Impact of aging on the digestive system related to protein digestion in vivo

“Recently, the INFOGEST consortium, which published a consensus protocol for static in vitro digestion (Brodkorb et al. 2019; Minekus et al. 2014), has published its recommendations for adaptations to be done to the original in vitro model to simulate the aged digestive system (Menard et al. 2023).”

“Recently, the INFOGEST consortium, which published a consensus protocol for static in vitro digestion (Brodkorb et al. 2019; Minekus et al. 2014), has published its recommendations for adaptations to be done to the original in vitro model to simulate the aged digestive system (Menard et al. 2023).”

“This response is reduced with aging, known as “anabolic resistance”, and a higher intake of amino acids is believed to be needed for muscle mass maintenance in the older adult (Bauer et al. 2013).”

“It is already advised by some authorities to increase daily protein intake in older individuals (Deutz et al. 2014).”

“In these subjects, there was no clinical evidence of nitrogen malabsorption according to their nitrogen balance (Boirie, Gachon, et al. 1997).”

“It can be rather extensive and around 30–50% of the intake of the essential amino acids is reported to be catabolized by the small intestine (Wu 1998; Deutz, Bruins, and Soeters 1998).”

“Concrete ways to determine biological age are not defined yet (Klemera and Doubal 2006), resulting in most studies only taking chronological age into account.”

“…due to muscle weakness and heightened pharyngeal and upper esophageal constriction (Tack and Vantrappen 1997; Ortega, Martín, and Clavé 2017; Clavé and Shaker 2015; Muhle et al. 2015), affects the elderly with a prevalence ranging from 13.8 to 70% (Watanabe et al. 2021; Yoshikawa et al.…”

“The number of teeth decreases with age (Müller, Naharro, and Carlsson 2007; Ozturk et al. 2013; Morales-Suárez-Varela et al. 2011) and the prevalence of being edentulous, i.e. lacking all teeth, ranges between 4 and 56% across studies (Table 2(a)) with age ranges of 65–92 years (Choufani et al.…”

“%) and threonine (61%), which was mainly catabolized by the enterocytes (Stoll et al. 1998).”

“…saunders and Friedman 2007; schein et al. 1999; so et al. 2010; viljakainen et al. 2016) increase range in chewing strokes (Feldman et al. 1980; Hatch et al. 2001; Kohyama, Mioche, and Martin 2002; Bessadet et al. 2013; Mishellany-dutour et al. 2008; Peyron et al. 2004; wayler and Chauncey…”

“Proton pump inhibitors, drugs that are often prescribed to older adults, also increase gastric pH (Freedberg, Lebwohl, and Abrams 2014; Scarpignato et al. 2016; Rayner and Horowitz 2013).”

“Also for phenylalanine, splanchnic extraction was 1.6 times higher in elderly subjects (71 ± 2 years) compared to young subjects (30 ± 2 years) (Volpi et al. 1999).”

“However, in combination with atrophic gastritis, atrophy and H. pylori infection, gastric acid secretion has been shown to decrease and gastric pH to increase upon aging (>65 years) (Haruma et al. 2000; Baik and Russell 1999; Nakamura, Ogoshi, and Makuuchi 2006; Iijima et al. 2004).”

“With a similar experimental methodology, protein metabolism was studied using intrinsically 13 C-Leu labeled whey protein and casein protein in older and younger participants (Dangin et al. 2003).”

“…considering 18 randomized controlled trials using this approach (Gorissen et al. 2020) included four studies investigating the effect of age with a total of 82 young and 83 older adults (Gorissen et al. 2014; Koopman et al. 2009; Pennings et al. 2011; Groen et al. 2016; Gorissen et al. 2020).”

“To compare these rat studies to human age categories; 5 wks old rats are considered to be infants, whereas 20 months for rats represent approximately 50 human years (Andreollo et al. 2012; Sengupta 2013).”

“For the gastric phase, we concluded no difference in fasting pH independent of infections in the older adults, while it is increased 0.7 points in the adapted protocol, because of the slower rate of returning to fasting pH after feeding in older adults was taken into account (Russell et al. 1993).”

“A smaller particle size, and thus an increased surface area, has been shown to result in an increase in protein digestion of up to 10% in vitro and in pigs (Healy et al. 1994; Lyu et al. 2022; Wondra et al. 1995; Zahir, Fogliano, and Capuano 2018).”

“Interstitial cells of Cajal are the cells that initiate the membrane potential (Costa, Brookes, and Hennig 2000; Greenwood-Van Meerveld, Johnson, and Grundy 2017).”

“Until approximately 25 years of age, bite force increases with age, while afterwards, it decreases, resulting in lower muscle activity per chew for the elderly (Bakke et al. 1990; Newton et al. 1993; Nguyen et al. 2018; Palinkas et al. 2010).”

“It still needs more validation, especially when specific populations are studied (Santos-Sánchez et al. 2024; Sousa et al. 2023; Bohn et al. 2018).”

“These reviews have varied in their specific focus, for example on malnutrition prevention (Rémond et al. 2015), drug absorption (Stillhart et al. 2020; Khan and Roberts 2018), diseases (Grassi et al. 2011) and motility (Gidwaney, Bajpai, and Chokhavatia 2016; O’Mahony, O’Leary, and Quigley 2002).”

“…(Åstrøm et al. 2019; Bakker et al. 2020; Fernandes et al. 2021; Glazar et al. 2010; Hahnel et al. 2014; Hochberg et al. 1998; Johansson et al. 2012; nederfors et al. 1997; ohara et al. 2011; ramsay et al. 2015; saunders and Friedman 2007; schein et al. 1999; so et al. 2010; viljakainen et al.…”

“These reviews have varied in their specific focus, for example on malnutrition prevention (Rémond et al. 2015), drug absorption (Stillhart et al. 2020; Khan and Roberts 2018), diseases (Grassi et al. 2011) and motility (Gidwaney, Bajpai, and Chokhavatia 2016; O’Mahony, O’Leary, and Quigley 2002).”

“Bite force is related to muscle mass and function in the mouth (Mioche, Bourdiol, and Peyron 2004; Peyron et al. 2004; Woda, Mishellany, et al. 2006).”

