The majority of studies for all the systems provide some important findings regarding the role of chronological age (including age of SCI onset) and YPI, but there is still lack of clarity on how all of these factors affect (individually and in combination) the individual living with SCI over time, and further work is needed to determine if SCI is indeed a model for premature aging.  It appears that the field of aging with SCI has yet to make significant advances since many of the issues and questions raised over 15 years ago (Whiteneck et al. 1993) are still relevant today. 

In general, longitudinal designs are the preferred method for investigating aging, but a number of longitudinal aging-related studies of SCI are limited in scope and quality due to several methodological issues (Krause 2007).  One limitation with longitudinal research designs are problems with retaining sufficient sample size over many years to observe long term changes with aging.  Problems with attrition lead to another type of cohort effect, namely survivor effects.  Survivor effects describe those individuals who may have outlived other members in their cohort due to some unusual advantage (e.g. environmental, physiological, Adkins 2001).  Persons who remain in longitudinal studies often represent those who are healthier, wealthier, and better educated whereas persons with poorer functioning drop-out or have died.  Another limitation of longitudinal designs is the possibility that data collected at an earlier time point may become obsolete due to advances or changes in measurement.  Longitudinal research is also considerably more resource intensive than cross-sectional studies in terms of cost and time.

Despite the challenges associated with longitudinal research, gaining an understanding of what changes a person with SCI may undergo over time is important to identify potential problems that can be anticipated and perhaps prevented in some cases.  This in turn may contribute to continued levels of maximum independence and overall well-being.  The field of aging with SCI has made some tremendous strides forward, but the dearth of knowledge in some areas highlights research opportunities that will help to resolve current challenges and more importantly provide information to fill many existing gaps.   

There is Level 4 evidence (Picklesimer et al. 2010; Frisbie et al. 2010; Savic et al. 2010) that the mortality rate post-SCI over a 10-year period may be 15.5% to 25.8%.

• There is Level 4 evidence (Frisbie 2010) and Level 5 evidence (Samsa et al. 1993) that the causes of death post-SCI are beginning to approximate those of the general population.

• There is Level 5 evidence from an observational study (Samsa et al. 1993) that life expectancy for males with SCI is lower than the general male population.
• There is Level 5 evidence from an observational study (Samsa et al. 1993) that persons who were injured at a younger age (SCI onset approximately < 30 years) will have a longer life expectancy than persons injured at an older age (SCI onset approximately > 30 years).
• There is Level 5 evidence from an observational study (Samsa et al. 1993) that causes of death post-SCI are beginning to approximate those of the general population.
• There is Level 5 evidence from a cross-sectional study (Bauman & Spungen 2001) that plasma homocysteine levels are higher in persons with SCI compared to the AB population, with the greatest discrepancy in older adults with SCI (> 50 years).
• There is Level 5 evidence from seven cross-sectional studies (Zlotolow et al. 1992; Huang et al. 1993; Bauman and Spungen 1994; Bauman et al. 1996; Huang et al. 1998; Bauman et al. 1999; Demirel et al. 2001; Liang et al. 2007; Wang et al. 2007) that abnormal lipid profiles after SCI may contribute to the development of cardiovascular disease.
• There is Level 4 evidence (Shiba et al. 2010) that physical capacity can be maintained long-term in male athletes with SCI.
• There is Level 4 evidence (Apstein & George 1998) that total cholesterol (TC), total glycerides (TG), and low-density lipoproteins (LDL) increased while LDL/high-density lipoproteins (HDL) ratios decreased for males with tetraplegia and paraplegia from the acute phase until 1 YPI. All lipid profiles were significantly depressed compared to controls.
• There is Level 4 evidence (Apstein & George 1998) that persons with tetraplegia had low HDL and elevated LDL/HDL ratios, which placed them at increased risk for coronary artery disease.
• There is Level 5 evidence (Wang et al. 2007) that C-reactive protein levels are higher in males with SCI, which could also account for the decreases in TC, LDL, and HDL. Elevated C-reactive protein levels may also partly explain why persons with SCI are at increased risk for accelerated atherogenesis.
• There is Level 5 evidence (Orakzai et al. 2007) that persons with SCI have greater atherosclerotic burden compared to an AB reference population.
• There is Level 5 evidence from two studies that men with complete paraplegia have an abnormal (absent) heart rate response (Petrofsky & Laymon 2002)
• There is Level 5 evidence that men with complete tetraplegia demonstrate increased blood pressure (Yamamoto et al. 1999).
• There is Level 5 evidence (Tsitouras et al. 1995; Wang et al. 1992; Cheville et al. 1995; Shetty et al. 1999) that there is SCI related lower secretion of testosterone and human growth hormone levels in persons with SCI compared to AB controls.
• There is Level 5 evidence from two studies (Tsitouras et al. 1995; Bauman et al. 1994) that serum IGF-I levels are impaired in persons with SCI compared to the AB population, and may be a sign of premature aging.
• There is Level 5 evidence from three studies (Bauman & Spungen 1994; Jones et al. 2004; Liang et al. 2007) that glucose intolerance is lower after SCI, which may lead to an increased risk for premature diabetes mellitus.
• There is Level 5 evidence (LaVela et al. 2006) that diabetes mellitus occurs prematurely in male veterans with SCI compared to AB veteran controls.

