. 2015 Apr 2;11(6):867–880. doi: 10.1080/15548627.2015.1034410

Table 1.

Effects of modulation of autophagy-related and lysosomal genes on life span including in conserved longevity paradigms.

ORGANISM	GENES	FUNCTION IN STEP	LIFE SPAN OF OE¹	ROLES IN LONGEVITY PARADIGM²	TRANSCRIPTION FACTOR³
Yeast	ATG1	Autophagy initiation		Rapa ↓^§29
	ATG11	Phagophore formation		Rapa ↓^§29
	ATG7	AP^ elongation		Rapa ↓^§29, MetR ↓^§34, Sper ↓^§129
	ATG8	AP elongation		MetR ↓^§34
	ATG5	Conjugated protein of Atg12		MetR ↓^§34
	ATG8	AP elongation		MetR ↓^§34
	VAM3	SNARE protein, fusion		DR ↓^§33
	VAM7	SNARE protein, fusion		DR ↓^§33
	ATG15	Putative lipase required for intravacuolar disintegration of autophagic bodies		DR ↓^§33
*C. elegans*	unc-51/ ATG1/Ulk1	Autophagy initiation		LET-363/MTOR ↓^§§§30, DR ↓^§§30, GL ↓^§§§70, Mit ↓^§§30	PHA-4/FOXA^{70, 96}
	bec-1/ VPS30/ Becn1	Membrane nucleation		LET-363/MTOR ↓^§§§31, DR ↓^{§§30, §§§31, §§§§35} IIS ↓^{§§31, §§§§166, §§§§§167}, GL ↓^§§70 Mit ↓^{§§30, §§§§64}, Resv ↓^§§§115, Sper ↓^§§§129, miR-34 ↓^§§§146, CaN ↓^{§§§§§§ 170}	PHA-4/FOXA^{70, 96}
	vps-34/VPS34/Pik3c3	Membrane nucleation		LET-363/MTOR ↓^§§§31, DR ↓^§§§31 GL ↓^§§§70, Mit ↓^§§§§64
	atg-9	Phagophore formation		miR-34 ↓^§§§146
	atg-18/ Wipi4	Phagophore formation		GL ↓^§§§70, Mit ↓^{§§30, §§§§64}, RSKS-1/RPS6KB↓^§§§64	HLH-30/TFEB^{64, 168}
	atg-4.1	AP elongation		miR-34 ↓^§§§146
	atg-7	AP elongation		DR ↓^§§§§35, IIS ↓^{§§§31, §§§§166}, CaN ↓^{§§§§§§ 17}
	atg-12	Ubiquitin-like modifier		IIS ↓^{§§§31, §§§§166}
	lgg-1/ ATG8/Lc3	AP elongation	NE^31,Unp.	GL ↓^§§§70, Mit ↓^§§§§64	PHA-4/FOXA^{70, 96}
	vha-16	Vacuolar pH		GL ↓^§§§64	HLH-30/TFEB⁶⁴
	lmp-1	Lysosomal membrane		GL ↓^§§§64	HLH-30/TFEB⁶⁴
	C08H9.1^#	Lysosomal degradation		IIS ↓^§§§94	DAF-16/FOXO⁹⁴
	lipl-1	Lysosomal lipolysis	↑⁶⁷		HLH-30/TFEB⁶⁷
	lipl-3	Lysosomal lipolysis	↑⁶⁷		HLH-30/TFEB⁶⁷
	lipl-4	Lysosomal lipolysis	↑⁶⁹	GL↓ ^§§§69, IIS ↓^§§§69	DAF-16/FOXO⁶⁹
*Drosophila*	Atg1/Ulk1	Autophagy initiation	↑^¶,¶¶39	AMPK ↓^¶,§§§39	dFOXO/Foxo?³⁹
	Atg7*	AP elongation		Sper ↓^§§129
	Atg5	AP elongation		Rapa ↓^§§§§§32
	Atg8/Lc3	AP elongation	↑^¶37
Mouse	Atg5	AP elongation	↑³⁶

(1) Life span of animals overexpressing (OE) autophagy gene: NE, no effect; ↓, decreased; ↑, increased. Note that most autophagy deletion mutants are short lived, likely due to developmental defects.

(2) Effect of autophagy gene inactivation on conserved longevity models: AMPK, overexpression of PRKAA/α-subunit of AMPK; CaN, reduced calcineurin signaling; DR, dietary/caloric restriction; GL, germline removal; IIS, reduced INS/insulin-IGF1 signaling; MetR, methionine restriction; miR-34, miR-34 loss of function; Mit, reduced mitochondrial respiration; Rapa, rapamycin treatment; Resv, resveratrol treatment, Sper, spermidine treatment; LET-363/MTOR, reduced TOR signaling.

(3) Transcriptional regulation of autophagy gene by noted transcription factor in at least 1 longevity model (not specified).

^AP, autophagosome.

*, known epigenetic regulation.

§, chronological life span was assessed.

§§, genetic mutant used. Genetic mutation of autophagy genes shortens somewhat the life span of wild-type C. elegans.

§§§, adult-only RNAi treatment. This treatment generally does not shorten the life span of wild-type C. elegans.

§§§§, RNAi treatment from L4 stage. This treatment generally does not shorten the life span of wild-type C. elegans.

§§§§§, whole-life RNAi treatment. This treatment generally shortens somewhat the life span of wild-type C. elegans.

§§§§§§, RNAi treatment for 2-4 generations

#, C08H9.1 is a putative lysosomal serine carboxypeptidase/CTSA homolog, i.e., C08H9.1.

¶, overexpression from neuron-specific promoter.

¶¶, overexpression from intestinal promoter.

Unp., unpublished by Hansen lab.