“…Makuuchi 2006; Pilotto et al. 1994; shih et al. 2003; russell et al. 1993; Feldman et al. 1996 range prolonged emptying time (Brogna et al. 1999; Clarkston et al. 1997; di Francesco et al. 2005; evans et al. 1981; Kao et al. 1994; nakae et al. 1999; Pham et al. 2020; wegener et al. 1988 (Fikry…”

“…considering 18 randomized controlled trials using this approach (Gorissen et al. 2020) included four studies investigating the effect of age with a total of 82 young and 83 older adults (Gorissen et al. 2014; Koopman et al. 2009; Pennings et al. 2011; Groen et al. 2016; Gorissen et al. 2020).”

“…1997; Ortega, Martín, and Clavé 2017; Clavé and Shaker 2015; Muhle et al. 2015), affects the elderly with a prevalence ranging from 13.8 to 70% (Watanabe et al. 2021; Yoshikawa et al. 2005; Smith et al. 2006; Nilsson et al. 1996; Leder and Suiter 2009; Kawashima, Motohashi, and Fujishima 2004).”

“Until approximately 25 years of age, bite force increases with age, while afterwards, it decreases, resulting in lower muscle activity per chew for the elderly (Bakke et al. 1990; Newton et al. 1993; Nguyen et al. 2018; Palinkas et al. 2010).”

“…al. 2000; Hurwitz et al. 1997; iijima et al. 2004; nakamura, ogoshi, and Makuuchi 2006; Pilotto et al. 1994; shih et al. 2003; russell et al. 1993; Feldman et al. 1996 range prolonged emptying time (Brogna et al. 1999; Clarkston et al. 1997; di Francesco et al. 2005; evans et al. 1981; Kao et al.…”

“…(Feldman et al. 1980; Hatch et al. 2001; Kohyama, Mioche, and Martin 2002; Bessadet et al. 2013; Mishellany-dutour et al. 2008; Peyron et al. 2004; wayler and Chauncey 1983; aguayo-Mendoza et al. 2020; (Grande et al. 1999; ren et al. 1995; Bardan et al. 2000; Kern et al. 1999; ren et al. 2000;…”

“…et al. 2014; Hochberg et al. 1998; Johansson et al. 2012; nederfors et al. 1997; ohara et al. 2011; ramsay et al. 2015; saunders and Friedman 2007; schein et al. 1999; so et al. 2010; viljakainen et al. 2016) increase range in chewing strokes (Feldman et al. 1980; Hatch et al. 2001; Kohyama,…”

“…characterized by impaired swallowing due to muscle weakness and heightened pharyngeal and upper esophageal constriction (Tack and Vantrappen 1997; Ortega, Martín, and Clavé 2017; Clavé and Shaker 2015; Muhle et al. 2015), affects the elderly with a prevalence ranging from 13.8 to 70% (Watanabe…”

“Cholecystokinin (CCK) is one hormone that signals satiation and is increased in older adults (de Boer, Ter Horst, and Lorist 2013; Di Francesco et al. 2005; Nakae et al. 1999; Serra-Prat et al. 2013; Sandström and El-Salhy 1999; MacIntosh et al. 1999).”

“Nevertheless, some studies did not find an effect of aging on gastric emptying time (Hellmig et al. 2006; Madsen and Graff 2004; Madsen 1992) or only an age effect on gastric emptying for liquid foods (Kao et al. 1994) or lipid-rich foods (Nakae et al. 1999).”

“Until approximately 25 years of age, bite force increases with age, while afterwards, it decreases, resulting in lower muscle activity per chew for the elderly (Bakke et al. 1990; Newton et al. 1993; Nguyen et al. 2018; Palinkas et al. 2010).”

“…in chewing strokes (Feldman et al. 1980; Hatch et al. 2001; Kohyama, Mioche, and Martin 2002; Bessadet et al. 2013; Mishellany-dutour et al. 2008; Peyron et al. 2004; wayler and Chauncey 1983; aguayo-Mendoza et al. 2020; (Grande et al. 1999; ren et al. 1995; Bardan et al. 2000; Kern et al. 1999;…”

“…(Kohyama, Mioche, and Martin 2002; Mioche, Bourdiol, and Peyron 2004; Mishellany-Dutour et al. 2008; Bessadet et al. 2013; Aguayo-Mendoza et al. 2020) to allow swallowing of the ingested food (Feldman et al. 1980; Peyron et al. 2004; Mioche, Bourdiol, and Peyron 2004; Woda, Foster, et al. 2006).”

“Sarcopenia is an example of an age-related disease, characterized by a decline in muscle mass and strength (Soenen et al. 2016; Milan and Cameron-Smith 2015).”

“This motility, together with the time in the intestine, are important for digestive enzymes to be able to access nutrients and exert their function (Lentle and Janssen 2008; Lentle and de Loubens 2015).”

“Interstitial cells of Cajal are the cells that initiate the membrane potential (Costa, Brookes, and Hennig 2000; Greenwood-Van Meerveld, Johnson, and Grundy 2017).”

“Proton pump inhibitors, drugs that are often prescribed to older adults, also increase gastric pH (Freedberg, Lebwohl, and Abrams 2014; Scarpignato et al. 2016; Rayner and Horowitz 2013).”

“Current knowledge on the aging digestive system has been reviewed in order to adjust the in vitro models accordingly (Shani-Levi et al. 2017; Lee et al. 2023; Mackie, Mulet-Cabero, and Torcello-Gómez 2020).”

“Nevertheless, some studies did not find an effect of aging on gastric emptying time (Hellmig et al. 2006; Madsen and Graff 2004; Madsen 1992) or only an age effect on gastric emptying for liquid foods (Kao et al. 1994) or lipid-rich foods (Nakae et al. 1999).”

“Immune function is deteriorating in older adults, T-cell proliferation is reduced (69–84 years) (Dillon et al. 2020) and IL-6 production is increased (67–77 years) (Man et al. 2015) with aging.”

“…(Grande et al. 1999; ren et al. 1995; Ferriolli et al. 1998; soergel, Zboralske, and Cryer et al. 1992; Feldman and Cryer 1998; Haruma et al. 2000; Hurwitz et al. 1997; iijima et al. 2004; nakamura, ogoshi, and Makuuchi 2006; Pilotto et al. 1994; shih et al. 2003; russell et al. 1993; Feldman et…”

“It still needs more validation, especially when specific populations are studied (Santos-Sánchez et al. 2024; Sousa et al. 2023; Bohn et al. 2018).”

