Current Trauma Reports

, Volume 3, Issue 1, pp 8–12 | Cite as

Changes in Organ Physiology in the Aging Adult

Geriatric Trauma (F Luchette, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Geriatric Trauma


Purpose of Review

Recent advances in geriatric medicine and the aging of organ physiology affect the available clinical understanding and treatments for geriatric trauma patients.

Recent Findings

The effects of aging on organ physiology are complex and interlinked. There are global cellular changes and molecular and cellular changes specific to individual organ systems that affect the host response to trauma in the elderly.


As a n improved understanding of the physiologic changes of aging at the organ level allows application to a variety of clinical scenarios; we have better understanding of the host response to trauma at an older age.


Geriatric trauma Organ physiology Aging adult 


By 2050, it is expected that there will be nearly 90 million adults over the age of 65 in the USA, representing more than one-fifth of the population [1]. As this group is living longer and healthier, trauma has emerged as an increasing cause of death and disability. While increases in mortality for injury have been observed as young as 50, recent data suggests that mortality as adjusted for injury severity scale (ISS) escalates sharply at the age of 70 [2]. Successful treatment of geriatric trauma patients requires complex decisions and should be based upon a firm understanding of the physiologic and cellular mechanisms that affect the aging process. While much research has been devoted to the aging process on a cellular level, it is now understood that the process is multifactorial and therefore the associated clinical considerations must be multifactorial as well [3].

The effects of aging are observed at both the cellular and tissue level, leading to changes in organ function. These alterations have traditionally been attributed to oxidative stress, shortening telomeres, or fatty replacement of tissue. Aging cells also demonstrate decreased proliferative potential secondary to defects in DNA mismatch repair [4••]. Telomere shortening manifests clinically as liver cirrhosis, pulmonary fibrosis, and increased risk of cancer; and has been implicated in cellular aging, although evidence continues to be debated [5]. Despite conflicting data, telomere shortening, along with genomic instability, is implicated by most as a sensitive marker of aging and senescence at the tissue level [6]. In a randomized controlled trial, danazol has been shown to increase telomere length; however, these preliminary data require more rigorous clinical study. While there are theoretical implications for the use of androgenic steroids to belay telomere associated aging, much more study is needed in this area to fully elucidate the risks and benefits of this therapy [7••].

It is understood that while the physiologic changes of aging occur in all, they can be accelerated in some due to individual lifestyle and experience factors, including early reproduction in females, substance use and abuse, disease and medication use, or stress [8]. From recent research, two theoretical frameworks have arisen. The first is the developmental model of early life stress, which suggests that stressors in early life lead to telomere erosion and increased oxidative stress. Childhood stress and trauma have been demonstrated to result in irrevocable epigenetic changes in cortisol receptors, for example. The second framework, built on the evolutionary theories of aging, suggests that reproductive effort is associated with the same processes of shortened telomeres and oxidative stress. These theories are merging into a two-hit hypothesis that would accelerate aging in individuals with early life stress and early reproduction.

Decreased proliferation of lymphocyte progenitor cells is observed with aging leading to an imbalance with megakaryocytes and erythrocyte progenitors, with downstream effects on all tissues [9•]. Transcription changes are also seen that cause immunosenescence and imbalances in the levels of coagulation factors, leading to a relatively hypercoagulable state and relatively lower ability of the stressed host to respond to trauma on a systemic level [10]. The manipulation of the process of gene expression in stem cells to change the hematopoietic balance is a subject of significant interest in potential therapies to decrease the effects of aging on the immune and hematopoietic system and the subsequent systemic effects of these systems [11].

The tissue and organ effects of aging may arise from the same cellular mechanisms, but they manifest in different ways in different tissue types. Furthermore, aging can create a cycle where organ dysfunction may both precipitate trauma and decrease functional recovery, leading to increased disability and worsening organ function. For example, senescence in the vestibular and musculoskeletal systems can lead to decreased balance and spatial awareness leading to falls. Decreased physiologic reserve and ability to recover from these fall injuries can lead to decreased healing capacity of bony tissue and ultimately more fall injuries. Specific examples of the effects of senescence in tissues of interest in trauma are discussed below.


