hindlimb suspension


Summary: Technique for limiting use, activity, or movement by immobilizing or restraining animal by suspending from hindlimbs or tails. This immobilization is used to simulate some effects of reduced gravity and study weightlessness physiology.

Top Publications

  1. Ferreira R, Vitorino R, Neuparth M, Appell H, Duarte J, Amado F. Proteolysis activation and proteome alterations in murine skeletal muscle submitted to 1 week of hindlimb suspension. Eur J Appl Physiol. 2009;107:553-63 pubmed publisher
    ..different proteolytic systems and muscle proteome changes during experimental disuse atrophy (up to 1 week hindlimb suspension, HS) in murine gastrocnemius muscle...
  2. Cui Y, Zhang S, Zhang Q, Fan R, Li J, Guo H, et al. Modulation of intracellular calcium transient in response to beta-adrenoceptor stimulation in the hearts of 4-wk-old rats during simulated weightlessness. J Appl Physiol (1985). 2010;108:838-44 pubmed publisher
  3. Kwon R, Meays D, Tang W, Frangos J. Microfluidic enhancement of intramedullary pressure increases interstitial fluid flow and inhibits bone loss in hindlimb suspended mice. J Bone Miner Res. 2010;25:1798-807 pubmed publisher
  4. Labeit S, Kohl C, Witt C, Labeit D, Jung J, Granzier H. Modulation of muscle atrophy, fatigue and MLC phosphorylation by MuRF1 as indicated by hindlimb suspension studies on MuRF1-KO mice. J Biomed Biotechnol. 2010;2010:693741 pubmed publisher
    ..Here we studied MuRF1's role in muscle atrophy during muscle unloading induced by hindlimb suspension. Consistent with previous studies, we found that MuRF1 inactivation leads to an attenuated muscle atrophy ..
  5. Ogneva I. Transversal stiffness of fibers and desmin content in leg muscles of rats under gravitational unloading of various durations. J Appl Physiol (1985). 2010;109:1702-9 pubmed publisher
    ..The change of sarcolemma stiffness in activated fibers, which is due probably to the transfer of tension from the contractile apparatus, correlates with the dynamics of changes in the content of desmin...
  6. Hanson A, Harrison B, Young M, Stodieck L, Ferguson V. Longitudinal characterization of functional, morphologic, and biochemical adaptations in mouse skeletal muscle with hindlimb suspension. Muscle Nerve. 2013;48:393-402 pubmed publisher
    ..Muscle function and physiology were characterized at 0, 1, 3, 7, and 14 days of hindlimb suspension (HS). Reductions in muscle mass were maximal by Day 14 of HS...
  7. Zhang B, Yeung S, Liu Y, Wang H, Wan Y, Ling S, et al. The effects of low frequency electrical stimulation on satellite cell activity in rat skeletal muscle during hindlimb suspension. BMC Cell Biol. 2010;11:87 pubmed publisher
    ..It has been shown that chronic hindlimb unloading downregulates the satellite cell activity. This study investigated the role of low-frequency electrical stimulation on satellite cell activity during a 28 d hindlimb suspension in rats.
  8. Murphy K, Cobani V, Ryall J, Ibebunjo C, Lynch G. Acute antibody-directed myostatin inhibition attenuates disuse muscle atrophy and weakness in mice. J Appl Physiol (1985). 2011;110:1065-72 pubmed publisher
    ..These findings highlight the therapeutic potential of antibody-directed myostatin inhibition for disuse atrophy especially within the first 2 wk of disuse. ..
  9. Pellegrino M, Desaphy J, Brocca L, Pierno S, Camerino D, Bottinelli R. Redox homeostasis, oxidative stress and disuse muscle atrophy. J Physiol. 2011;589:2147-60 pubmed publisher
    ..A precise approach to determine the levels of ROS in living cells in various conditions appears to be of paramount importance to define and support such hypotheses. ..

More Information


  1. Washington T, White J, Davis J, Wilson L, Lowe L, Sato S, et al. Skeletal muscle mass recovery from atrophy in IL-6 knockout mice. Acta Physiol (Oxf). 2011;202:657-69 pubmed publisher
    ..was to determine the effect of IL-6 loss on mouse gastrocnemius (GAS) muscle mass during recovery from hindlimb suspension (HS)-induced atrophy...