“…et al. 2000; Kern et al. 1999; ren et al. 2000; shaker et al. 1993; Besanko et al (Grande et al. 1999; ren et al. 1995; Ferriolli et al. 1998; soergel, Zboralske, and Cryer et al. 1992; Feldman and Cryer 1998; Haruma et al. 2000; Hurwitz et al. 1997; iijima et al. 2004; nakamura, ogoshi, and…”

“Nevertheless, some studies did not find an effect of aging on gastric emptying time (Hellmig et al. 2006; Madsen and Graff 2004; Madsen 1992) or only an age effect on gastric emptying for liquid foods (Kao et al. 1994) or lipid-rich foods (Nakae et al. 1999).”

“…et al. 1997; di Francesco et al. 2005; evans et al. 1981; Kao et al. 1994; nakae et al. 1999; Pham et al. 2020; wegener et al. 1988 (Fikry 1968; laugier et al. 1991; vellas et al. 1988) no change enzyme output or pancreatic function 3 204 55 = (Gullo et al. 1986; Gullo et al. 1983; Gullo et”

“Cholecystokinin (CCK) is one hormone that signals satiation and is increased in older adults (de Boer, Ter Horst, and Lorist 2013; Di Francesco et al. 2005; Nakae et al. 1999; Serra-Prat et al. 2013; Sandström and El-Salhy 1999; MacIntosh et al. 1999).”

“…2003; russell et al. 1993; Feldman et al. 1996 range prolonged emptying time (Brogna et al. 1999; Clarkston et al. 1997; di Francesco et al. 2005; evans et al. 1981; Kao et al. 1994; nakae et al. 1999; Pham et al. 2020; wegener et al. 1988 (Fikry 1968; laugier et al. 1991; vellas et al. 1988)…”

“A smaller particle size, and thus an increased surface area, has been shown to result in an increase in protein digestion of up to 10% in vitro and in pigs (Healy et al. 1994; Lyu et al. 2022; Wondra et al. 1995; Zahir, Fogliano, and Capuano 2018).”

“The number of masticatory cycles increases by 13–30% with age (Table 2(a)), so chewing duration increases (Kohyama, Mioche, and Martin 2002; Mioche, Bourdiol, and Peyron 2004; Mishellany-Dutour et al. 2008; Bessadet et al. 2013; Aguayo-Mendoza et al. 2020) to allow swallowing of the ingested food…”

“…wayler and Chauncey 1983; aguayo-Mendoza et al. 2020; (Grande et al. 1999; ren et al. 1995; Bardan et al. 2000; Kern et al. 1999; ren et al. 2000; shaker et al. 1993; Besanko et al (Grande et al. 1999; ren et al. 1995; Ferriolli et al. 1998; soergel, Zboralske, and Cryer et al. 1992; Feldman…”

“Evaluation of protein quality considers the capacity of a protein source to provide indispensable amino acids, which is dependent on amino acid composition and digestibility (Elango, Levesque, et al. 2012; Elango, Ball, and Pencharz 2008).”

“…1993; Besanko et al (Grande et al. 1999; ren et al. 1995; Ferriolli et al. 1998; soergel, Zboralske, and Cryer et al. 1992; Feldman and Cryer 1998; Haruma et al. 2000; Hurwitz et al. 1997; iijima et al. 2004; nakamura, ogoshi, and Makuuchi 2006; Pilotto et al. 1994; shih et al. 2003; russell et…”

“Bite force is related to muscle mass and function in the mouth (Mioche, Bourdiol, and Peyron 2004; Peyron et al. 2004; Woda, Mishellany, et al. 2006).”

“…Morales-Suárez-Varela et al. 2011) and the prevalence of being edentulous, i.e. lacking all teeth, ranges between 4 and 56% across studies (Table 2(a)) with age ranges of 65–92 years (Choufani et al. 2020; Ikebe et al. 2007; Saunders and Friedman 2007; Shariff et al. 2018; Ramsay et al. 2015).”

“Current knowledge on the aging digestive system has been reviewed in order to adjust the in vitro models accordingly (Shani-Levi et al. 2017; Lee et al. 2023; Mackie, Mulet-Cabero, and Torcello-Gómez 2020).”

“Postprandial protein synthesis was found to be lower in denture wearers than in dentated subjects (30 and 48% of the leucine intake respectively) (Rémond et al. 2007).”

“…considering 18 randomized controlled trials using this approach (Gorissen et al. 2020) included four studies investigating the effect of age with a total of 82 young and 83 older adults (Gorissen et al. 2014; Koopman et al. 2009; Pennings et al. 2011; Groen et al. 2016; Gorissen et al. 2020).”

“This first relevant animal study identified, compared fecal nitrogen digestibility of fifteen protein sources between young (5 wks) and old (20 months) rats (Gilani and Sepehr 2003).”

“Little nutritionally relevant absorption takes place in the colon, all bioavail-able protein fragments are absorbed by the end of the small intestine (terminal ileum) (van der Wielen, Moughan, and Mensink 2017).”

“…cycles increases by 13–30% with age (Table 2(a)), so chewing duration increases (Kohyama, Mioche, and Martin 2002; Mioche, Bourdiol, and Peyron 2004; Mishellany-Dutour et al. 2008; Bessadet et al. 2013; Aguayo-Mendoza et al. 2020) to allow swallowing of the ingested food (Feldman et al. 1980;…”

“…and Martin 2002; Bessadet et al. 2013; Mishellany-dutour et al. 2008; Peyron et al. 2004; wayler and Chauncey 1983; aguayo-Mendoza et al. 2020; (Grande et al. 1999; ren et al. 1995; Bardan et al. 2000; Kern et al. 1999; ren et al. 2000; shaker et al. 1993; Besanko et al (Grande et al. 1999;…”

“The digestion of ingested protein is influenced by the capacity of the digestive system (Gorissen et al. 2020) and has consequences for subsequent amino acid absorption, splanchnic retention, muscle perfusion, amino acid uptake in muscle and ultimately activation of muscle protein synthesis.”