The brain has long been known to experience age-related changes with cerebral atrophy manifesting as loss of volume of gray and white matter. Neurofibrillary tangles, amyloid deposits, and oxidative stress all contribute to neuronal loss. In addition, microvascular changes lead to tissue hypoxia and microscopic ischemic events. In fact, cerebrovascular microangiopathy and vascular dementia are secondary only to Alzheimer’s disease in causes of dementia [12].

In addition to anatomic changes, the importance of functional relationships and connectivity between areas of the brain changes in neuronal networks is increasingly recognized. For example, the hippocampus is functionally connected to the brain’s default mode network, allowing encoding and retrieval of memories. However, there is increased hippocampal connectivity seen in older adults, owed to decreased inhibition in the network [13]. Additionally, with the advent of advanced genetic sequencing and amplification techniques, a large body of research is devoted to genetic risk factors that impart increased risk of cognitive decline, such apolipoprotein E4 in Alzheimer’s disease or Hp1bp3 in hippocampal tissue [14, 15].

Much of the current clinical research focuses on ways to augment the changes seen in the brain through lifestyle modification. Diet and exercise increase cognitive reserve and promote retained brain function with aging [16•]. Of specific interest is the benefit of exercise on cerebrovascular health as a mechanism of increasing overall brain health [17]. Control of hypertension has been shown to reduce hemorrhagic strokes. Unfortunately, no study has definitively shown a benefit of this therapy in decreasing the incidence of vascular dementia [18] and trauma surgeons see and treat increasing numbers of geriatric patients whose rigid blood pressure control has precipitated a fall.

Additionally, there has been clear recognition that there are long-term consequences of repeated concussion and sports injuries. It is possible that more subtle and occult changes are not immediately manifested in chronic traumatic encephalopathy, but may play a role in age-related deterioration in brain function. The history of such events may be remote or even unknown and may represent clinically significant traumatic brain events over the lifetime [19].

An integral part of neurologic aging is changes within the vestibular system [20]. In the aging population, the incidence of benign positional vertigo peaks at the age of 60 [21]. The initial cause was thought to be free floating particles in the semicircular canals, as well as microfractures in the temporal bone that accumulate with age [22]. With improved microscopic techniques, however, it has been established that hair cells within the semicircular canals of the vestibular-cochlear complex decrease in a linear fashion from birth [23]. Using vestibular evoked myogenic potentials in conjunction with head thrust test have demonstrated that the vestibular complex does indeed show decline in function, as expected, from the previous structural studies [24]. However, this decline does not fully account for the overall decline in vestibular awareness in adults over the age of 70. This suggests a component of the oculomotor function as well as vestibular function, or perhaps central integration of peripheral data, as contributing factors to vertigo in aging adults [25]. With an estimated 10 to 20 billion dollars in annual cost of elderly fall-related injuries, and a 20 % mortality rate, the personal and monetary costs of falls are staggering. An evolving understanding of the effects of age on the vestibular system is important if we are to better understand and manage the clinical implications of balance disorders and falls.


Aging in the cardiovascular system has long been thought to be due to normal senescence, genetic risk factors, diabetes, hyperlipidemia, and modifiable risk factors such as smoking and diet. The increase in vascular stiffness that accompanies aging results in increased systolic blood pressure, widened pulse pressure, and increased pulse wave velocity typically seen in individuals over the age of 50. This change in vasculature, which manifests clinically as orthostatic hypotension, is an independent risk factor for future cardiovascular disease [26].

Recent research has focused on other factors than simply the stiffening of the peripheral arteries as a mechanism for decline in cardiac function with aging. Study of the complex relationship between the autonomic nervous system and the cardiovascular system suggests that decline in autonomic function is a risk factor for increased pulse wave pressure and therefore cardiovascular disease, independent of traditional cardiovascular risk factors such as BMI and heart rate [27]. Endothelial dysfunction as a cause of senescent aging in both normal adults and those at increased cardiovascular risk has also been implicated. Endothelial dysfunction is an independent risk factor for future microvascular events of any kind [28]. In addition, increased afterload caused by subendocardial dysfunction leads to a reduction in cardiac output [29•].

