Intervertebral disc degeneration and aging: Shared molecular mechanisms and therapeutic interventions

Table 1 Representative intervention strategies targeting intervertebral disc degeneration and aging

Classification	Medicine	Effect	Signal pathway	Evidence type	Ref.
Anti-oxidative stress and mitochondrial protection	Curcumin	Anti-inflammatory; reduces oxidative damage; mitochondrial protection	MAPK	Cell; animal	[49-51]
	Resveratrol	Modulates mitochondrial function, ROS generation, and cellular energy metabolism; prevents loss of ΔΨm; preserves intracellular ATP; reduces OS-induced apoptosis; promotes matrix biosynthesis	PI3K/Akt	Cell	[52-55]
	Naringin	Anti-apoptotic; mitochondrial protection	PI3K/Akt	Cell	[57,58]
	Epigallocatechin-3-gallate	Protects ΔΨm; promote cell survival		Cell	[59]
	Kinsenoside	Inhibits NP cell senescence and mitochondrial dysfunction; enhances antioxidant capacity	AKT-ERK1/2-Nrf2	Cell; animal	[60]
	Apigenin	Protects NP cells from senescence		Cell	[61]
	HSP70	Alleviates oxidative stress-induced senescence in NP cells	JNK/c-Jun	Cell	[63]
	PGA-Mn-TP04	Restores mitochondrial function by modulating mitochondrial dynamics; improves NP cell survival; preserves disc height and NP hydration		Cell; animal	[64]
	Honokiol	Suppresses apoptosis-related proteins, oxidative stress markers, inflammatory mediators, and ECM-degrading enzymes; promotes ECM anabolic protein expression	NF-κB/JNK	Cell	[65]
Redox modulators and mitochondria-targeted antioxidants	PQQ, fullerene, fullerol	Reduce ROS-related damage; protect disc cells from oxidative injury; fullerol promotes matrix synthesis		Cell; animal	[67-72]
	Glutathione	Reduce ROS		Cell	[69]
	Estrogen	Alleviates IVDD partly by modulating antioxidant enzymes and autophagy-related pathways		Animal	[73,74]
	MitoQ	Regulate mitochondrial dynamics	Nrf2	Cell; Animal	[75]
	MitoTEMPO	Mitigates mitochondrial ROS accumulation, inflammatory activation, and mitochondrial dysfunction		Cell	[26]
	SkQ1	Anti-apoptotic; restores ΔΨm and reduces ROS levels		Cell	[77]
	XJB-5-131	Restore disc structure		Animal	[78]
Mitophagy regulation	Urolithin A	Promote mitophagy	AMPK	Cell; animal	[83]
Anti-inflammatory therapy	Higenamine	Inhibition of NF-κB pathway activation and aging of NP cells	NF-κB	Cell	[94]
	Omentin-1	Alleviate NP cell senescence, reduce G1 phase cell cycle arrest, and enhance ECM synthesis		Cell	[95]
	Dehydrocostus lactone	Reduce inflammation and ECM degradation	NF-κB; MAPK; STING-TBK1/NF-κB	Cell; animal	[96]
Senolytic therapy	O-vanillin	Reduces senescent cell burden and improves matrix synthesis		Human disc cells/tissues	[101]
	Dasatinib + quercetin	Remove senescent cells		Animal	[99,100]

PQQ: Pyrroloquinoline quinone; IVDD: Intervertebral disc degeneration; NP: Nucleus pulposus; ECM: Extracellular matrix; ROS: Reactive oxygen species; OS: Oxidative stress; ATP: Adenosine triphosphate; ΔΨm: Mitochondrial membrane potential.