  2. Xu J, Hwang J, Lees H, Wohlgemuth S, Knutson M, Judge A, et al. Long-term perturbation of muscle iron homeostasis following hindlimb suspension in old rats is associated with high levels of oxidative stress and impaired recovery from atrophy. Exp Gerontol. 2012;47:100-8 pubmed publisher
    ..study, we investigated the effects of 7 and 14 days of re-loading following 14-day muscle unweighting (hindlimb suspension, HS) on iron transport, non-heme iron levels and oxidative damage in the gastrocnemius muscle of young (6 ..
  3. Brocca L, Pellegrino M, Desaphy J, Pierno S, Camerino D, Bottinelli R. Is oxidative stress a cause or consequence of disuse muscle atrophy in mice? A proteomic approach in hindlimb-unloaded mice. Exp Physiol. 2010;95:331-50 pubmed publisher
    ..Trolox administration did not prevent metabolic adaptations in either Sol or Gas. The present findings suggest that oxidative stress is not a major determinant of muscle atrophy in HU mice...
  4. Desaphy J, Pierno S, Liantonio A, Giannuzzi V, Digennaro C, Dinardo M, et al. Antioxidant treatment of hindlimb-unloaded mouse counteracts fiber type transition but not atrophy of disused muscles. Pharmacol Res. 2010;61:553-63 pubmed publisher
    ..Trolox treatment had no effect on control mice. These results suggest possible benefits of antioxidants in protecting muscle against disuse...
  5. Vollenweider I, Smith K, Keist R, Rudolph U. Antidepressant-like properties of ?2-containing GABA(A) receptors. Behav Brain Res. 2011;217:77-80 pubmed publisher
    ..2-containing GABA(A) receptors may therefore represent a novel target for the development of more effective antidepressants. ..
  6. Roudier E, Gineste C, Wazna A, Dehghan K, Desplanches D, Birot O. Angio-adaptation in unloaded skeletal muscle: new insights into an early and muscle type-specific dynamic process. J Physiol. 2010;588:4579-91 pubmed publisher
  7. Magne H, Savary Auzeloux I, Migne C, Peyron M, Combaret L, Remond D, et al. Contrarily to whey and high protein diets, dietary free leucine supplementation cannot reverse the lack of recovery of muscle mass after prolonged immobilization during ageing. J Physiol. 2012;590:2035-49 pubmed publisher
    ..Thus, when supplemented with leucine-rich proteins (i.e. whey) and high protein diets, animals partially recovered the muscle mass loss...
  8. Kazi A, Hong Brown L, Lang S, Lang C. Deptor knockdown enhances mTOR Activity and protein synthesis in myocytes and ameliorates disuse muscle atrophy. Mol Med. 2011;17:925-36 pubmed publisher
    ..Thus, our data support the hypothesis that Deptor is an important regulator of protein metabolism in myocytes and demonstrate that decreasing Deptor expression in vivo is sufficient to ameliorate muscle atrophy. ..
  9. Jackson J, Ryan M, Hao Y, Alway S. Mediation of endogenous antioxidant enzymes and apoptotic signaling by resveratrol following muscle disuse in the gastrocnemius muscles of young and old rats. Am J Physiol Regul Integr Comp Physiol. 2010;299:R1572-81 pubmed publisher
    b>Hindlimb suspension (HLS) elicits muscle atrophy, oxidative stress, and apoptosis in skeletal muscle...
  10. Baptista I, Leal M, Artioli G, Aoki M, Fiamoncini J, Turri A, et al. Leucine attenuates skeletal muscle wasting via inhibition of ubiquitin ligases. Muscle Nerve. 2010;41:800-8 pubmed publisher
    ..It is notable that leucine supplementation does not restore decreased protein synthesis driven by immobilization. ..
  11. Zhou Y, Ni H, Li M, Sanzari J, Diffenderfer E, Lin L, et al. Effect of solar particle event radiation and hindlimb suspension on gastrointestinal tract bacterial translocation and immune activation. PLoS ONE. 2012;7:e44329 pubmed publisher
    ..Using models of reduced gravity and SPE radiation, we identify that either 2 Gy of radiation or hindlimb suspension alone leads to activation of the innate immune system and the two together are synergistic...