Clinical studies related to cardiovascular aging focus on mitigating known cardiovascular risk factors through the use of lifestyle modifications and longstanding therapies such as beta blockade. However, recent studies also demonstrate the benefit of assessing frailty rather than focusing particularly on assessing cardiovascular risk and health, which is neither age nor disease-specific [30]. There is little doubt that cardiac senescence increases the complexity and morbidity of trauma related to decreased cardiovascular reserve for a major, or even relatively modest, traumatic insult.


Musculoskeletal aging is widely variable between individuals [31], and the recent success by “older” athletes at the 2016 summer Olympic Games demonstrates that it is possible to maintain musculoskeletal fitness far longer than previously thought possible. Aging in the musculoskeletal system is measured by four interwoven factors: osteoporosis, osteoarthritis, sarcopenia, and frailty [32]. At the tissue level, muscular and skeletal aging are due to complex interactions of hormones, disuse, growth factors, nutrition, and genetics, but should be understood to be interrelated, rather than two separate body systems [33].

With aging, type 1 muscle fibers are replaced with slower type 2 fibers which results in less stimulation and encourages fat deposition and collagen formation, which ultimately results in muscle weakness [34]. Disuse atrophy has long been recognized clinically; however, the molecular features that drive proteolysis during disuse atrophy are complex. Animal models have suggested that initiation of these pathways includes free radical oxygen species which may be treated with antioxidant therapy [35, 36].

Studies on muscle atrophy and hypertrophy have also shed light on age-related changes. Myocytes are the largest cells in the body and are multinucleated and syncytial. Traditional models postulated that muscular hypertrophy was due to muscle stem, or satellite cells, fusing with myocytes to increase the number of myonuclei and proportionately increase in the amount of surrounding cytoplasm. During atrophy of these muscles, the myonuclei underwent apoptosis [37]. Newer imaging and staining technology, however, has demonstrated that the number of myonuclei remains constant during atrophy and that the surrounding cytoplasm simply regresses [38••]. This is thought to be the mechanism behind “muscle memory” but also has clinical implications in that exercise, specifically muscle training, earlier in life may decrease the degree of senescence of the muscular system [39].

The most severe muscle wasting observed following trauma and critical illness is critical illness myopathy and cachexia. In addition to myonuclei involvement in atrophy and hypertrophy, much study has been directed to the pathologies that govern systemic muscle wasting [40]. This is caused by numerous mechanisms including reduced nutrition, alterations in protein synthesis and degradation pathways, neuromuscular blockade, and an increase in insulin resistance [41]. Net protein accumulation is governed by the suppression of forkhead box protein and the ubiquitin-proteasome system, both of which cause protein degradation and are suppressed under normal circumstances [42, 43]. Activation of these cascades during critical illness myopathy leads to cachexia.

Sarcopenia is a syndrome characterized by progressive and generalized loss of skeletal muscle mass and strength with a risk of adverse outcomes such as physical disability, poor quality of life, and death [44•]. Clinically, sarcopenia is a risk factor for any major surgical procedure, including trauma [45]. In the normal aging adult, sarcopenia is likely the most observed finding and yet the least well understood. Little study exists into the molecular pathways causing sarcopenia, but the histologic changes, particularly in the mitochondria, are suggestive of denervation atrophy [46] in combination with the loss of influence of testosterone and growth hormone in both sexes during senescence [47]. However, hormonal replacement therapy has not been shown effective. Myostatin is being studied as a potential therapeutic target. The myostatin-activin A pathway is activated in elderly adults, and blocking myostatin has been shown to increase muscle mass in sarcopenic mice [48]. Further study is needed to show if pharmacologic treatment directed at molecular pathways will be of benefit in humans.

