Table 1.

Occurrence of various phenotypes associated with cellular senescence in fibroblasts, astrocytes and neurons in normal aging, and in Alzheimer’s and Parkinson’s diseases.

Phenotype	Fibroblasts	Astrocytes	Neurons	Normal Aging	Alzheimer’s Disease	Parkinson’s Disease
Telomere shortening	+ (Bodnar et al., 1998; Harley et al., 1990)	− (Evans et al., 2003)		− (Cherif et al., 2003)	Inconclusive (Eitan et al., 2014)	Inconclusive (Eitan et al., 2014)
β-galactosidase	+ (Dimri et al., 1995)	+ (Bhat et al., 2012; Bitto et al., 2010; Evans et al., 2003)	+ (Jurk et al., 2012) (Squillaro et al., 2012) (neuroblastoma) (Wan et al., 2014)(PC12)	+ (Geng et al., 2010)	+ (Tiribuzi et al., 2011)	+ (van Dijk et al., 2013) (CSF)
Lipofuscin	+ (Sitte et al., 2001; Vogt et al., 1998)	+ (Kim et al., 2002)	+ (Panossian et al., 2011)	+ (Kim et al., 2002; Oenzil et al., 1994)	+ (Hirai et al., 2001)	+ (Braak et al., 2003)
Morphological changes	↑ cytoplasm/nucleus, flat (Wang and Gundersen, 1984)	Enlarged cell body, flat (Yamada et al., 2008)	↑ cytoplasm/nucleus (Ledda et al., 2000; Peinado et al., 1993) Dendritic atrophy and regression (Rafols et al., 1989) ↓ myelination (Peters et al., 2000)		Dendritic spine defects (Zhao et al., 2006)
Nuclear disorganization	↓ Lamin B (Freund et al., 2012; Shimi et al., 2011)	↑ Size, nuclear bodies, nucleolar disorganization (Berciano et al., 1995)	No change (Lesuisse and Martin, 2002) ↑ nuclear area/IOD (Rodrigues et al., 2014)
Cell cycle regulating genes	p53 (Kulju and Lehman, 1995) p16(INK4a) (Alcorta et al., 1996) p21WAF1 (Alcorta et al., 1996; Noda et al., 1994) E2F-1 loss (Dimri et al., 1994) Activated Rb (Narita et al., 2003)	p53, p21WAF1 (Bitto et al., 2010; Evans et al., 2003) p16(INK4a) (Bitto et al., 2010) (Bhat et al., 2012) (both in vivo and in vitro)	p16(INK4a), p21, pRb (Wan et al., 2014)	p16(INK4a) (Bhat et al., 2012)	p16(INK4a) (Bhat et al., 2012; Luth et al., 2000; McShea et al., 1997) p21RAS (Luth et al., 2000) ↑ CDK4 (McShea et al., 1997) Hyper-P Rb (inactive) (Ranganathan et al., 2001) PAK3 inh. (McPhie et al., 2003)	Hyper-P Rb (inacitve) (Jordan-Sciutto et al., 2003)
p38MAPK	+ (Freund et al., 2011; Iwasa et al., 2003)	+ (Bhat et al., 2012)	+ (Jurk et al., 2012)	− (Sun et al., 2003)	+ (Pei et al., 2001; Savage et al., 2002; Sun et al., 2003)
SASP	IL-6, IL-8, MMP-3 (Rodier et al., 2009) NF B (Freund et al., 2011)	IL-6, MMP-1 (Bhat et al., 2012) IL-1β (Yu et al., 2002)	IL-6 (Jurk et al., 2012)	MMP-1 (Bhat et al., 2012)	IL-6 (Bauer et al., 1991a; Blum-Degen et al., 1995; Huell et al., 1995; Luterman et al., 2000; Wood et al., 1993) IL-1β (CSF) (Blum-Degen et al., 1995) TGF-β (Luterman et al., 2000) MMP-1 (Bhat et al., 2012)	IL-6, IL-1β (Blum-Degen et al., 1995) (CSF)
SAHF	+ (Bitto et al., 2010; Narita et al., 2003)	+ (Bitto et al., 2010)
Retrotransposons	↑ Alu, SVA, L1 (De Cecco et al., 2013)			↑ R1, R2, gypsy (Li et al., 2013)
DNA methylation	Global hypomethylation, ↓ DNMT1, ↑MBD2 (Zhang et al., 2008)				↓ DNMT1, MBD2 (Mastroeni et al., 2010)
Histone modifications	SIRT6, H3K9 (Michishita et al., 2008) H3K9me3, H3K27me3 (Chandra et al., 2012)		γH2AX (Jurk et al., 2012) (Wan et al., 2014) (PC12) ↓ SIRT1 (Panossian et al., 2011) ↓ heterochromatic areas, ↓ H3K9me3, ↑ H3K9Ac (Rodrigues et al., 2014)		↓ euchromatin fraction (Crapper et al., 1979)
Autophagy-lysosomal dysfunction	↓ Atg7, Atg12, Lamp2 (Kang et al., 2011)			↓ autophagy (Lipinski et al., 2010)	↑ autophagy, ↓ lysosomal degradation (Lipinski et al., 2010) ↓ membrane impermeability (Yang et al., 1998) ↑ autopha-gosomes (Lee et al., 2010)	↓ LAMP1, Cathepsin D, HSP73 (Chu et al., 2009) ↓ Cathepsin E ↑ α-fucosidase (van Dijk et al., 2013) (CSF)
Mitochondrial dysfunction	↑ MtDNA damage (Chen et al., 1995)	↑ ROS production (Pertusa et al., 2007) ↓MMP (Lin et al., 2007)	↑ ROS production (Jurk et al., 2012) (Wan et al., 2014) (PC12, SH-SY5Y)) ↑ mitochondrial size (Martinelli et al., 2006)	↑ MtDNA (Mecocci et al., 1993) ↓ α-subunit F1 ATP synthase (Lu et al., 2004)	↑ MtDNA damage, Enlarged morphology, ↓MMP (Trimmer et al., 2000) ↑ ROS production, ↓ Complex IV activity (Sheehan et al., 1997a) ↓ Drp1, OPA1, Mfn1, Mfn2 ↑ Fis1 (Wang et al., 2009)	↑ MtDNA Damage, Enlarged morphology, ↓MMP (Trimmer et al., 2000) ↓ Complex I activity (Sheehan et al., 1997b) Mut DJ-1, PINK1, Parkin1 (Bonifati, 2014)