The DOI matches its Crossref record; 32 of the 32 references it cites were found in a registry or an index; 14 of the 41 sources its claims cite were checked for support.
Rapamycin fed late in life extends lifespan in genetically heterogeneous mice
Open accessAbstract
Inhibition of the TOR signalling pathway by genetic or pharmacological intervention extends lifespan in invertebrates, including yeast, nematodes and fruitflies; however, whether inhibition of mTOR signalling can extend lifespan in a mammalian species was unknown. Here we report that rapamycin, an inhibitor of the mTOR pathway, extends median and maximal lifespan of both male and female mice when fed beginning at 600 days of age. On the basis of age at 90% mortality, rapamycin led to an increase of 14% for females and 9% for males. The effect was seen at three independent test sites in genetically heterogeneous mice, chosen to avoid genotype-specific effects on disease susceptibility. Disease patterns of rapamycin-treated mice did not differ from those of control mice. In a separate study, rapamycin fed to mice beginning at 270 days of age also increased survival in both males and females, based on an interim analysis conducted near the median survival point. Rapamycin may extend lifespan by postponing death from cancer, by retarding mechanisms of ageing, or both. To our knowledge, these are the first results to demonstrate a role for mTOR signalling in the regulation of mammalian lifespan, as well as pharmacological extension of lifespan in both genders. These findings have implications for further development of interventions targeting mTOR for the treatment and prevention of age-related diseases.
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Claims the paper makes
26 Own result · 9 Own interpretation · 6 No full text of the sources · 6 Own method · 5 Partly supported · 3 Supported so far · 2 Supported · 2 Not checked yet · accuracy not yet measured
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Inhibition of the TOR signalling pathway by genetic or pharmacological intervention extends lifespan in invertebrates, including yeast, nematodes and fruit flies1–5.”
§ Rapamycin fed late in life extends lifespan in genetically heterogeneous mice > Abstract
What the sources say
- Not checked — no full text of the sourcecites [1] Kaeberlein, M. et al. Regulation of yeast replicative life span by TOR and Sch9 in response to nutrients. Science 310, 1193–1196 (2005) source
- Supportedcites [2] Powers, R. W., Kaeberlein, M., Caldwell, S. D., Kennedy, B. K. & Fields, S. Extension of chronological life span in yeast by decreased TOR pathway signaling. Genes Dev. 20, 174–184 (2006) source
The Abstract reports that TOR-pathway mutations and pharmacological inhibition increase chronological lifespan in yeast. The Conclusion says evidence from yeast, worms and flies indicates a central role for TOR in lifespan extension when signalling is reduced. The paper supports the collective claim, though it does not establish both intervention types in each species. (LLM, conf=0.87)
- Not checked — no full text of the sourcecites [3] Jia, K., Chen, D. & Riddle, D. L. The TOR pathway interacts with the insulin signaling pathway to regulate C. elegans larval development, metabolism and life span. Development 131, 3897–3906 (2004) source
- Partly supportedcites [4] Kapahi, P. et al. Regulation of lifespan in Drosophila by modulation of genes in the TOR signaling pathway. Curr. Biol. 14, 885–890 (2004) sourceExperimental — accuracy not yet measured
The Abstract reports that genetic inhibition of TOR-pathway signalling extends lifespan in fruit flies, and the Introduction reports lifespan extension with TOR deficiency in nematodes. The paper does not report lifespan extension from TOR inhibition in yeast or from pharmacological inhibition; its mention of rapamycin describes a binding domain, not a drug intervention. (LLM, conf=0.88)
- Not checked — no full text of the sourcecites [5] Vellai, T. et al. Genetics: influence of TOR kinase on lifespan in C. elegans. Nature 426, 620 (2003) source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“To document biochemical effects of rapamycin at the dose used for the lifespan studies, we evaluated the phosphorylation status of ribosomal protein subunit S6 (rpS6), a target substrate of S6 kinase 1 in the mTOR signalling pathway20, in visceral white adipose tissue (a sensitive indicator of mTOR inhibition by rapamycin treatment in vivo).”