Osteoporosis, defined as a loss of bone mineral density and subsequent bone fragility, and net loss of bone tissue, [49] disproportionately affects aging women secondary to the effects of declining estrogen on the bone [50]. Bone formation and reabsorption have long been identified as a balance between osteoclast and osteoblast activity. More recently, however, osteocytes, the cell of mature bone, have been identified as controlling downstream signal transduction [51]. Osteocytes express the glycoprotein sclerostin, which is suggested to cause osteoblast inhibition and subsequent decrease in bone formation [52]. Sclerostin expression is related to weight bearing activity levels [53], making sclerostin inhibition a potential pharmacologic target and demonstrating another benefit of increased activity and early mobilization among the critically injured. In addition to molecular signaling within the bone, the bone is richly innervated and subject to influence from both the hormonal system and the nervous system. Osteocytes independently express receptors for most neuronally-derived hormones, such as glutamate, calcitonin-related gene peptide, and vasoactive intestinal peptide. Current research is focusing on the complex interactions between the brain and skeletal systems in hopes of finding treatments to increase the strength and healing of bone [54].

Clinically, attention must be paid both to frailty and bone age when considering geriatric patients. While some pharmacologic treatments for sarcopenia and osteoporosis may show promise, the best treatment for musculoskeletal senescence is prevention with increased weight bearing activity and specific training programs [55•]. Resistance training in particular provides increases in both muscle and bone mass in the elderly [56].


In summary, the effects of aging on organ physiology are complex and vary by organ system and tissue type. As basic and clinical science continue to improve our understanding of these changes, we can better apply our knowledge to a variety of clinical scenarios, including a better understanding of the host response to trauma at an older age. With Olympic athletes now winning medals in their 30s and 40s, decades later than previously thought possible, it is likely that the inevitable physiologic changes associated with ageing may be forestalled. Continued better understanding of these processes offers promise for an improvement in treatments of the elderly who suffer traumatic injury.