  12. Miller B, Schultz L, Long B, Pletcher M. Quantitative trait locus analysis identifies Gabra3 as a regulator of behavioral despair in mice. Mamm Genome. 2010;21:247-57 pubmed publisher
    ..This work suggests that GABRA3 regulates a behavioral endophenotype of depression and establishes this gene as a viable new target for the study and treatment of human depression. ..
  13. Ju Y, Sone T, Ohnaru K, Choi H, Fukunaga M. Differential effects of jump versus running exercise on trabecular architecture during remobilization after suspension-induced osteopenia in growing rats. J Appl Physiol (1985). 2012;112:766-72 pubmed publisher
  14. Magne H, Savary Auzeloux I, Vazeille E, Claustre A, Attaix D, Anne L, et al. Lack of muscle recovery after immobilization in old rats does not result from a defect in normalization of the ubiquitin-proteasome and the caspase-dependent apoptotic pathways. J Physiol. 2011;589:511-24 pubmed publisher
    ..These observations lead us to hypothesize that muscle protein synthesis activation after immobilization was altered during ageing...
  15. Hao Y, Jackson J, Wang Y, EDENS N, Pereira S, Alway S. ?-Hydroxy-?-methylbutyrate reduces myonuclear apoptosis during recovery from hind limb suspension-induced muscle fiber atrophy in aged rats. Am J Physiol Regul Integr Comp Physiol. 2011;301:R701-15 pubmed publisher
    ..The animals received either 14 days of hindlimb suspension (HS, n = 8/diet group) or 14 days of unloading followed by 14 days of reloading (R; n = 8/diet group)...
  16. Fujita N, Murakami S, Arakawa T, Miki A, Fujino H. The combined effect of electrical stimulation and resistance isometric contraction on muscle atrophy in rat tibialis anterior muscle. Bosn J Basic Med Sci. 2011;11:74-9 pubmed
    ..These results indicated that although electrical stimulation is effective to prevent muscle atrophy, the combination of electrical stimulation and isometric contraction have further effect...
  17. Imai S, Mamiya T, Tsukada A, Sakai Y, Mouri A, Nabeshima T, et al. Ubiquitin-specific peptidase 46 (Usp46) regulates mouse immobile behavior in the tail suspension test through the GABAergic system. PLoS ONE. 2012;7:e39084 pubmed publisher
    ..These results indicate that the 3-bp deleted Usp46 mutation causes a loss-of-function phenotype, and that the GABA(A) receptor might participate in the regulation of TST immobility time...
  18. Maki T, Yamamoto D, Nakanishi S, Iida K, Iguchi G, Takahashi Y, et al. Branched-chain amino acids reduce hindlimb suspension-induced muscle atrophy and protein levels of atrogin-1 and MuRF1 in rats. Nutr Res. 2012;32:676-83 pubmed publisher
    ..To test this hypothesis, we selected hindlimb suspension (HS)-induced muscle atrophy as a model of disuse muscle atrophy because it is an established model to ..
  19. Bajotto G, Sato Y, Kitaura Y, Shimomura Y. Effect of branched-chain amino acid supplementation during unloading on regulatory components of protein synthesis in atrophied soleus muscles. Eur J Appl Physiol. 2011;111:1815-28 pubmed publisher
    ..Short-term (6 days) hindlimb suspension of rats resulted in significant losses of myofibrillar proteins, total RNA, and rRNAs and pronounced ..
  20. Wagatsuma A. Effect of hindlimb unweighting on expression of hypoxia-inducible factor-1alpha vascular endothelial growth factor, angiopoietin, and their receptors in mouse skeletal muscle. Physiol Res. 2008;57:613-20 pubmed
    ..These findings suggest that alterations in expression of VEGF, angiopoietins, and their receptors may be associated with capillary regression after HU. ..
  21. Shimano M, Volpon J. Biomechanics and structural adaptations of the rat femur after hindlimb suspension and treadmill running. Braz J Med Biol Res. 2009;42:330-8 pubmed
    ..The bone disuse atrophy secondary to hypoactivity in rats can be reversed by an early regime of exercising, which is more advantageous than ordinary cage activities alone. ..
  22. Fuse A, Sato T. Effect of microgravity changes on virus infection in mice. J Gravit Physiol. 2004;11:P65-6 pubmed
    ..Responsibility of the immune system dependent on cytokines, including IFN, for down regulation of the resistance is also suggested. Tail-suspended mice were also less resistant to virus infection. ..