• There is Level 5 evidence (Lewis et al. 2004) that men with SCI have slower plasma-free cortisol responses than AB controls.

  There is Level 4 evidence (DeGroote et al. 2010; Crane et al. 2011) that BMI increases over time in persons with SCI.  

• Seven studies (Nuhlicek et al. 1988; Bauman et al. 1996; Bauman et al. 1999; Spungen et al. 2000; Jones et al. 2003; Jones et al. 2004; Emmons et al. 2011) provide Level 5 evidence that persons with SCI are likely to have higher levels of fat mass, and that age-related declines of lean tissue in males with SCI may occur at a significantly faster rate than the AB population.
• There is Level 5 evidence from one monozygotic twin study (Bauman et al. 2004) that basal and resting energy expenditures are lower in males with SCI compared to their AB twin.

• There is Level 4 evidence that persons with SCI have a prevalence of anemia and hypoalbuminemia (Frisbie 2010), which might serve as markers for infection.

• There is Level 5 evidence (Campagnolo et al. 1994; Campagnolo et al. 1996; Furlan et al. 2006) that the immune function of persons with acute and chronic SCI is compromised compared to the AB population, but there is no influence due to aging.
• There is Level 4 evidence from 9 longitudinal studies (Biering-Sorenson et al. 1990; Garland et al. 1992; Wilmet et al. 1995; de Bruin et al. 2000; Frey-Rindova et al. 2000; Garland et al. 2004; de Bruin et al. 2005; Frotzler et al. 2008; Dudley-Javorski & Shields 2010) and Level 5 evidence from 15 studies (Chow et al. 1996; Szollar et al. 1997a; Szollar et al. 1997b; Szollar et al. 1998; Bauman et al. 1999; Dauty et al. 2000; Kiratli et al. 2000; Garland et al. 2001b; Vlychou et al. 2003; Eser et al. 2004; Giangregorio et al. 2005; Slade et al. 2005; Dudley-Javorski & Shields 2010; Rittweger et al. 2010; Dionyssiotis et al. 2011) that there is a rapid loss of bone in the hip and lower extremities following SCI, and that this loss is significantly lower than the AB population.
• There is Level 2 evidence (Frotzler et al. 2008) and Level 5 evidence (Eser et al. 2004) that tibial and femoral bone geometry and density properties reach a new steady-state within 3-8 YPI, with the time frame depending on bone parameter and skeletal site.
• There is Level 5 evidence from three studies (Szollar et al. 1997a; Szollar et al. 1998; Garland et al. 2001b) that older males and females with SCI may not experience as rapid of a decline in bone mass compared to AB controls.
• There is Level 5 evidence from two studies (Bauman et al. 1999; Garland et al. 2001b) that YPI may be more associated with bone loss after SCI than chronological age.
• There is Level 5 evidence (Slade et al. 2005) that there are differences in bone geometric indices and in structural properties in the lower extremities of women with SCI compared to the AB women.
• There is Level 5 evidence from five studies (Finsen et al. 1992; Vaziri et al. 1994; Bauman et al. 1995; Szollar et al. 1998; Dauty et al. 2000) suggesting that there are impaired biochemical and bone markers in persons with SCI compared to AB controls that persons with SCI are at greater risk for fracture due to the premature development of osteoporosis.
• There is Level 2 evidence from a longitudinal study with AB controls (Catz et al. 1992), Level 4 evidence from a longitudinal study (Biering-Sorenson et al. 1990), and Level 5 evidence from five studies (Chow et al. 1996; Szollar et al. 1997a; Szollar et al. 1997b; Szollar et al. 1998; Garland et al. 2001b) that premature aging does not occur in the lumbar spine after SCI. The possibility that the lumbar spine becomes the primary weight bearing region, along with immobilization, may serve to protect age-related bone loss changes to this region.
• There is Level 5 evidence (Amsters & Nitz 2006) that persons with SCI, regardless of age or YPI, had increased thoracic kyphosis compared to AB controls.
• There is Level 5 evidence from two studies (Pentland & Twomey 1994; Petrofsky & Laymon 2002) that decreased hand grip strength does not occur in men with complete paraplegia and that continual wheelchair use may retard this aging process.
• There is Level 5 evidence (Pentland & Twomey 1994) that upper limb pain in males with complete paraplegia who use manual wheelchairs may be attributed to longer YPI and not to chronological age.
• There is Level 2 evidence from two longitudinal studies (Siddall et al. 2003; Jensen et al. 2005) showing that the incidence of shoulder pain increases over time in persons with SCI.
• There is Level 2 evidence from a longitudinal study (Lal 1998) and Level 5 evidence (Kivimaki et al. 2008) that highlights chronological age having an important influence on developing shoulder pain.
• There is Level 4 evidence from two longitudinal studies (Bach & Wang 1994; Berlowitz et al. 2005) and Level 5 evidence from two observational studies (Cahan et al. 1993; Biering-Sorenson & Biering-Sorenson 2001) that SDB as characterized by sleep apnea, oxygen desaturation, and snoring is more prevalent in SCI populations.
• There is Level 4 evidence from two longitudinal studies (Bach & Wang 1994; Berlowitz et al. 2005) support that SDB may either increase or persist with the aging process.
• There is Level 2 evidence from a longitudinal study with AB controls (Loveridge et al. 1992) that seated breathing patterns are compromised immediately post injury but recover over time. As well, persons with tetraplegia do not take deep breaths as often as AB individuals.
• There is Level 4 evidence from a longitudinal study that adults over the age of 50 who are aging with ventilator dependency are at greater risk of death and are less likely to be weaned from their ventilators than younger adults aging with a ventilator (Wicks & Menter 1986).