Compliance with Ethical Standards

Conflict of Interest

Drs. Bonne and Livingston declare no conflicts of interest relevant to this manuscript.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    The Department of Health and Human Services, Administration on Aging. Projected future growth of the older population. Accessed July 20, 2016.
  2. 2.
    Caterino JM, Valasek T, Werman HA. Identification of an age cutoff for increased mortality in patients with elderly trauma. Am J Emerg Med. 2010;28:151–8.CrossRefPubMedGoogle Scholar
  3. 3.
    Holliday R. Aging is no longer an unsolved problem in biology. Ann N Y Acad Sci. 2006;1067:1–9.CrossRefPubMedGoogle Scholar
  4. 4.
    ••Rossi DJ, Bryder D, Seita J, Nussenzweig A, Hoeijmakers J, Weissman IL. Deficiencies in DNA damage repair limit the function of haematopoietic stem cells with age. Nature. 2007;447:725–9. This paper discusses the DNA repair mechanisms with aging in the hematopoietic system.CrossRefPubMedGoogle Scholar
  5. 5.
    Mather KA, Jorm AF, Parslow RA, Christensen H. Is telomere length a biomarker of aging? A review. J Gerontol A Biol Sci Med Sci. 2011;66(2):202–13.CrossRefPubMedGoogle Scholar
  6. 6.
    Ishikawa N, Nakamura K, Izumiyama-Shimomura N, Aida J, Matsuda Y, Arai T, et al. Changes of telomere status with aging: an update. Gerontol Int. 2016;16 Suppl 1:30–42.CrossRefGoogle Scholar
  7. 7.
    ••Townsley DM, Dumitriu B, Liu D, Biancotto A, Weinstein B, Chen C, et al. Danazol treatment for telomere diseases. N Engl J Med. 2016;374:1922–31. This paper highlights the importance of danazol as a potential treatment for disease associated with aging.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Shalev I, Belsky J. Early-life stress and reproductive cost: a two -hit developmental model of accelerated aging? Med Hypotheses. 2016;90:41–7.CrossRefPubMedGoogle Scholar
  9. 9.
    •Rundberg Nilsson A, Soneji S, Adolfsson S, Bryder D, Pronk CJ. Human and murine hematopoietic stem cell aging is associated with functional impairments and intrinsic megakaryocytic/erythroid bias. PLoS One. 2016;11(7):e0158369. This paper describes changes in balance in downstream erythroid potentiation with aging.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Rossi DJ, Bryder D, Zahn JM, Ahlenius H, Sonu R, Wagers AJ, et al. Cell intrinsic alterations underlie hematopoietic stem cell aging. Proc Natl Acad Sci U S A. 2005;102:9194–9.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Gruver AL, Hudson LL, Sempowski GD. Immunosenescence of aging. J Pathol. 2007;211:144–56.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Prince M et al. The global prevalence of dementia: a systematic review and metaanalysis. Alzheimers Dement. 2013;9(1):63–75.CrossRefPubMedGoogle Scholar
  13. 13.
    Foster CM, Picklesimer ME, Mulligan NW, Giovanello KS. The effect of age on relational encoding as revealed by hippocampal functional connectivity. Neurobiol Learn Mem. 2016;134 Pt A:5–14.CrossRefPubMedGoogle Scholar
  14. 14.
    Filippini F, Hayek T, Aviram M, Keidar S, Rodella LF, Coleman R, et al. Apolipoprotein E and its role in aging and survival. Exp Gerontol. 2010;45(2):149–57.CrossRefPubMedGoogle Scholar
  15. 15.
    Neuner SM, Garfinkel BP, Wilmott LA, Ignatowska-Jankowska BM, Citri A, Orly J, et al. Systems genetics identifies Hp1bp3 as a novel modulator of cognitive aging. Neurobiol Aging. 2016;46:58–67.CrossRefPubMedGoogle Scholar
  16. 16.
    •Jackson PA, Pialoux V, Corbett D, Drogos L, Erickson KI, Eskes GA, et al. Promoting brain health through exercise and diet in older adults: a physiological perspective. J Physiol. 2016;594(16):4485–98. This paper describes preventative measures to belay the effects of aging on the brain.CrossRefPubMedGoogle Scholar
  17. 17.
    Tyndall AV, Davenport MH, Wilson BJ, Burek GM, Arsenault-Lapierre G, Haley E, et al. The brain-in-motion study: effect of a 6-month aerobic exercise intervention on cerebrovascular regulation and cognitive function in older adults. BMC Geriatr. 2013;13:21.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    McGuinness B, Todd S, Passmore P, Bullock R. Blood pressure lowering in patients without prior cerebrovascular disease for prevention of cognitive impairment and dementia. Cochrane Database Syst Rev. 2009;4:CD004034.Google Scholar
