Tchkonia, T., Zhu, Y., van Deursen, J., Campisi, J. & Kirkland, J.L. Cellular senescence and the senescent secretory phenotype: therapeutic opportunities. J. Clin. Invest. 123, 966–972 (2013).
Baker, D.J. et al. Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders. Nature 479, 232–236 (2011).
Xu, M. et al. Targeting senescent cells enhances adipogenesis and metabolic function in old age. eLife 4, e12997 (2015).
Roos, C.M. et al. Chronic senolytic treatment alleviates established vasomotor dysfunction in aged or atherosclerotic mice. Aging Cell 15, 973–977 (2016).
Zhu, Y. et al. The Achilles' heel of senescent cells: from transcriptome to senolytic drugs. Aging Cell 14, 644–658 (2015).
Kirkland, J.L. & Tchkonia, T. Clinical strategies and animal models for developing senolytic agents. Exp. Gerontol. 68, 19–25 (2015).
Xu, M. et al. JAK inhibition alleviates the cellular senescence-associated secretory phenotype and frailty in old age. Proc. Natl. Acad. Sci. USA 112, E6301–E6310 (2015).
LeBrasseur, N.K., Tchkonia, T. & Kirkland, J.L. Cellular senescence and the biology of aging, disease, and frailty. Nestle Nutr. Inst. Workshop Ser. 83, 11–18 (2015).
Swanson, E.C., Manning, B., Zhang, H. & Lawrence, J.B. Higher-order unfolding of satellite heterochromatin is a consistent and early event in cell senescence. J. Cell Biol. 203, 929–942 (2013).
Zhu, Y., Armstrong, J.L., Tchkonia, T. & Kirkland, J.L. Cellular senescence and the senescent secretory phenotype in age-related chronic diseases. Curr. Opin. Clin. Nutr. Metab. Care 17, 324–328 (2014).
Campisi, J. & d'Adda di Fagagna, F. Cellular senescence: when bad things happen to good cells. Nat. Rev. Mol. Cell Biol. 8, 729–740 (2007).
Campisi, J. Senescent cells, tumor suppression, and organismal aging: good citizens, bad neighbors. Cell 120, 513–522 (2005).
Jurk, D. et al. Postmitotic neurons develop a p21-dependent senescence-like phenotype driven by a DNA damage response. Aging Cell 11, 996–1004 (2012).
Jurk, D. et al. Chronic inflammation induces telomere dysfunction and accelerates ageing in mice. Nat. Commun. 5, 4172 (2014).
Minamino, T. et al. A crucial role for adipose tissue p53 in the regulation of insulin resistance. Nat. Med. 15, 1082–1087 (2009).
Farr, J.N. et al. Identification of senescent cells in the bone microenvironment. J. Bone Miner. Res. 31, 1920–1929 (2016).
Wang, E. Senescent human fibroblasts resist programmed cell death, and failure to suppress bcl2 is involved. Cancer Res. 55, 2284–2292 (1995).
Nelson, G. et al. A senescent cell bystander effect: senescence-induced senescence. Aging Cell 11, 345–349 (2012).
Coppé, J.P., Desprez, P.Y., Krtolica, A. & Campisi, J. The senescence-associated secretory phenotype: the dark side of tumor suppression. Annu. Rev. Pathol. 5, 99–118 (2010).
Acosta, J.C. et al. A complex secretory program orchestrated by the inflammasome controls paracrine senescence. Nat. Cell Biol. 15, 978–990 (2013).
Herbig, U., Ferreira, M., Condel, L., Carey, D. & Sedivy, J.M. Cellular senescence in aging primates. Science 311, 1257 (2006).
Hamrick, M.W. et al. Age-related loss of muscle mass and bone strength in mice is associated with a decline in physical activity and serum leptin. Bone 39, 845–853 (2006).
Glatt, V., Canalis, E., Stadmeyer, L. & Bouxsein, M.L. Age-related changes in trabecular architecture differ in female and male C57BL/6J mice. J. Bone Miner. Res. 22, 1197–1207 (2007).