• There is Level 5 evidence that respiratory function is impaired compared to AB controls (Ovechkin et al. 2010; Tamplin et al. 2011), and that persons with cervical SCI have similar airway inflammatory responses as mild asthmatics (Radulovic et al. 2010).

• There is Level 4 evidence (Putzke et al. 2002a; Siddall et al. 2003; Rintala et al. 2004; Jensen et al. 2005) that the early onset of SCI-related pain is likely to be maintained over time, with some evidence indicating that the degree of interference experienced might be impacted by age of onset (Jensen et al. 2005).
• There is Level 2 evidence indicating that males with SCI have higher levels of a collagen metabolite, glu-gal Hyl, than AB controls (Rodriguez & Claus-Walker 1984).
• There is Level 4 evidence (Rodriguez & Garber 1994) that increased excretions of glu-gal Hyl is significantly associated with development of pressure ulcers in males with SCI.
• There is Level 2 evidence (Vaziri et al. 1995) suggesting that plasma fibronectin, as an indicator of wound healing, may rise in SCI male patients with fast healing ulcers but not in SCI patients with poor healing ulcers.

• There is Level 5 evidence that the biomechanical skin properties are significantly influenced by sympathetic paralysis rather than somatic sensory paralysis.  Furthermore, in men with complete SCI, YPI may be the influential factor on the biomechanical properties of the skin (Park et al. 2011).  