§ Rapamycin fed late in life extends lifespan in genetically heterogeneous mice > Abstract
What the sources say
- Partly supportedcites [20] Petroulakis, E., Mamane, Y., Le Bacquer, O., Shahbazian, D. & Sonenberg, N. mTOR signaling: implications for cancer and anticancer therapy. Br. J. Cancer 96 (Suppl.). R11–R15 (2007) sourceExperimental — accuracy not yet measured
The paper’s “Ribosomal protein S6 kinase” section places S6K1 downstream of mTOR, and its discussion of rapamycin says the drug inhibits mTOR. That supports the pathway rationale for measuring rpS6 phosphorylation, but the paper does not establish that it is a sensitive indicator of rapamycin-induced mTOR inhibition in vivo. (LLM, conf=0.83)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“At the cellular level, mTORC1 helps to coordinate growth and survival responses induced by alterations in nutrient availability, energy status, growth factor stimuli and exposure to potentially lethal cell stresses27–29; this strategic position at the nexus of nutrient/stress sensing pathways may contribute to the importance of TOR function in regulating lifespan in invertebrates and in mammals as”
§ Rapamycin fed late in life extends lifespan in genetically heterogeneous mice > Abstract
What the sources say
- Partly supportedcites [27] Wullschleger, S., Loewith, R. & Hall, M. N. TOR signaling in growth and metabolism. Cell 124, 471–484 (2006) sourceExperimental — accuracy not yet measured
Figure 2 (p. 5) and Stress (p. 7) describe mTORC1 as responding to nutrients, energy status, growth factors, and stress. “TOR Influences Memory and Aging in Adults” (p. 3) reports lifespan effects in yeast, worms, and flies, but explicitly says links between mTOR signaling and mammalian longevity had not yet been reported. The attribution is therefore supported for the sensing pathways and invertebrate lifespan, but not for an established role in mammalian lifespan. (LLM, conf=0.88)
- Not checked — no full text of the sourcecites [28] Reiling, J. H. & Sabatini, D. M. Stress and mTORture signaling. Oncogene 25, 6373–6383 (2006) source
- Partly supportedcites [29] Sonenberg, N. & Hinnebusch, A. G. New modes of translational control in development, behavior, and disease. Mol. Cell 28, 721–729 (2007) sourceExperimental — accuracy not yet measured
The paper’s discussion of metabolism (indexed as Abstract; no page supplied) describes the PI3K/Akt/mTOR pathway as coupling nutrient and mitogen availability to cellular and organismal metabolic state. It also reports extended lifespan in C. elegans after loss of an eIF4E isoform, but does not link TOR function itself to lifespan regulation in either invertebrates or mammals, or establish the proposed nutrient/stress-sensing explanation. (LLM, conf=0.85)
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Rapamycin may extend lifespan in old genetically heterogeneous mice through a combination of anti-neoplastic effects25,26 and effects on cellular stress resistance and response to nutrient dynamics27–29.”
§ Rapamycin fed late in life extends lifespan in genetically heterogeneous mice > Abstract
What the sources say
- Not checked — no full text of the sourcecites [25] Garber, K. Rapamycin’s resurrection: a new way to target the cancer cell cycle. J. Natl Cancer Inst. 93, 1517–1519 (2001) source
- Not matchedcites [26] Lorberg, A. & Hall, M. N. TOR: the first 10 years. Curr. Top. Microbiol. Immunol. 279, 1–18 (2004)
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Partly supportedcites [27] Wullschleger, S., Loewith, R. & Hall, M. N. TOR signaling in growth and metabolism. Cell 124, 471–484 (2006) sourceExperimental — accuracy not yet measured
The Stress section (p. 6) describes TOR signaling in cellular responses to hypoxia, low energy, and other stresses; the aging section (p. 3) links TOR inhibition to longer lifespan in yeast, worms, and flies, possibly through calorie restriction. But it explicitly says links between mTOR signaling and mammalian longevity had not yet been reported, so it does not support this proposed mechanism for lifespan extension in old mice. The anti-neoplastic clause carries separate citations. (LLM, conf=0.88)
- Not checked — no full text of the sourcecites [28] Reiling, J. H. & Sabatini, D. M. Stress and mTORture signaling. Oncogene 25, 6373–6383 (2006) source
- Partly supportedcites [29] Sonenberg, N. & Hinnebusch, A. G. New modes of translational control in development, behavior, and disease. Mol. Cell 28, 721–729 (2007) sourceExperimental — accuracy not yet measured
The supplied Abstract passages link mTOR signaling to nutrient availability and report that reduced translation protects against oxidative stress and extends lifespan in C. elegans. They do not establish that rapamycin extends lifespan in old genetically heterogeneous mice through those mechanisms. The anti-neoplastic effects are attached to different citations (25–26) in the citing sentence. (LLM, conf=0.84)
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: Rapamycin's effect on lifespan is mediated by inhibition of mTOR.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We report here that rapamycin, an inhibitor of the mTOR pathway, extends median and maximal lifespan of both male and female mice when fed beginning at 600 days of age.”
