Table 1 Overview of different therapeutic agents, the individual therapeutic targets, and effects

SS-31 (elamipretide, MTP-131)

Small peptide, mitoprotectin

Mitochondria, cardiolipin

Stabilization of MIM via binding to cardiolipin; cell protection (prevents cytochrome c release);

maintenance of mitochondrial function (mitoprotection)

[142, 143]

Omaveloxolone

Nrf2 activator

Nrf2/ARE-pathway

Upregulation of antioxidant target genes, e.g., HO-1 and SOD2; cell protection (anti-apoptotic response); maintenance of tissue homeostasis

[144, 290]

Theaflavin-3,3′-digallate

Natural phenol (black tea), antioxidant

Nrf2/ARE-pathway

Upregulation of antioxidant targets, e.g., GPX4 and HO-1; prevention of ferroptosis (upregulation of FTH-1, SLC7A11, and GPX4);

maintenance of tissue homeostasis

[155]

Deferoxamine

Iron chelator

Nrf2/ARE-pathway,

HIF-1a

Upregulation of antioxidant targets, e.g., HO-1, and NQO-1;

prevention of ferroptosis (reduction of ACSL4, LOX15, P53, and LPCAT3);

stabilization of HIF-1a,

increase of osteogenic differentiation/ improvement of fracture healing

[154, 291]

Licochalcone A

Natural phenol (Glycyrrhiza roots),

antioxidant

Nrf2/ARE-pathway;

NFκB pathway

Inhibition of NFκB pathway; prevention of LPS-induced pyroptosis (reduction of NLRP3, GSDMD, caspase‐1, IL‐1β, and IL‐18); upregulation of antioxidant targets, e.g., Nrf2 and HO-1,

[176]

Pioglitazone

Antidiabetic drug (thiazolidinedione)

Nrf2/ARE-pathway, mitochondria (via PGC1-α/ Δψm pathway)

Activation of Nrf2- and PGC1-α/Δψm pathway,

Prevention of LPS/ATP-induced pyroptosis (downregulation of NLRP3, caspase-1, IL‐1β, IL‐18, and GSDMD-N); increase of mitochondrial function and biogenesis (lower ROS production)

[177]

SRT1720

SIRT1 activator

SIRT1

Activation of autophagy; maintenance of tissue homeostasis

[146, 292]

NAC

Antioxidant

ROS (as direct scavenger and precursor of glutathione)

Cell protection (prevents apoptosis and necroptosis); downregulation of redox-sensitive signaling; maintenance of tissue homeostasis

[142, 146]

Simvastatin

Statin, Senomorphic

HMG-CoA

Antioxidative properties (upregulation of SOD2, suppression of NOX2, NOX4);

increase of osteogenesis; maintenance of tissue homeostasis

[293, 294]

Resveratrol

Natural phenolic compound, Senomorphic

SIRT1

Mitochondria (mitophagy) via mTOR/AMPK pathway

Induction of antioxidant defense by HO-1 and Nrf2; reduction of iNOS and NO, induction of autophagy, suppression of NFkB signaling pathways; maintenance of tissue homeostasis

[220, 289]

Urolithin A

Natural postbiotic compound

Mitochondria (mitophagy)

Nrf2-pathway

Improvement of mitochondrial function (enhances mitophagy); induction of Nrf2 and thus antioxidative proteins; maintenance of tissue homeostasis

[217]

MDL-800

Allosteric activator of SIRT6

SIRT6

Attenuation of ROS activity and downregulation of senescence markers; maintenance of tissue homeostasis

[221]

Metformin

Antidiabetic drug (biguanide), AMPK agonist

Mitochondria/ mitophagy (via mTOR/AMPK pathway)

Reduction of ROS production and senescence; Increase of osteogenesis and autophagy; maintenance of tissue homeostasis

[23, 295]

Rapamycin (Sirolimus)

Makrolide (macrocyclic lacton)

Mitochondria/ mitophagy (via mTOR/AMPK pathway)

Increase of PINK1/Parkin-dependent mitophagy; inhibition of apoptosis; maintenance of tissue homeostasis

[282]