Natural Compounds and Aging: Between Autophagy and Inflammasome

Table 1

The impact of aging on lifespans.

The molecular hallmarks of age	Age-related changes	Reference
Genomic instability
Nuclear DNA	Chromosomal aneuploidies and copy number variations	[71–73]
Mitochondrial DNA	Replication errors cause polyclonal expansion of mtDNA mutations	[74]
Telomere exhaustion	Shortened telomeres exhibit decreased lifespans	[75, 76]
Epigenetic alterations
Histone modifications	Deficiency in SIRT6 exhibits accelerated aging	[77]
DNA methylation	Polycomb target genes become hypermethylated with age	[78]
Chromatin remodeling	HP1α effects longevity in flies	[79]
Transcriptional alterations	Micro-RNA mir-71 is required for the lifespan extension	[80]
Loss of proteostasis
Chaperone-mediated protein folding and stability	HSPs decline on longevity; Accumulation and aggregation of abnormal proteins occur in aged organism	[81, 82]
Delay or dysfunction of autophagy	mTOR signaling in the regulation of mammalian lifespan	[83]
The ubiquitin-proteasome system	Enhancement of proteasome activity extends replicative lifespan in yeast	[84]
Deregulated nutrient sensing
The insulin- and IGF-1-signaling pathway	Levels decline and dysfunction of GH/IGF-1 signaling pathway	[39, 85]
mTOR and AMPK	Inhibition of mTOR/DR pathway extends lifespan	[86, 87]
Mitochondrial dysfunction
ROS	Amphibious effects of ROS on aging	[88–91]
Mitochondrial Integrity and Biogenesis	Reduced efficiency of telomerase activation with aging	[92]
Cellular senescence
The INK4a/ARF Locus	Ink4a/ARF expression increases aging	[93, 94]
Stem cell attrition	Hematopoiesis declines with age resulting in a diminished production of adaptive immune cells; Reduced in cell-cycle activity of hematopoietic stem cells (HSCs) on aged mice	[7, 95]
Inflammation	Activation of the NLRP3 inflammasome leading to increased production of IL-1β, TNF, and interferons	[36, 96]

SIRT6: sirtuin-6; HP1α: heterochromatin protein 1α; HSPs: heat shock proteins; mTOR: mammalian target of rapamycin; IGF-1: insulin/insulin growth factor 1; DR: dietary restriction; ROS: reactive oxygen species; AMPK: AMP-activated protein kinase; HSCs: hematopoietic stem cells; NLRP3: nucleotide-binding domain, leucine rich family (NLR), pyrin containing 3; IL-1β: interleukin-1β; TNF: tumor necrosis factor.