§ Rapamycin fed late in life extends lifespan in genetically heterogeneous mice > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: The genetically heterogeneous mouse population is representative enough that effects on lifespan are not genotype-specific.
- Rests on an assumption: Rapamycin's effect on lifespan is mediated by inhibition of mTOR.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Male mice at all three sites also had improved survival after rapamycin feeding (Figure 2).”
§ Rapamycin fed late in life extends lifespan in genetically heterogeneous mice > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Here we report that dietary encapsulated rapamycin increases mouse survival, including survival to the last decile, a measure of maximal lifespan.”
§ Rapamycin fed late in life extends lifespan in genetically heterogeneous mice > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Maximum lifespan was increased by rapamycin feeding.”
§ Rapamycin fed late in life extends lifespan in genetically heterogeneous mice > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Figure 3B shows that rapamycin reduced phosphorylated rpS6 4–5 fold when fed from 270 to about 800 days of age.”
§ Rapamycin fed late in life extends lifespan in genetically heterogeneous mice > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The effect was seen at three independent test sites in genetically heterogeneous mice, chosen to avoid genotype-specific effects on disease susceptibility.”
§ Rapamycin fed late in life extends lifespan in genetically heterogeneous mice > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: The genetically heterogeneous mouse population is representative enough that effects on lifespan are not genotype-specific.
- It may state two separate claims as one. 21
- Probably not a substantial claim. 14
Every source the paper cites for this claim was checked and supports it.
In the paper
“This coating increased the fraction of rapamycin that survived the food preparation process by 3- to 4-fold, and protected the agent from digestion in the stomach16.”
§ Rapamycin fed late in life extends lifespan in genetically heterogeneous mice > Methods Summary > Diet preparation
What the sources say
- Supportedcites [16] Nadon, N. L. et al. Design of aging intervention studies: the NIA interventions testing program. AGE 30, 187–199 (2008) source
In “Issues unique to long-term intervention studies,” the paper reports a threefold higher rapamycin concentration in chow made with encapsulated rather than unencapsulated rapamycin, consistent with the claimed 3- to 4-fold range. The same passage says the enteric coating protects rapamycin from the stomach’s acidic conditions. (LLM, conf=0.90)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Median lifespan estimates of control females were consistent across sites (881–895 days), and were similar to values noted in Cohort 2004, which ranged from 858 to 909 days15.”
