Table 2.

Summary of main inflammatory and myeloid cell alterations in age-related diseases

Age-related disease	Inflammatory and myeloid cell alterations			References
CVDs Atherosclerosis	DAMPs (e.g., HMGB1, HSP60) and PAMPs (e.g., C. pneumoniae) early activate PRR- and scavenger receptor-expressing immune cells (i.e., macrophages, neutrophils)			[117]
	CRP, IL-1β, IL-6, and TNFα levels positively correlate with myocardial infarction and stroke			[118]
	LDL particles:	• Trigger monocyte recruitment into atheroma, macrophage differentiation and activation		[114, 119]
		• Generate foam cells with increased TLRs/NLRP3 inflammasome activation followed by massive release of pro-inflammatory cytokines (e.g., IL-1β, IL-18)
	TNFα, IL-6, and IL-1β released by cardiomyocytes correlate with increased risk for CVDs, progression of myocardial dysfunctions and with short-term survival			[34, 110, 111, 118]
Obesity	Adipose tissue releases high levels of inflammatory cytokines (i.e., IL-6, IL-1β, TNFα, CCL2) and hormones (i.e., leptin), inducing the recruitment of immune cells (macrophage, T cell)			[34, 129]
	TNFα and IL-6 promotes, whereas IL-10 prevents, obesity-associated insulin resistance			[130]
	Adipose tissue neutrophils (ATN) and macrophages (ATM) highly infiltrate fat depots, perpetuating tissue inflammation and cytokine release			[34, 133]
Diabetes	Insulin resistance/hyperglycemia are associated with increased TNFα, IL-6, and CRP levels, correlating with high oxidative stress			[138, 139]
	Reduced phagocytic capacity, TLR responsiveness, and increased apoptosis of monocytes and neutrophils			[140, 141]
Neurodegenerative disorders	Triggering events (e.g., infection, trauma) induce the Aβ production by CNS cells and activate resident immune cell (i.e., microglia) via TLRs, and thus recruiting peripheral immune cells			[111]
	Senescent microglia:	• Higher proliferative rate with subsequent shortening of telomeres and cytokines release		[150]
		• Reduced phagocytic capacity of Aβ fibrils		[151–153]
		• Accumulation of damaged mitochondrial DNA inducing ROS overproduction and TLRs overexpression		[151–153]
		• Promoted by accumulation of misfolded protein and by chronic exposure to TGFβ		[153, 154]
	Aβ plaques recruit peripheral mono/macrophages with increased expression of CD14 and TLRs, and MHC-II-antigen presentation, as well as increased M1 macrophage polarization			[151, 155, 156]
Sarcopenia	Old subjects with sepsis-induced inflammation experience muscle loss and changes in muscle cell functionality			[162]
	Obesity- and T2DM-associated inflammatory alterations co-occur with sarcopenia in old subjects			[109, 164]
	Inflammaging impairs insulin sensitivity, hormonal production and vascular functionality, contributing to the reduction of muscular strength and alterations of energy metabolism			[165]
	IL-6, TNFα, CRP:		• Promote muscle adiposity and reduce IGF-1-dependent protein synthesis homeostasis in myocytes	[165]
			• Correlate with poor overall physical performance and reduced lean mass and muscle strength	[167]
			• Reduce mitochondrial oxidative capacity and increase NF-κB activation	[167]

DAMP damage-associated molecular pattern, HMGB1 high-mobility group box 1, HSP60 heat shock protein 60, PAMP pathogen-associated molecular pattern, PRR pattern recognition receptor, CRP C reactive protein, IL interleukin, TNF tumor necrosis factor, TLR Toll-like receptor, NLRP3 NLR family pyrin domain containing 3, CVD cardiovascular disease, CCL2 C–C motif chemokine ligand 2, Aβ amyloid beta, CNS central nervous system, ROS reactive oxygen species, TGF transforming growth factor, MHC major histocompatibility complex, T2DM type-2 diabetes mellitus, IGF-1 insulin-like growth factor 1, NF–κB nuclear factor kappa-light-chain-enhancer of activated B cells