“The majority of studies showed that gastric emptying is delayed (Giezenaar et al. 2017; Moore et al. 1983; O’Donovan et al. 2005; Rayner et al. 2000; Shimamoto et al. 2002) with between 11 and 69% prolongation of emptying time in older adults (mean range 65–76 years old) compared to younger adults…”

“Concerning structure, there is increased fibrosis in the pancreas (Saini et al. 2015; Löhr et al. 2018) and increased fat content (Yang et al. 2019; Moin et al. 2020).”

“…1997; Ortega, Martín, and Clavé 2017; Clavé and Shaker 2015; Muhle et al. 2015), affects the elderly with a prevalence ranging from 13.8 to 70% (Watanabe et al. 2021; Yoshikawa et al. 2005; Smith et al. 2006; Nilsson et al. 1996; Leder and Suiter 2009; Kawashima, Motohashi, and Fujishima 2004).”

“Optimal protein intake provides adequate quantities of nitrogen and indispensable amino acids to meet requirements (Elango, Ball, and Pencharz 2012; Lee et al. 2016).”

“This was observed during fasting (Anuras and Sutherland 1984; Fischer and Fadda 2016), and after consumption of a meal (Kagaya et al. 1997; Husebye and Engedal 1992) and has been commented on by others (Brogna et al. 1999; Clarkston et al. 1997; O’Mahony, O’Leary, and Quigley 2002).”

“Digestion starts in the mouth, where food is mixed with saliva that contains amylase as a digestive enzyme, although not specific for protein degradation (Boland 2016).”

“…et al. 1994; shih et al. 2003; russell et al. 1993; Feldman et al. 1996 range prolonged emptying time (Brogna et al. 1999; Clarkston et al. 1997; di Francesco et al. 2005; evans et al. 1981; Kao et al. 1994; nakae et al. 1999; Pham et al. 2020; wegener et al. 1988 (Fikry 1968; laugier et al.…”

“Small bowel bacterial overgrowth increases with aging (18–80 years) along with concomitant diseases (Mitsui et al. 2006; Leite et al. 2022; Lewis et al. 1999; Parlesak et al. 2003).”

“In fact, some studies have even shown an increased acidity with age (Cryer et al. 1992; Feldman and Cryer 1998; Russell et al. 1993).”

“These reviews have varied in their specific focus, for example on malnutrition prevention (Rémond et al. 2015), drug absorption (Stillhart et al. 2020; Khan and Roberts 2018), diseases (Grassi et al. 2011) and motility (Gidwaney, Bajpai, and Chokhavatia 2016; O’Mahony, O’Leary, and Quigley 2002).”

“…1997; Ortega, Martín, and Clavé 2017; Clavé and Shaker 2015; Muhle et al. 2015), affects the elderly with a prevalence ranging from 13.8 to 70% (Watanabe et al. 2021; Yoshikawa et al. 2005; Smith et al. 2006; Nilsson et al. 1996; Leder and Suiter 2009; Kawashima, Motohashi, and Fujishima 2004).”

“Recently, the INFOGEST consortium, which published a consensus protocol for static in vitro digestion (Brodkorb et al. 2019; Minekus et al. 2014), has published its recommendations for adaptations to be done to the original in vitro model to simulate the aged digestive system (Menard et al. 2023).”

“It can be rather extensive and around 30–50% of the intake of the essential amino acids is reported to be catabolized by the small intestine (Wu 1998; Deutz, Bruins, and Soeters 1998).”

“…and Lang 1994; Robbins, Bridges, and Taylor 2006), caused by changed sphincter contractility and pressure (Cock and Omari 2018; Bardan et al. 2000; Besanko et al. 2014), and muscular and neuronal changes (Milosavljevic et al. 2013; Meciano Filho, Carvalho, and de Souza 1995; Iida et al. 2013).”

“Intestinal wall integrity is found to be decreased (Hendriks et al. 2021) and permeability increased with low-grade inflammation present (Valentini et al. 2014), but that result is not consistently found (Saltzman et al. 1995).”

“Prevalence of exocrine pancreatic insufficiency, as measured via fecal elastase-1, increases with age and has been reported to be 11.5% in one study in participants aged 50–75 years (Rothenbacher et al. 2005) and 21.7% in another study with participants aged 60–92 years (Herzig et al. 2011).”

“The enzymatic activity of pepsin is optimal at pH 2, but pepsin still functions up to pH 6 (Salelles, Floury, and Le Feunteun 2021; Campos and Sancho 2003).”

“…1997; Ortega, Martín, and Clavé 2017; Clavé and Shaker 2015; Muhle et al. 2015), affects the elderly with a prevalence ranging from 13.8 to 70% (Watanabe et al. 2021; Yoshikawa et al. 2005; Smith et al. 2006; Nilsson et al. 1996; Leder and Suiter 2009; Kawashima, Motohashi, and Fujishima 2004).”

“Saliva production also decreases with age as studied in participants aged 20–97 years (Smith et al. 2013) and is one of the potential causes of dry mouth (Hochberg et al. 1998; Glazar et al. 2010; Hahnel et al. 2014), which has increased prevalence with age (Johansson et al. 2012; Schein et al.…”

“…and 69% prolongation of emptying time in older adults (mean range 65–76 years old) compared to younger adults (mean range 22–31 years) (Table 2(c)) (Brogna et al. 1999; Clarkston et al. 1997; Di Francesco et al. 2005; Evans et al. 1981; Kao et al. 1994; Nakae et al. 1999; Pham et al. 2020; Wegener…”

“Prevalence range xerostomia (Åstrøm et al. 2019; Bakker et al. 2020; Fernandes et al. 2021; Glazar et al. 2010; Hahnel et al. 2014; Hochberg et al. 1998; Johansson et al. 2012; nederfors et al. 1997; ohara et al. 2011; ramsay et al. 2015; saunders and Friedman 2007; schein et al. 1999; so et al.…”

“…et al. 2008; Peyron et al. 2004; wayler and Chauncey 1983; aguayo-Mendoza et al. 2020; (Grande et al. 1999; ren et al. 1995; Bardan et al. 2000; Kern et al. 1999; ren et al. 2000; shaker et al. 1993; Besanko et al (Grande et al. 1999; ren et al. 1995; Ferriolli et al. 1998; soergel, Zboralske,…”

“…ren et al. 1995; Bardan et al. 2000; Kern et al. 1999; ren et al. 2000; shaker et al. 1993; Besanko et al (Grande et al. 1999; ren et al. 1995; Ferriolli et al. 1998; soergel, Zboralske, and Cryer et al. 1992; Feldman and Cryer 1998; Haruma et al. 2000; Hurwitz et al. 1997; iijima et al.…”

“A smaller particle size, and thus an increased surface area, has been shown to result in an increase in protein digestion of up to 10% in vitro and in pigs (Healy et al. 1994; Lyu et al. 2022; Wondra et al. 1995; Zahir, Fogliano, and Capuano 2018).”