  23. Juszczak G, Sliwa A, Wolak P, Tymosiak Zielinska A, Lisowski P, Swiergiel A. The usage of video analysis system for detection of immobility in the tail suspension test in mice. Pharmacol Biochem Behav. 2006;85:332-8 pubmed
    ..The results obtained using the video analysis system were similar to the scores yielded by a human rater and the strain gauge device. ..
  24. Canu M, Stevens L, Falempin M. Effect of hindlimb suspension on activation and MHC content of triceps brachii and on the representation of forepaw on the sensorimotor cortex. Exp Neurol. 2007;203:521-30 pubmed
    ..Moreover, the new tonic pattern resulting from the long contact of the paw with the floor may contribute to the adaptation of the central control of motoneuronal activity. ..
  25. Guillot C, Steinberg J, Delliaux S, Kipson N, Jammes Y, Badier M. Physiological, histological and biochemical properties of rat skeletal muscles in response to hindlimb suspension. J Electromyogr Kinesiol. 2008;18:276-83 pubmed
    ..In control rats and after a 3-week period of hindlimb suspension (HS), the slow-oxidative (Soleus, SOL) and fast-glycolytic skeletal muscles (Extensor digitorum longus, EDL)..
  26. O Leary O, Bechtholt A, Crowley J, Hill T, Page M, Lucki I. Depletion of serotonin and catecholamines block the acute behavioral response to different classes of antidepressant drugs in the mouse tail suspension test. Psychopharmacology (Berl). 2007;192:357-71 pubmed
    ..In contrast, disruption of the behavioral effects of NRI and SSRI antidepressants required disruption of both catecholamine synthesis and vesicular storage and release mechanisms. ..
  27. Enns D, Raastad T, Ugelstad I, Belcastro A. Calpain/calpastatin activities and substrate depletion patterns during hindlimb unweighting and reweighting in skeletal muscle. Eur J Appl Physiol. 2007;100:445-55 pubmed
    ..83, P < 0.001). The results suggest that calpain activation is an early event during unloading in skeletal muscle, and that the majority of the increase in calpain activity can be attributed to the micro-isoform. ..
  28. Yasuhara T, Hara K, Maki M, Matsukawa N, Fujino H, Date I, et al. Lack of exercise, via hindlimb suspension, impedes endogenous neurogenesis. Neuroscience. 2007;149:182-91 pubmed
    ..Here, we explored the effects of lack of exercise on neurogenesis in rats by employing a routine hindlimb suspension (HS) model over a 2-week period, which consists of elevating their tails, thereby raising their hindlimbs ..
  29. Solich J, Pałach P, Budziszewska B, Dziedzicka Wasylewska M. Effect of two behavioral tests on corticosterone level in plasma of mice lacking the noradrenaline transporter. Pharmacol Rep. 2008;60:1008-13 pubmed
    ..The lack of effect of tianeptine in control animals (NET(+/+)) subjected to TST is also reflected in unchanged levels of plasma corticosterone. ..
  30. Ishihara A, Fujino H, Nagatomo F, Takeda I, Ohira Y. Gene expression levels of heat shock proteins in the soleus and plantaris muscles of rats after hindlimb suspension or spaceflight. J Physiol Sci. 2008;58:413-7 pubmed publisher
    ..proteins (HSPs) in the slow-twitch soleus and fast-twitch plantaris muscles of rats were determined after hindlimb suspension or spaceflight. Male rats were hindlimb-suspended for 14 d or exposed to microgravity for 9 d...
  31. Andreasen J, Redrobe J. Antidepressant-like effects of nicotine and mecamylamine in the mouse forced swim and tail suspension tests: role of strain, test and sex. Behav Pharmacol. 2009;20:286-95 pubmed publisher
    ..Nicotine was devoid of effects in the mTST, except in female C57BL/6J mice, where it increased immobility. We hypothesize that nicotine and mecamylamine produce antidepressant-like effects through partially different mechanisms. ..
  32. Takeda I, Fujino H, Murakami S, Kondo H, Nagatomo F, Ishihara A. Thermal preconditioning prevents fiber type transformation of the unloading induced-atrophied muscle in rats. J Muscle Res Cell Motil. 2009;30:145-52 pubmed publisher
    ..Therefore, thermal preconditioning provides a new approach to prevent disuse-induced fiber type transformation of skeletal muscle. ..