  19. 19.
    Koga S, Dickson DW, Bieniek KF. Chronic traumatic encephalopathy pathology in multiple system atrophy. J Neuropathol Exp Neurol. 2016;75:963–70.CrossRefPubMedGoogle Scholar
  20. 20.
    Zalewski CK. Aging of the human vestibular system. Semin Hear. 2015;36(3):175–96.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Baloh RW, Honrubia V, Jacobson K. Benign positional vertigo: clinical and oculographic features in 240 cases. Neurology. 1987;37(3):371–8.CrossRefPubMedGoogle Scholar
  22. 22.
    Parnes LS, McClure JA. Free-floating endolymph particles: a new operative finding during posterior semicircular canal occlusion. Laryngoscope. 1992;102(9):988–92.CrossRefPubMedGoogle Scholar
  23. 23.
    Rauch SD, Velazquez-Villaseñor L, Dimitri PS, Merchant SN. Decreasing hair cell counts in aging humans. Ann N Y Acad Sci. 2001;942:220–7.CrossRefPubMedGoogle Scholar
  24. 24.
    Iwasaki S, Smulders YE, Burgess AM, McGarvie LA, Macdougall HG, Halmagyi GM, et al. Ocular vestibular evoked myogenic potentials to bone conducted vibration of the midline forehead at Fz in healthy subjects. Clin Neurophysiol. 2008;119(9):2135–47.CrossRefPubMedGoogle Scholar
  25. 25.
    Agrawal Y, Zuniga MG, Davalos-Bichara M, Schubert MC, Walston JD, Hughes J, et al. Decline in semicircular canal and otolith function with age. Otol Neurotol. 2012;33(5):832–9.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Mattace-Raso FU, van den Meiracker AH, Bos WJ, van der Cammen TJ, Westerhof BE, Elias-Smale S, et al. Arterial stiffness, cardiovagal baroreflex sensitivity and postural blood pressure changes in older adults: the Rotterdam Study. J Hypertens. 2007;25:1421–6.CrossRefPubMedGoogle Scholar
  27. 27.
    Swierblewska E, Hering D, Kara T, Kunicka K, Kruszewski P, Bieniaszewski L, et al. An independent relationship between muscle sympathetic nerve activity and pulse wave velocity in normal humans. J Hypertens. 2010;28:979–84.CrossRefPubMedGoogle Scholar
  28. 28.
    Lind L, Berglund L, Larsson A, Sundström J. Endothelial function in resistance and conduit arteries and 5-year risk of cardiovascular disease. Circulation. 2011;123:1545–51.CrossRefPubMedGoogle Scholar
  29. 29.
    •Parikh JD, Hollingsworth KG, Wallace D, Blamire AM, MacGowan GA. Normal age-related changes in left ventricular function: role of afterload and subendocardial dysfunction. Int J Cardiol. 2016;223:306–12. This paper describes subendocardial dysfunction and changes in cardiac output in aging adults.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Forman DE, Alexander KP. Frailty: a vital sign for older adults with cardiovascular disease. Can J Cardiol. 2016; (16)30127-1.Google Scholar
  31. 31.
    Anton SD, Woods AJ, Ashizawac T, et al. Successful aging: advancing the science of physical independence in older adults. Ageing Res Rev. 2015;24(9):304–27.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Dawson A, Dennison E. Measuring the musculoskeletal aging phenotype. Maturitas 2016.Google Scholar
  33. 33.
    Goodman CA, Hornberger TA, Robling AG. Bone and skeletal muscle: key players in mechanotransduction and potential overlapping mechanisms. Bone. 2015;80:24–36.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Budui SL, Rossi AP, Zamboni M. The pathogenetic bases of sarcopenia. Clin Cases Miner Bone Metab. 2015;12(91):22–6.PubMedPubMedCentralGoogle Scholar
  35. 35.
    Reilly BD, Franklin CE. Prevention of muscle wasting and osteoporosis: the value of examining novel animal models. J Exp Biol. 2016;219:2582–95.CrossRefPubMedGoogle Scholar
  36. 36.
    Talbert EE, Smuder AJ, Min K, Kwon OS, Szeto HH, Powers SK. Immobilization-induced activation of key proteolytic systems in skeletal muscles is prevented by a mitochondria-targeted antioxidant. J Appl Physiol. 2013;115:529–38.CrossRefPubMedGoogle Scholar
  37. 37.
    O’Connor RS, Pavlath GK, McCarthy JJ, Esser KA. Last word on point: counterpoint: satellite cell addition is/is not obligatory for skeletal muscle hypertrophy. J Appl Physiol. 2007;103:1107.CrossRefPubMedGoogle Scholar