“The majority of studies showed that gastric emptying is delayed (Giezenaar et al. 2017; Moore et al. 1983; O’Donovan et al. 2005; Rayner et al. 2000; Shimamoto et al. 2002) with between 11 and 69% prolongation of emptying time in older adults (mean range 65–76 years old) compared to younger adults…”

“Degeneration of neurons occurs in both the myenteric and submucosal plexus (Bitar et al. 2011).”

“…20–97 years (Smith et al. 2013) and is one of the potential causes of dry mouth (Hochberg et al. 1998; Glazar et al. 2010; Hahnel et al. 2014), which has increased prevalence with age (Johansson et al. 2012; Schein et al. 1999; Bakker et al. 2020; Fernandes et al. 2021; Viljakainen et al. 2016).”

“Cholecystokinin (CCK) is one hormone that signals satiation and is increased in older adults (de Boer, Ter Horst, and Lorist 2013; Di Francesco et al. 2005; Nakae et al. 1999; Serra-Prat et al. 2013; Sandström and El-Salhy 1999; MacIntosh et al. 1999).”

“…Morales-Suárez-Varela et al. 2011) and the prevalence of being edentulous, i.e. lacking all teeth, ranges between 4 and 56% across studies (Table 2(a)) with age ranges of 65–92 years (Choufani et al. 2020; Ikebe et al. 2007; Saunders and Friedman 2007; Shariff et al. 2018; Ramsay et al. 2015).”

“The enzymatic activity of pepsin is optimal at pH 2, but pepsin still functions up to pH 6 (Salelles, Floury, and Le Feunteun 2021; Campos and Sancho 2003).”

“Concerning ileal protein digestibility, the growing rat and growing pig are widely used and are considered suitable models for healthy adults (Deglaire and Moughan 2012; FAO 2014; Hodgkinson et al. 2022).”

“…et al. 1997; di Francesco et al. 2005; evans et al. 1981; Kao et al. 1994; nakae et al. 1999; Pham et al. 2020; wegener et al. 1988 (Fikry 1968; laugier et al. 1991; vellas et al. 1988) no change enzyme output or pancreatic function 3 204 55 = (Gullo et al. 1986; Gullo et al. 1983; Gullo et”

“Biological age quantifies the state of health, considering the physiological reserve and functional status of an individual, while chronological age only represents time passed since birth (Colloca et al. 2020).”

“On the other hand, dogs and humans are only comparable for nitrogen disappearance from the large intestine (Hendriks, van Baal, and Bosch 2012).”

“…1997; Ortega, Martín, and Clavé 2017; Clavé and Shaker 2015; Muhle et al. 2015), affects the elderly with a prevalence ranging from 13.8 to 70% (Watanabe et al. 2021; Yoshikawa et al. 2005; Smith et al. 2006; Nilsson et al. 1996; Leder and Suiter 2009; Kawashima, Motohashi, and Fujishima 2004).”

“However, in combination with atrophic gastritis, atrophy and H. pylori infection, gastric acid secretion has been shown to decrease and gastric pH to increase upon aging (>65 years) (Haruma et al. 2000; Baik and Russell 1999; Nakamura, Ogoshi, and Makuuchi 2006; Iijima et al. 2004).”

“Normal esophageal motility deteriorates with aging (Grande et al. 1999; Shaker and Lang 1994; Robbins, Bridges, and Taylor 2006), caused by changed sphincter contractility and pressure (Cock and Omari 2018; Bardan et al. 2000; Besanko et al. 2014), and muscular and neuronal changes (Milosavljevic…”

“The majority of studies showed that gastric emptying is delayed (Giezenaar et al. 2017; Moore et al. 1983; O’Donovan et al. 2005; Rayner et al. 2000; Shimamoto et al. 2002) with between 11 and 69% prolongation of emptying time in older adults (mean range 65–76 years old) compared to younger adults…”

“These reviews have varied in their specific focus, for example on malnutrition prevention (Rémond et al. 2015), drug absorption (Stillhart et al. 2020; Khan and Roberts 2018), diseases (Grassi et al. 2011) and motility (Gidwaney, Bajpai, and Chokhavatia 2016; O’Mahony, O’Leary, and Quigley 2002).”

“Intestinal wall integrity is found to be decreased (Hendriks et al. 2021) and permeability increased with low-grade inflammation present (Valentini et al. 2014), but that result is not consistently found (Saltzman et al. 1995).”

“In another study, a delayed peak in the curve of plasma amino acids was found after ingestion of a high-protein mixed meal (50 grams of protein) in older adults, which could be indicative of a delayed absorption of amino acids for older adults (Milan et al. 2015).”

“Prevalence of exocrine pancreatic insufficiency, as measured via fecal elastase-1, increases with age and has been reported to be 11.5% in one study in participants aged 50–75 years (Rothenbacher et al. 2005) and 21.7% in another study with participants aged 60–92 years (Herzig et al. 2011).”

“…time (Brogna et al. 1999; Clarkston et al. 1997; di Francesco et al. 2005; evans et al. 1981; Kao et al. 1994; nakae et al. 1999; Pham et al. 2020; wegener et al. 1988 (Fikry 1968; laugier et al. 1991; vellas et al. 1988) no change enzyme output or pancreatic function 3 204 55 = (Gullo et al.…”

“…indicates protein handling, where the bioavailable amino acids are considered to be the proportion of amino acids from dietary protein that reach the peripheral circulation and are available for protein synthesis, which follows after digestion and splanchnic metabolism (Gaudichon and Calvez 2021).”