  33. Shenkman B, Litvinova K, Nemirovskaya T, Podlubnaya Z, Vikhlyantsev I, Kozlovskaya I. Afferent and peripheral control of muscle fiber properties during gravitational unloading. J Gravit Physiol. 2004;11:P111-4 pubmed
    ..Thus it is concluded that resting Ca2+ accumulation in the unloaded fibers may be among the mechanisms involved in the changes of fiber properties during unloading. ..
  34. De Doncker L, Kasri M, Picquet F, Falempin M. Physiologically adaptive changes of the L5 afferent neurogram and of the rat soleus EMG activity during 14 days of hindlimb unloading and recovery. J Exp Biol. 2005;208:4585-92 pubmed
    ..To conclude, our study directly demonstrates that the HU conditions cannot be considered as a functional deafferentation, as suggested in the literature, but only as a reduction of afferent information at the beginning of the HU period. ..
  35. Stevens H, Meays D, Frangos J. Pressure gradients and transport in the murine femur upon hindlimb suspension. Bone. 2006;39:565-72 pubmed
    ..transport of oxygen was assessed by the levels of hypoxic osteocytes in mouse femur after disuse by hindlimb suspension and with or without femoral vein ligation...
  36. Caron A, Drouin G, Desrosiers J, Trensz F, Grenier G. A novel hindlimb immobilization procedure for studying skeletal muscle atrophy and recovery in mouse. J Appl Physiol (1985). 2009;106:2049-59 pubmed publisher
    ..This model offers unexpected new insights into the molecular events involved in immobilization atrophy. ..
  37. Arbogast S, Smith J, Matuszczak Y, Hardin B, Moylan J, Smith J, et al. Bowman-Birk inhibitor concentrate prevents atrophy, weakness, and oxidative stress in soleus muscle of hindlimb-unloaded mice. J Appl Physiol (1985). 2007;102:956-64 pubmed
    ..We conclude that dietary supplementation with BBIC protects skeletal muscle during prolonged unloading, promoting redox homeostasis in muscle fibers and blunting atrophy-induced weakness. ..
  38. Bloomfield S. Does altered blood flow to bone in microgravity impact on mechanotransduction?. J Musculoskelet Neuronal Interact. 2006;6:324-6 pubmed
  39. Ono N, Nakashima K, Schipani E, Hayata T, Ezura Y, Soma K, et al. Constitutively active parathyroid hormone receptor signaling in cells in osteoblastic lineage suppresses mechanical unloading-induced bone resorption. J Biol Chem. 2007;282:25509-16 pubmed
    ..These results indicated that constitutive activation of PTH/PTHrP receptor signaling in osteoblastic cells suppresses unloading-induced bone loss specifically through the regulation of osteoclastic activity. ..
  40. Wang K, Shi Y, Denhardt D. Osteopontin regulates hindlimb-unloading-induced lymphoid organ atrophy and weight loss by modulating corticosteroid production. Proc Natl Acad Sci U S A. 2007;104:14777-82 pubmed
    ..These results reveal that OPN is required for enhanced corticosterone production, immune organ atrophy, and weight loss in mice subjected to HU. ..
  41. Cornachione A, Cação Benedini L, Shimano M, Volpon J, Martinez E, Mattiello Sverzut A. Morphological comparison of different protocols of skeletal muscle remobilization in rats after hindlimb suspension. Scand J Med Sci Sports. 2008;18:453-61 pubmed
    ..of different remobilization protocols in different skeletal muscles considering the changes induced by hindlimb suspension of the tail...
  42. Litvinova K, Tarakin P, Fokina N, Istomina V, Larina I, Shenkman B. [Reloading of rat soleus after hindlimb unloading and serum insulin-like growth factor 1]. Ross Fiziol Zh Im I M Sechenova. 2007;93:1143-55 pubmed
    The aim of this study was to elucidate the effects of 14- day hindlimb suspension (HS) and subsqquent reloading (3 or 7 days) on the m. soleus mass, muscle fiber cross-sectional area (CSA), soleus fiber properties and serum IGF-1 in rats...