• There is Level 4 evidence (Viera et al. 1986; DeWire et al. 1992; MacDiarmid et al. 1995; Sekar et al. 1997) that there are no differences in renal functioning up to 4 YPI using various bladder management techniques with some decline occurring beyond that time.
• There is Level 4 evidence (Lamid et al. 1988) that repeated episodes of vesicoureteral reflux can cause kidney damage as early as four YPI in some persons with SCI.
• There is Level 4 evidence (Sekar et al. 1997) that renal plasma flow declines until 10 YPI after SCI, at which time, a slight reversal occurs.
• There is Level 5 evidence (Kuhlemeier et al. 1984) that suggests age of SCI onset may be an important factor related to renal function, with persons with SCI who are under 20 and older than 50 having comparable renal function to AB controls, whereas persons between those ages have impaired functioning compared to the general population.
• There is Level 5 evidence from six studies (Konety et al. 2000; Pramjudi et al. 2002; Pannek et al. 2003; Scott Sr et al. 2003; Alexandrino et al. 2004; Shim et al. 2008) that males with SCI do not appear to be at higher risk for the development of prostate cancer compared to the general population.
• There is Level 5 evidence (Scott Sr et al. 2003) that persons with SCI and prostate cancer have higher levels of prostate serum antigen at diagnosis and cancer that was more advanced and metastatic than AB controls with prostate cancer.

• There is Level 5 evidence (Alexandrino et al. 2011) that men with SCI have lower seminal zinc concentrations, as an indicator of prostate function, than AB controls.

  There is Level 3 evidence (Kalpakjian et al. 2010) that women with SCI experience menopause similarly to AB controls.

• There is Level 5 evidence (Lynch et al. 2000) demonstrating a deterioration in bowel continence with increasing age in an AB population but no change with age in persons with SCI.
• There is Level 4 evidence (Faaborg et al. 2008) suggesting persons with SCI do incur an increase in constipation-related symptoms and decrease in fecal incontincence over time.

• There is Level 5 evidence that high amplitude propagating contractions (HAPC) are absent in persons with SCI compared to AB controls (Ancha et al. 2010).

  There is Level 4 evidence (Faaborg et al. 2011) that gastrointestinal transit times and colonic dimensions do not change over time in persons with SCI.

• There is Level 5 evidence from three studies (Menardo et al. 1987; Krogh et al. 2000; Emmanuel et al. 2009) that level of injury, and not necessarily age or YPI, plays a primary role in the extent of bowel dysfunction.
• There is Level 4 evidence from four longitudinal studies (Bushnik 2002; Bushnik & Charlifue 2005; Krause & Broderick 2005; Krause & Coker 2006) that changes in environmental factors over time (i.e. economics; technology) may influence QoL in persons with SCI rather than the aging process per se.
• There is Level 4 evidence from two longitudinal studies (Charlifue & Gerhart 2004a; Bushnik & Charlifue 2005) that community reintegration declines with age after SCI. However, these changes in community reintegration may be similar as compared to the aging general population.

• There is Level 4 evidence from 6 longitudinal studies (Crewe &Krause 1990; Krause 1992; Krause 1997; Krause 1998; Krause &Broderick 2005; Krause &Coker 2006) that selected domains of life satisfaction change (i.e., social life and sex life decrease, and employment and finances increase)  as one ages with an SCI.  It may be that these changes in satisfaction of certain domains are comparable to changes in the general population.

• There is Level 5 evidence from a cross-sectional study (Kemp & Krause 1999) that age of SCI-onset may be an influential factor on life satisfaction.
• There is Level 4 evidence from one longitudinal studies (Charlifue & Gerhart 2004b) that previous perceptions of life satisfaction are predictive of later perceptions of life satisfaction.
• There is Level 5 evidence from two cross-sectional studies (Kemp & Krause 1999; Barker et al. 2011) that life satisfaction is lower for persons with SCI compared to the general population.
• There is Level 4 evidence from two longitudinal studies (Stensman 1994; Putzke et al. 2002a) that previous reports of pain interference after SCI, irrespective of age, are predictive of later pain interference.
• There is Level 4 evidence from a longitudinal study (Charlifue et al. 1999) that fatigue and the need for physical assistance increases over time with SCI.

• There is level 4 evidence from 10 longitudinal studies that individuals with ≤5 YPI have the potential to improve their QoL (Stensman 1994; Kemp &Krause 1999; Bushnik 2002; Putzke et al. 2002; Bushnik &Charlifue 2005; Krause &Coker 2006; van Koppenhagen et al. 2009; DeVivo &Chen 2011; Kalpakjian et al. 2011; van Leeuwen et al. 2011).

  There is level 4 evidence from 4 longitudinal studies that individuals with longer term SCI (i.e., ≥6 YPI) consistently report high and stable QoL level (Charlifue et al. 1998; Charlifue et al. 1999; Charlifue &Gerhart 2004b; Savic et al. 2010).