“…and heightened pharyngeal and upper esophageal constriction (Tack and Vantrappen 1997; Ortega, Martín, and Clavé 2017; Clavé and Shaker 2015; Muhle et al. 2015), affects the elderly with a prevalence ranging from 13.8 to 70% (Watanabe et al. 2021; Yoshikawa et al. 2005; Smith et al. 2006;…”

“The majority of studies showed that gastric emptying is delayed (Giezenaar et al. 2017; Moore et al. 1983; O’Donovan et al. 2005; Rayner et al. 2000; Shimamoto et al. 2002) with between 11 and 69% prolongation of emptying time in older adults (mean range 65–76 years old) compared to younger adults…”

“Additionally, analysis of duodenal biopsies (mean 77.6 versus 37.7 years) showed a significant 15.3% increase in enterocyte apoptosis and that was correlated with a 37.7% increase in enterocyte proliferation, suggesting a high cell turnover in older adults (Ciccocioppo et al. 2002).”

“Dysphagia, characterized by impaired swallowing due to muscle weakness and heightened pharyngeal and upper esophageal constriction (Tack and Vantrappen 1997; Ortega, Martín, and Clavé 2017; Clavé and Shaker 2015; Muhle et al. 2015), affects the elderly with a prevalence ranging from 13.8 to 70%…”

“For instance, studies have reported no age-related changes in the duodenum (>70 years) (Lipski et al. 1992) and in the jejunum (65–82 years) (Corazza et al. 1986), whereas other studies reported age related changes in both parts of the small intestine.”

“Finally, a lack of consensus regarding the definition of protein digestion, and the different techniques used among studies (Trommelen, Tomé, and van Loon 2021), leave room for future research.”

“…et al. 2010; viljakainen et al. 2016) increase range in chewing strokes (Feldman et al. 1980; Hatch et al. 2001; Kohyama, Mioche, and Martin 2002; Bessadet et al. 2013; Mishellany-dutour et al. 2008; Peyron et al. 2004; wayler and Chauncey 1983; aguayo-Mendoza et al. 2020; (Grande et al. 1999;…”

“Current knowledge on the aging digestive system has been reviewed in order to adjust the in vitro models accordingly (Shani-Levi et al. 2017; Lee et al. 2023; Mackie, Mulet-Cabero, and Torcello-Gómez 2020).”

“Small bowel bacterial overgrowth increases with aging (18–80 years) along with concomitant diseases (Mitsui et al. 2006; Leite et al. 2022; Lewis et al. 1999; Parlesak et al. 2003).”

“The majority of studies showed that gastric emptying is delayed (Giezenaar et al. 2017; Moore et al. 1983; O’Donovan et al. 2005; Rayner et al. 2000; Shimamoto et al. 2002) with between 11 and 69% prolongation of emptying time in older adults (mean range 65–76 years old) compared to younger adults…”

“Nevertheless, some studies did not find an effect of aging on gastric emptying time (Hellmig et al. 2006; Madsen and Graff 2004; Madsen 1992) or only an age effect on gastric emptying for liquid foods (Kao et al. 1994) or lipid-rich foods (Nakae et al. 1999).”

“…al. 1993; Feldman et al. 1996 range prolonged emptying time (Brogna et al. 1999; Clarkston et al. 1997; di Francesco et al. 2005; evans et al. 1981; Kao et al. 1994; nakae et al. 1999; Pham et al. 2020; wegener et al. 1988 (Fikry 1968; laugier et al. 1991; vellas et al. 1988) no change enzyme…”

“Proton pump inhibitors, drugs that are often prescribed to older adults, also increase gastric pH (Freedberg, Lebwohl, and Abrams 2014; Scarpignato et al. 2016; Rayner and Horowitz 2013).”

“Prevalence range xerostomia (Åstrøm et al. 2019; Bakker et al. 2020; Fernandes et al. 2021; Glazar et al. 2010; Hahnel et al. 2014; Hochberg et al. 1998; Johansson et al. 2012; nederfors et al. 1997; ohara et al. 2011; ramsay et al. 2015; saunders and Friedman 2007; schein et al. 1999; so et al.…”

“Normal esophageal motility deteriorates with aging (Grande et al. 1999; Shaker and Lang 1994; Robbins, Bridges, and Taylor 2006), caused by changed sphincter contractility and pressure (Cock and Omari 2018; Bardan et al. 2000; Besanko et al. 2014), and muscular and neuronal changes (Milosavljevic…”

“Ideally, in vivo protein digestion is determined by measuring dietary amino acid disappearance in the gastrointestinal tract, at the level of the terminal ileum (Moughan and Wolfe 2019).”

“For instance, studies have reported no age-related changes in the duodenum (>70 years) (Lipski et al. 1992) and in the jejunum (65–82 years) (Corazza et al. 1986), whereas other studies reported age related changes in both parts of the small intestine.”

“This motility, together with the time in the intestine, are important for digestive enzymes to be able to access nutrients and exert their function (Lentle and Janssen 2008; Lentle and de Loubens 2015).”

“This hormone inhibits gastric emptying (Guilloteau et al. 2006), which corresponds to findings of delayed gastric emptying with age.”

“Newer and less invasive techniques to measure protein digestibility, like the dual tracer approach, will hopefully provide valuable data that will help direct the dietary advice for older adults in the near future (Engelen et al. 2014).”

“…and Lang 1994; Robbins, Bridges, and Taylor 2006), caused by changed sphincter contractility and pressure (Cock and Omari 2018; Bardan et al. 2000; Besanko et al. 2014), and muscular and neuronal changes (Milosavljevic et al. 2013; Meciano Filho, Carvalho, and de Souza 1995; Iida et al. 2013).”

“…1999; Clarkston et al. 1997; di Francesco et al. 2005; evans et al. 1981; Kao et al. 1994; nakae et al. 1999; Pham et al. 2020; wegener et al. 1988 (Fikry 1968; laugier et al. 1991; vellas et al. 1988) no change enzyme output or pancreatic function 3 204 55 = (Gullo et al. 1986; Gullo et al. 1983;…”

“In contrast, some studies did not report a difference in pancreatic function with age as measured with fecal elastase-1 (Gullo et al. 2009) or stimulation of pancreatic fluid by secretin (Gullo et al. 1983) and the fluorescein dilaurate test (Gullo et al. 1986).”