  38. 38.
    ••Bruusgaard JC, Johansen IB, Egner IM, Rana ZA, Gundersen K. Myonuclei acquired by overload exercise precede hypertrophy and are not lost on detraining. Proc Natl Acad Sci U S A. 2010;107:15111–6. This paper describes a new paradigm for our understanding of muscle hypertrophy and atrophy.CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Gundersen K. Muscle memory and a new cellular model for muscle atrophy and hypertrophy. J Exp Biol. 2016;219:235–42.CrossRefPubMedGoogle Scholar
  40. 40.
    Glass DJ. Skeletal muscle hypertrophy and atrophy signaling pathways. Int J Biochem Cell Biol. 2005;37:1974–84.CrossRefPubMedGoogle Scholar
  41. 41.
    Cohen S, Nathan JA, Goldberg AL. Muscle wasting in disease: molecular mechanisms and promising therapies. Nat Rev Drug Discov. 2015;14(1):58–74.CrossRefPubMedGoogle Scholar
  42. 42.
    Levine S et al. Rapid disuse atrophy of diaphragm fibers in mechanically ventilated humans. N Engl J Med. 2008;358:1327–35.CrossRefPubMedGoogle Scholar
  43. 43.
    Helliwell TR et al. Muscle fibre atrophy in critically ill patients is associated with the loss of myosin filaments and the presence of lysosomal enzymes and ubiquitin. Neuropathol Appl Neurobiol. 1998;24:507–17.CrossRefPubMedGoogle Scholar
  44. 44.
    •Sheetz KH, Waits SA, Terjimanian MN, et al. Cost of major surgery in the sarcopenic patient. J Am Coll Surg. 2013;217(5):813–8. This paper describes the clinical effects of sarcopenia on patients requiring surgery in old age.CrossRefPubMedGoogle Scholar
  45. 45.
    Please provide complete bibliographic details for this referenceGoogle Scholar
  46. 46.
    Ibebunjo C et al. Genomic and proteomic profiling reveals reduced mitochondrial function and disruption of the neuromuscular junction driving rat sarcopenia. Mol Cell Biol. 2013;33:194–212.CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Brill KT et al. Single and combined effects of growth hormone and testosterone administration on measures of body composition, physical performance, mood, sexual function, bone turnover, and muscle gene expression in healthy older men. J Clin Endocrinol Metab. 2002;87:5649–57.CrossRefPubMedGoogle Scholar
  48. 48.
    Siriett V et al. Antagonism of myostatin enhances muscle regeneration during sarcopenia. Mol Ther. 2007;15:1463–70.CrossRefPubMedGoogle Scholar
  49. 49.
    Szulc P, Delmas PD. Bone loss in elderly men: increased endosteal bone loss and stable periosteal apposition: the prospective MINOS study. Osteoporos Int. 2007;18(4):495–503.CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Drake MT, Clarke BL, Lewiecki EM. The pathophysiology and treatment of osteoporosis. Clin Ther. 2015;37(8):1837–50.CrossRefPubMedGoogle Scholar
  51. 51.
    Santos A, Bakker AD, Klein-Nulend J. The role of osteocytes in bone mechanotransduction. Osteoporos Int. 2009;20:1027–31.CrossRefPubMedGoogle Scholar
  52. 52.
    Baron R, Rawadi G. Minireview: targeting the Wnt/beta-catenin pathway to regulate bone formation in the adult skeleton. Endocrinology. 2007;148:2635–43.CrossRefPubMedGoogle Scholar
  53. 53.
    Spatz JM, Ellman R, Cloutier AM, et al. Sclerostin antibody inhibits skeletal deterioration due to reduced mechanical loading. J Bone Miner Res. 2013;28:865–74.CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Masi L. Crosstalk between the brain and bone. Clin Cases Miner Bone Metab. 2012;9:13–6.PubMedPubMedCentralGoogle Scholar
  55. 55.
    •Gómez-Cabello A, Ara I, González-Agüero A, Casajús JA, Vicente-Rodríguez G. Effects of training on bone mass in older adults: a systematic review. Sports Med. 2012;42(4):301–25. This paper describes preventative measures to belay the effects of aging on the musculoskeletal system.CrossRefPubMedGoogle Scholar
  56. 56.
    English KL, Loehr JA, Lee SMC, Smith SM. Early-phase musculoskeletal adaptations to different levels of eccentric resistance after 8 weeks of lower body training. Eur J Appl Physiol. 2014;114:2263–80.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG 2016

Authors and Affiliations

  1. 1.Division of Trauma and Surgical Critical CareRutgers-New Jersey Medical SchoolNewarkUSA

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