Table 1.

Strategies and studies targeting cancer cachexia and sarcopenia.

Disease	Intervention	Model	Main Findings	Reference
Cancer cachexia	Salidroside	Mice with C26 and LLC	Decreased mTORC1 in muscle	Chen et al., 2016 [97]
		C2C12 treated with TNF-⍺	Decreased mTORC1 in myotubes
	Raptor KO mice	Mice with LLC and C26	Decreased mTORC1 activity Increased autophagic flux	Geremia et al., 2022 [98]
	IL-6 receptor Ab	ApcMin/+ mice	Decreased mTORC1 activity Increased AMPK activity	White et al., 2011 [72]
	Aerobic exercise Rapamycin	C26-bearing mice and colon carcinoma patients	Loss of body weight Decreased autophagic flux	Pigna et al., 2016 [100]
	Rapamycin	C2C12 cells treated with conditioned media from C26 cells	Induced myotube atrophy Blockage of autophagic flux
	Everolimus or Temsirolimus (Rapalog)	20 patients with renal cell carcinoma or pancreatic neuroendocrine tumour	Decreased muscle quantity, muscle mass and skeletal muscle area.	Gyawali et al., 2016 [101]
	Everolimus	410 patients with advanced pancreatic neuroendocrine tumors	Loss of body weight and reduced appetite.	Yao et al., 2011 [102]
	Everolimus with endocrine therapy, aromatase inhibitor	724 female patients with ER-positive breast cancer	Decreased body weight and reduced appetite.	Baselga et al., 2012 [103]
	Everolimus	302 patients with advanced, nonfunctional, well-differentiated lung or gastrointestinal neuroendocrine tumors	Decreased appetite.	Yao et al., 2016 [104]
	Temsirolimus	162 patients with relapsed or refractory MCL		Hess et al., 2009 [105]
	Nivolumab Everolimus	821 patients with advanced clear-cell renal-cell carcinoma		Motzer et al., 2015 [106]
Sarcopenia	Rapamycin	Male mice expressing LC3-GFP	Reactivation of autophagy prevented satellite cells senescence.	Garcia-Prat et al., 2016 [80]
	Rapalog RAD001	Old Male Sprague-Dawley rats (27 months)	Increased mTORC1 activation	Joseph et al., 2019 [110]
	Exercise	21-month-old Wistar rats	Increased autophagy via downregulating mTORC1 pathway.	Zeng et al., 2020 [119]
	Calorie restriction	Middle-aged Male Sprague-Dawley rats (20 months old)	Decreased mTORC1 activity	Chen et al., 2019 [120]
	Calorie restriction and resveratrol	Male FBN 25-month-old rats	Enhanced autophagy by inhibition of mTORC1 pathway	Dutta et al., 2014 [121]
	Calorie restriction and dietary resveratrol	Middle age to old age mice (14 months old to 30 months old)	Both dietary interventions prevent aging process through mTORC1	Barger et al., 2008 [122]
	Spermidine and exercise	D-galactose-induced aging rats with skeletal muscle atrophy	Increased autophagy	Fan et al., 2017 [123]
	Spermidine	8-week-old specific pathogen-free male C57/BL mice	Induced muscle atrophy and enhanced autophagy in MuSCs.	Zhang et al., 2018 [124]
	Testosterone therapy and resistance exercise	18 aged men (Ages 65–75 years)	Improve aging muscle performance and muscle mass via mTORC1	Gharahdaghi et al., 2019 [125]