“Optimal protein intake provides adequate quantities of nitrogen and indispensable amino acids to meet requirements (Elango, Ball, and Pencharz 2012; Lee et al. 2016).”

“In fact, some studies have even shown an increased acidity with age (Cryer et al. 1992; Feldman and Cryer 1998; Russell et al. 1993).”

“In contrast, some studies did not report a difference in pancreatic function with age as measured with fecal elastase-1 (Gullo et al. 2009) or stimulation of pancreatic fluid by secretin (Gullo et al. 1983) and the fluorescein dilaurate test (Gullo et al. 1986).”

“This was observed during fasting (Anuras and Sutherland 1984; Fischer and Fadda 2016), and after consumption of a meal (Kagaya et al. 1997; Husebye and Engedal 1992) and has been commented on by others (Brogna et al. 1999; Clarkston et al. 1997; O’Mahony, O’Leary, and Quigley 2002).”

“…and Lang 1994; Robbins, Bridges, and Taylor 2006), caused by changed sphincter contractility and pressure (Cock and Omari 2018; Bardan et al. 2000; Besanko et al. 2014), and muscular and neuronal changes (Milosavljevic et al. 2013; Meciano Filho, Carvalho, and de Souza 1995; Iida et al. 2013).”

“…Peyron et al. 2004; wayler and Chauncey 1983; aguayo-Mendoza et al. 2020; (Grande et al. 1999; ren et al. 1995; Bardan et al. 2000; Kern et al. 1999; ren et al. 2000; shaker et al. 1993; Besanko et al (Grande et al. 1999; ren et al. 1995; Ferriolli et al. 1998; soergel, Zboralske, and Cryer et al.…”

“Pancreatic secretion and function change in humans with age (Chantarojanasiri et al. 2015), which has been shown by a 45% decrease in fluid flow rate, bicarbonate and enzyme secretion (Laugier et al. 1991; Fikry 1968; Vellas et al. 1988).”

“Concerning ileal protein digestibility, the growing rat and growing pig are widely used and are considered suitable models for healthy adults (Deglaire and Moughan 2012; FAO 2014; Hodgkinson et al. 2022).”

“…20–97 years (Smith et al. 2013) and is one of the potential causes of dry mouth (Hochberg et al. 1998; Glazar et al. 2010; Hahnel et al. 2014), which has increased prevalence with age (Johansson et al. 2012; Schein et al. 1999; Bakker et al. 2020; Fernandes et al. 2021; Viljakainen et al. 2016).”

“The number of teeth decreases with age (Müller, Naharro, and Carlsson 2007; Ozturk et al. 2013; Morales-Suárez-Varela et al. 2011) and the prevalence of being edentulous, i.e. lacking all teeth, ranges between 4 and 56% across studies (Table 2(a)) with age ranges of 65–92 years (Choufani et al.…”

“…et al. 1998; Johansson et al. 2012; nederfors et al. 1997; ohara et al. 2011; ramsay et al. 2015; saunders and Friedman 2007; schein et al. 1999; so et al. 2010; viljakainen et al. 2016) increase range in chewing strokes (Feldman et al. 1980; Hatch et al. 2001; Kohyama, Mioche, and Martin…”

“…with aging (Grande et al. 1999; Shaker and Lang 1994; Robbins, Bridges, and Taylor 2006), caused by changed sphincter contractility and pressure (Cock and Omari 2018; Bardan et al. 2000; Besanko et al. 2014), and muscular and neuronal changes (Milosavljevic et al. 2013; Meciano Filho, Carvalho,…”

“These reviews have varied in their specific focus, for example on malnutrition prevention (Rémond et al. 2015), drug absorption (Stillhart et al. 2020; Khan and Roberts 2018), diseases (Grassi et al. 2011) and motility (Gidwaney, Bajpai, and Chokhavatia 2016; O’Mahony, O’Leary, and Quigley 2002).”

“…et al. 1999; Shaker and Lang 1994; Robbins, Bridges, and Taylor 2006), caused by changed sphincter contractility and pressure (Cock and Omari 2018; Bardan et al. 2000; Besanko et al. 2014), and muscular and neuronal changes (Milosavljevic et al. 2013; Meciano Filho, Carvalho, and de Souza 1995;…”

“Another study observed that jejunal villi were wider in older adults aged over 60 years (Trbojević-Stanković et al. 2010)”

“Prevalence range xerostomia (Åstrøm et al. 2019; Bakker et al. 2020; Fernandes et al. 2021; Glazar et al. 2010; Hahnel et al. 2014; Hochberg et al. 1998; Johansson et al. 2012; nederfors et al. 1997; ohara et al. 2011; ramsay et al. 2015; saunders and Friedman 2007; schein et al. 1999; so et al.…”

“…1992; Feldman and Cryer 1998; Haruma et al. 2000; Hurwitz et al. 1997; iijima et al. 2004; nakamura, ogoshi, and Makuuchi 2006; Pilotto et al. 1994; shih et al. 2003; russell et al. 1993; Feldman et al. 1996 range prolonged emptying time (Brogna et al. 1999; Clarkston et al. 1997; di Francesco et…”

“…and Cryer et al. 1992; Feldman and Cryer 1998; Haruma et al. 2000; Hurwitz et al. 1997; iijima et al. 2004; nakamura, ogoshi, and Makuuchi 2006; Pilotto et al. 1994; shih et al. 2003; russell et al. 1993; Feldman et al. 1996 range prolonged emptying time (Brogna et al. 1999; Clarkston et al.…”

“Prevalence range xerostomia (Åstrøm et al. 2019; Bakker et al. 2020; Fernandes et al. 2021; Glazar et al. 2010; Hahnel et al. 2014; Hochberg et al. 1998; Johansson et al. 2012; nederfors et al. 1997; ohara et al. 2011; ramsay et al. 2015; saunders and Friedman 2007; schein et al. 1999; so et al.…”

“…Morales-Suárez-Varela et al. 2011) and the prevalence of being edentulous, i.e. lacking all teeth, ranges between 4 and 56% across studies (Table 2(a)) with age ranges of 65–92 years (Choufani et al. 2020; Ikebe et al. 2007; Saunders and Friedman 2007; Shariff et al. 2018; Ramsay et al. 2015).”

