Table 3.

Examples of Myokines Released During Exercise with a Potential Anti-Aging Effect

Name of molecule	Main tissue(s) of origin	Main type of exercise inducing its release/secretion	Main target tissue(s)	Main biological effect(s) associated with exercise-induced release/secretion	Main aging hallmark targeted	Potential future anti-aging application	Illustrative references
Brain-derived neurotrophic factor (BDNF)	Central nervous system Vascular endothelial cells, platelets, lymphocytes, eosinophils, monocytes, pituitary gland, working skeletal muscle	Moderate-intense “aerobic” exercise (e.g., brisk walking)	Brain Motor neurons	↑ Neuroplasticity ↑ Motor unit regeneration	Cellular senescence in the brain	Protection against neurodegeneration (including possibly dementia)	167–169
Interleukin-4 (IL-4) and IL-13	Lymphocytes, mast cells and neutrophils Various origins (brain, cancer cells, liver, fibroblasts, and muscle cells) Working muscles	Resistance exercise (e.g., weightlifting)	Skeletal muscle	↑ Muscle growth	Loss of muscle proteostasis	Aging muscle atrophy/sarcopenia	387–389
IL-6 (also termed interferon, beta 2)	Working muscles Immune cells Adipocytes	Intense ‘aerobic’ exercise (e.g., brisk/very brisk walking)	Skeletal muscle Adipose tissue Pituitary gland-liver Immune cells	↑ Muscle lipolysis ↑ Muscle growth ↑ Adipocyte lipolysis ↑ Liver-glucose release to blood ↓Inflammation ↑Immunomodulation	Altered inter-cellular communication (‘inflammaging’)	Age-related cardio-metabolic diseases	129, 390–393
IL-15	Working muscles Various origins (lymphoid tissues, kidney, brain, cardiac muscle, lung, pancreas, testis, liver, placenta, epithelial cells, and activated macrophages, and maybe adipocytes)	Mainly resistance exercise	Skeletal muscle Adipose tissue	Promotes muscle anabolism/inhibits catabolism Anti-obesogenic (↓mainly visceral fat) effect Insulin-sensitizing effect	Loss of muscle proteostasis	Aging muscle wasting/sarcopenia	394–397
Leukemia inhibitory factor (LIF)	Working muscles Central nervous system	Mainly resistance exercise	Skeletal muscle	Mainly local (autocrine/paracrine effect): ↑ Muscle growth (satellite cell proliferation) ↑ Muscle regeneration	Loss of muscle proteostasis	Aging muscle wasting/sarcopenia	398–401
Myostatin (also termed, growth differentiation factor 8 [GDF8])	Skeletal muscle	Both “aerobic” and resistance exercise	Skeletal muscle Adipose tissue	Main effects associated to myostatin inhibition which can be partly achieved by exercise are: ↑Muscle growth ↓Adiposity ↑Insulin sensitivity	Attenuation of disease/age muscle wasting Obesity/diabetes prevention	Use of exercise as a coadjuvant of myostatin-inhibition therapies for muscle wasting	402–406
Visfatin (also known as (nicotinamide phosphoribosyltransferase [NAMPT] or pre-B cell enhancing factor [PBEF])	Ubiquitous expression in human tissues, including adipose and skeletal muscle tissue (i.e., it is both an adypokine and a myokine), liver, bone marrow, lymphocytes, β-cells and human islets, heart	“Aerobic” exercise	Skeletal muscle and adipose tissue	AMPK activation→↑ sirtuin1 (SIRT1)→peroxisome proliferator-activated receptor γ co-activator α (PGC-1α) It provides NAD+	Mitochondrial dysfunction	Exercise as a major component of anti-aging medicine	407–410

The information provided in the table is based (and adapted from) a previous review paper by the authors.¹¹¹

AMPK AMP-activated protein kinase; NAD⁺, oxidized nicotinamide adenine dinucleotide.