  43. Eash J, Olsen A, Breur G, Gerrard D, Hannon K. FGFR1 inhibits skeletal muscle atrophy associated with hindlimb suspension. BMC Musculoskelet Disord. 2007;8:32 pubmed
    ..the effects of ectopic expression of FGFR1 during disuse-mediated skeletal muscle atrophy, utilizing hindlimb suspension and DNA electroporation in mice...
  44. Boonyarom O, Kozuka N, Matsuyama K, Murakami S. Effect of electrical stimulation to prevent muscle atrophy on morphologic and histologic properties of hindlimb suspended rat hindlimb muscles. Am J Phys Med Rehabil. 2009;88:719-26 pubmed publisher
  45. Lad H, Liu L, Paya Cano J, Fernandes C, Schalkwyk L. Quantitative traits for the tail suspension test: automation, optimization, and BXD RI mapping. Mamm Genome. 2007;18:482-91 pubmed
    ..A second trial of the test has greater duration of immobility and a completely different genetic profile. Frequency of mobility is also an independent phenotype, with a distal chromosome 1 locus. ..
  46. Liu X, Stancliffe D, Lee S, Mathur S, Gershenfeld H. Genetic dissection of the tail suspension test: a mouse model of stress vulnerability and antidepressant response. Biol Psychiatry. 2007;62:81-91 pubmed
    ..These QTL provide potential regions of interest for human genetic studies in stress-diathesis models of psychiatric illness and antidepressant responsiveness. ..
  47. Pierno S, Desaphy J, Liantonio A, De Luca A, Zarrilli A, Mastrofrancesco L, et al. Disuse of rat muscle in vivo reduces protein kinase C activity controlling the sarcolemma chloride conductance. J Physiol. 2007;584:983-95 pubmed
    ..In conclusion, Sol muscle disuse is characterized by a rapid reduction of PKC activity, which reduces muscle excitability and is likely to contribute to disuse-induced muscle impairment. ..
  48. Mineur Y, Belzung C, Crusio W. Effects of unpredictable chronic mild stress on anxiety and depression-like behavior in mice. Behav Brain Res. 2006;175:43-50 pubmed
    ..The goals of these experiments are to obtain a clearer behavioral profile of genetically/phenotypically distant mouse strains after UCMS treatment and to evaluate the limitations and strengths of the UCMS model in mice. ..
  49. Crowley J, Brodkin E, Blendy J, Berrettini W, Lucki I. Pharmacogenomic evaluation of the antidepressant citalopram in the mouse tail suspension test. Neuropsychopharmacology. 2006;31:2433-42 pubmed
    ..The present quantitative trait study suggests possible candidate genes for human pharmacogenetic studies of therapeutic responses to SSRIs such as citalopram. ..
  50. Bondesen B, Mills S, Pavlath G. The COX-2 pathway regulates growth of atrophied muscle via multiple mechanisms. Am J Physiol Cell Physiol. 2006;290:C1651-9 pubmed
    ..Muscle atrophy was induced by hindlimb suspension (HS) for 2 wk, followed by a reloading period, during which mice were treated with either the COX-2-..
  51. Bigbee A, Grindeland R, Roy R, Zhong H, Gosselink K, Arnaud S, et al. Basal and evoked levels of bioassayable growth hormone are altered by hindlimb unloading. J Appl Physiol (1985). 2006;100:1037-42 pubmed
    ..Thus BGH may play a role in muscle, bone, and metabolic adaptations that occur in response to chronically unloaded states. ..
  52. Haddad F, Adams G, Bodell P, Baldwin K. Isometric resistance exercise fails to counteract skeletal muscle atrophy processes during the initial stages of unloading. J Appl Physiol (1985). 2006;100:433-41 pubmed
  53. Vazeille E, Codran A, Claustre A, Averous J, Listrat A, Bechet D, et al. The ubiquitin-proteasome and the mitochondria-associated apoptotic pathways are sequentially downregulated during recovery after immobilization-induced muscle atrophy. Am J Physiol Endocrinol Metab. 2008;295:E1181-90 pubmed publisher
  54. Oishi Y, Ogata T, Yamamoto K, Terada M, Ohira T, Ohira Y, et al. Cellular adaptations in soleus muscle during recovery after hindlimb unloading. Acta Physiol (Oxf). 2008;192:381-95 pubmed
    ..Furthermore, it appears that CaN is related to fibre size and phenotype adaptations, but not to apoptotic responses. ..