“Eating capability is determined by factors outside the mouth as a digestive organ as well, which is reviewed elsewhere (Sarkar 2019).”

“Some in vitro and in vivo animal studies have been undertaken to study absorption, which are extensively reviewed elsewhere (Milan and Cameron-Smith 2015).”

“This splanchnic extraction or first-pass metabolism represents the fraction of ingested amino acids taken up by organs of the digestive system during its first pass for their own metabolism (Jourdan et al. 2011).”

“…chewing duration increases (Kohyama, Mioche, and Martin 2002; Mioche, Bourdiol, and Peyron 2004; Mishellany-Dutour et al. 2008; Bessadet et al. 2013; Aguayo-Mendoza et al. 2020) to allow swallowing of the ingested food (Feldman et al. 1980; Peyron et al. 2004; Mioche, Bourdiol, and Peyron 2004;…”

“…considering 18 randomized controlled trials using this approach (Gorissen et al. 2020) included four studies investigating the effect of age with a total of 82 young and 83 older adults (Gorissen et al. 2014; Koopman et al. 2009; Pennings et al. 2011; Groen et al. 2016; Gorissen et al. 2020).”

“Prevalence range xerostomia (Åstrøm et al. 2019; Bakker et al. 2020; Fernandes et al. 2021; Glazar et al. 2010; Hahnel et al. 2014; Hochberg et al. 1998; Johansson et al. 2012; nederfors et al. 1997; ohara et al. 2011; ramsay et al. 2015; saunders and Friedman 2007; schein et al. 1999; so et al.…”

“Loss of cells correlates with higher slow wave velocity which is responsible for muscle contraction (Wang et al. 2021).”

“Until approximately 25 years of age, bite force increases with age, while afterwards, it decreases, resulting in lower muscle activity per chew for the elderly (Bakke et al. 1990; Newton et al. 1993; Nguyen et al. 2018; Palinkas et al. 2010).”

“…et al. 2020; Fernandes et al. 2021; Glazar et al. 2010; Hahnel et al. 2014; Hochberg et al. 1998; Johansson et al. 2012; nederfors et al. 1997; ohara et al. 2011; ramsay et al. 2015; saunders and Friedman 2007; schein et al. 1999; so et al. 2010; viljakainen et al. 2016) increase range in…”

“Immune function is deteriorating in older adults, T-cell proliferation is reduced (69–84 years) (Dillon et al. 2020) and IL-6 production is increased (67–77 years) (Man et al. 2015) with aging.”

“…prolonged emptying time (Brogna et al. 1999; Clarkston et al. 1997; di Francesco et al. 2005; evans et al. 1981; Kao et al. 1994; nakae et al. 1999; Pham et al. 2020; wegener et al. 1988 (Fikry 1968; laugier et al. 1991; vellas et al. 1988) no change enzyme output or pancreatic function 3 204 55 =…”

“The number of teeth decreases with age (Müller, Naharro, and Carlsson 2007; Ozturk et al. 2013; Morales-Suárez-Varela et al. 2011) and the prevalence of being edentulous, i.e. lacking all teeth, ranges between 4 and 56% across studies (Table 2(a)) with age ranges of 65–92 years (Choufani et al.…”

“Senior cats had lower nitrogen digestibility when consuming a diet high in fat and low in fiber (Schauf et al. 2021).”

“In contrast, some studies did not report a difference in pancreatic function with age as measured with fecal elastase-1 (Gullo et al. 2009) or stimulation of pancreatic fluid by secretin (Gullo et al. 1983) and the fluorescein dilaurate test (Gullo et al. 1986).”

“This was observed during fasting (Anuras and Sutherland 1984; Fischer and Fadda 2016), and after consumption of a meal (Kagaya et al. 1997; Husebye and Engedal 1992) and has been commented on by others (Brogna et al. 1999; Clarkston et al. 1997; O’Mahony, O’Leary, and Quigley 2002).”

“Similar concentrations were observed between young and older adults, but it appeared that the generic response was delayed by advancing age (van der Heijden et al. 2024).”

“Concerning structure, there is increased fibrosis in the pancreas (Saini et al. 2015; Löhr et al. 2018) and increased fat content (Yang et al. 2019; Moin et al. 2020).”

“However, the terminal ileum in humans can only be reached via an oral-or nasal-intestinal catheter (van Trijp et al. 2021) or by investigating ileostomy patients (FAO 2014), making ileal digestibility measurements challenging.”

“No difference in protein digestibility was found dependent on age and moisture content (Kim et al. 2021).”

“This can be partly explained by reduced chewing efficiency — determined by bite force, number of teeth, number of chewing cycles before swallowing, and the food particle size distribution — as well as reduced gastric acid secretion and slower gastric emptying [121].”

“Gastric chyme then undergoes further breakdown and hydrolysis in the intestine, with subsequent absorption of amino acids and peptides (Hinssen et al. 2024 ).”

“Host-derived polyamines maintain systemic and intracellular pools essential for basal cellular functions, including proliferation, differentiation, and tissue maintenance, while dietary polyamines absorbed primarily in the upper gastrointestinal tract, support circulating and tissue-associated…”

“This method takes the whole postprandial period into account, which is sensitive to differences in gastric emptying, which changes with aging [8].”

“[84,85] In parallel, aging is associated with marked shifts in gut microbiota composition, including reduced stability, increased inter-individual variability, and age-dependent microbial patterns that influence metabolic responses to food.”

“Standardized in vitro digestion models are widely used to evaluate changes in food components, including structural transformations, bio-accessibility, and digestibility, demonstrating their value as reliable tools for food and pharmaceutical analysis (Hinssen et al., 2024).”

“Older adults, for example, have reduced digestive capacity due to decreased enzyme and pepsin secretion, which affects protein digestion and absorption (Rémond et al. 2015; Hinssen et al. 2025).”

“With ageing, our digestive system becomes less efficient in absorbing certain nutrients e.g. vitamin B12, as a result of slower return of postprandial-raised gastric pH to acidic pH and bacterial overgrowth [44,45].”

“This result aligns with previous studies, which have suggested that changes in digestion, absorption, and appetite associated with aging may contribute to increased risk of malnutrition (59–61).”