old	Mechanical testing, SAXS	MGO treatment alters molecular collagen deformation mechanisms (increased fibril failure resistance and reduced molecular sliding within fibrils)	Fessel et al., 2014
Glutaraldehyde	Rat tail tendon	Adult	Nanoindentation	Glutaraldehyde treatment results in a more brittle behavior during fibril fracture	Gachon and Mesquida, 2020
Sodium borohydride	Mouse tail tendon	11 weeks old	Mechanical testing, HPLC mass spectrometry	Reduction with sodium borohydride decreases stress relaxation and plastic deformation and increases failure stress	Stammers et al., 2020