Silva, M.J., Brodt, M.D. & Uthgenannt, B.A. Morphological and mechanical properties of caudal vertebrae in the SAMP6 mouse model of senile osteoporosis. Bone 35, 425–431 (2004).
Oliver, W.C. & Pharr, G.M. An improved technique for determining hardness and elastic modulus using load and displacement sensing indentation experiments. J. Mater. Res. 7, 1564–1583 (1992).
McGee-Lawrence, M.E. et al. Histone deacetylase 3 is required for maintenance of bone mass during aging. Bone 52, 296–307 (2013).
Qing, H. et al. Demonstration of osteocytic perilacunar/canalicular remodeling in mice during lactation. J. Bone Miner. Res. 27, 1018–1029 (2012).
Yi, J.-S. et al. Low-dose dasatinib rescues cardiac function in Noonan syndrome. JCI Insight 1, e90220 (2016).
D'Andrea, G. Quercetin: A flavonol with multifaceted therapeutic applications? Fitoterapia 106, 256–271 (2015).
Arai, F. et al. Commitment and differentiation of osteoclast precursor cells by the sequential expression of c-Fms and receptor activator of nuclear factor kappaB (RANK) receptors. J. Exp. Med. 190, 1741–1754 (1999).
Bellido, T. et al. Regulation of interleukin-6, osteoclastogenesis, and bone mass by androgens. The role of the androgen receptor. J. Clin. Invest. 95, 2886–2895 (1995).
Bendre, M.S. et al. Interleukin-8 stimulation of osteoclastogenesis and bone resorption is a mechanism for the increased osteolysis of metastatic bone disease. Bone 33, 28–37 (2003).
Daci, E., Verstuyf, A., Moermans, K., Bouillon, R. & Carmeliet, G. Mice lacking the plasminogen activator inhibitor 1 are protected from trabecular bone loss induced by estrogen deficiency. J. Bone Miner. Res. 15, 1510–1516 (2000).
Khosla, S. Odanacatib: location and timing are everything. J. Bone Miner. Res. 27, 506–508 (2012).
Mullard, A. Merck & Co. drops osteoporosis drug odanacatib. Nat. Rev. Drug Discov. 15, 669 (2016).
Lyles, K.W. et al. Zoledronic acid and clinical fractures and mortality after hip fracture. N. Engl. J. Med. 357, 1799–1809 (2007).
Zhu, Y. et al. Identification of a novel senolytic agent, navitoclax, targeting the Bcl-2 family of anti-apoptotic factors. Aging Cell 15, 428–435 (2016).
Wright, N.C. et al. The recent prevalence of osteoporosis and low bone mass in the United States based on bone mineral density at the femoral neck or lumbar spine. J. Bone Miner. Res. 29, 2520–2526 (2014).
Burge, R. et al. Incidence and economic burden of osteoporosis-related fractures in the United States, 2005-2025. J. Bone Miner. Res. 22, 465–475 (2007).
Stern, A.R. et al. Isolation and culture of primary osteocytes from the long bones of skeletally mature and aged mice. Biotechniques 52, 361–373 (2012).
Lee, B.Y. et al. Senescence-associated beta-galactosidase is lysosomal beta-galactosidase. Aging Cell 5, 187–195 (2006).
Syed, F.A. et al. Skeletal effects of estrogen are mediated by opposing actions of classical and nonclassical estrogen receptor pathways. J. Bone Miner. Res. 20, 1992–2001 (2005).
Tchkonia, T. et al. Abundance of two human preadipocyte subtypes with distinct capacities for replication, adipogenesis, and apoptosis varies among fat depots. Am. J. Physiol. Endocrinol. Metab. 288, E267–E277 (2005).
Takeshita, S., Kaji, K. & Kudo, A. Identification and characterization of the new osteoclast progenitor with macrophage phenotypes being able to differentiate into mature osteoclasts. J. Bone Miner. Res. 15, 1477–1488 (2000).
Gingery, A., Bradley, E., Shaw, A. & Oursler, M.J. Phosphatidylinositol 3-kinase coordinately activates the MEK/ERK and AKT/NFkappaB pathways to maintain osteoclast survival. J. Cell. Biochem. 89, 165–179 (2003).