§ Rapamycin fed late in life extends lifespan in genetically heterogeneous mice > Abstract
What the sources say
- Supportedcites [15] Miller, R. A. et al. An aging interventions testing program: study design and interim report. Aging Cell 6, 565–575 (2007) source
Table 1 (Discussion; page unavailable) gives female control medians of 858, 876, and 909 days across the three sites, matching the range attributed to the cited study. The Results report no significant difference in female control survival among sites. The 881–895-day range describes the citing document’s controls, not a result attributed to this source. (LLM, conf=0.91)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“At the cellular level, mTORC1 helps to coordinate growth and survival responses induced by alterations in nutrient availability, energy status, growth factor stimuli and exposure to potentially lethal cell stresses27–29; this strategic position at the nexus of nutrient/stress sensing pathways may contribute to the importance of TOR function in regulating lifespan in invertebrates and in mammals as”
§ Rapamycin fed late in life extends lifespan in genetically heterogeneous mice > Abstract
What the sources say
- Supportedcites [27] Wullschleger, S., Loewith, R. & Hall, M. N. TOR signaling in growth and metabolism. Cell 124, 471–484 (2006) source
Figure 2 (p. 5) states that mTORC1 responds to growth factors, cellular energy status, nutrients, and stress while controlling pathways that determine cell growth. The Stress section (p. 6) describes responses to hypoxia and DNA damage, and Macroautophagy (p. 8) describes TOR-regulated recycling that helps starved cells survive. Together, these support the broad claim about coordinating growth and survival responses. (LLM, conf=0.87)
- Not checked — no full text of the sourcecites [28] Reiling, J. H. & Sabatini, D. M. Stress and mTORture signaling. Oncogene 25, 6373–6383 (2006) source
- Not checked yetcites [29] Sonenberg, N. & Hinnebusch, A. G. New modes of translational control in development, behavior, and disease. Mol. Cell 28, 721–729 (2007) source
Checked before — its earlier verdict is held back until a new check runs.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
- Supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“The National Institute on Aging Interventions Testing Program (ITP) evaluates agents that may delay ageing and increase lifespan in genetically heterogeneous mice15–17.”
§ Rapamycin fed late in life extends lifespan in genetically heterogeneous mice > Abstract
What the sources say
- Not checked yetcites [15] Miller, R. A. et al. An aging interventions testing program: study design and interim report. Aging Cell 6, 565–575 (2007) source
Checked before — its earlier verdict is held back until a new check runs.
- Not checked yetcites [16] Nadon, N. L. et al. Design of aging intervention studies: the NIA interventions testing program. AGE 30, 187–199 (2008) source
Checked before — its earlier verdict is held back until a new check runs.
- Supportedcites [17] Strong, R. et al. Nordihydroguaiaretic acid and aspirin increase lifespan of genetically heterogeneous male mice. Aging Cell 7, 641–650 (2008) source
The Introduction says the NIA developed the ITP to evaluate agents considered plausible candidates for delaying aging in laboratory mice. It also states that the protocol uses genetically heterogeneous mice and tests for effects on lifespan. (LLM, conf=0.92)
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Not checked yet
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Because incidences of most diseases rise rapidly with age6, interventions that delay ageing would greatly benefit health7–8.”
§ Rapamycin fed late in life extends lifespan in genetically heterogeneous mice > Abstract
What the sources say
- Supportedcites [7] Miller, R. A. Extending life: scientific prospects and political obstacles. Milbank Q. 80, 155–174 (2002) source
In “Anti-geric Intervention: Slowing Aging in Laboratory Animals,” the paper says interventions that slow aging would delay late-life suffering and lengthen healthy adult life. It also argues that aging research could improve public health substantially more than research targeting one disease at a time. The claim reflects these projected benefits, not a demonstrated benefit in humans. (LLM, conf=0.93)
- Not matchedcites [8] Olshansky, S. J., Perry, D., Miller, R. A. & Butler, R. N. In pursuit of the longevity dividend. Scientist 20, 28–35 (2006)
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence. The paper’s conclusions may not depend on it.
- Supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“Initial evidence that reduced TOR function can extend longevity came primarily from studies in yeast1,2 and invertebrates3–5.”
§ Rapamycin fed late in life extends lifespan in genetically heterogeneous mice > Abstract
What the sources say
- Not checked — no full text of the sourcecites [1] Kaeberlein, M. et al. Regulation of yeast replicative life span by TOR and Sch9 in response to nutrients. Science 310, 1193–1196 (2005) source
- Supportedcites [2] Powers, R. W., Kaeberlein, M., Caldwell, S. D., Kennedy, B. K. & Fields, S. Extension of chronological life span in yeast by decreased TOR pathway signaling. Genes Dev. 20, 174–184 (2006) source
The Abstract reports that decreased TOR signaling increases chronological life span in yeast. The Conclusion places this finding alongside evidence from worms and flies, supporting the sentence’s description of early evidence from yeast and invertebrates. Page numbers are not available in our copy. (LLM, conf=0.93)
- Not checked — no full text of the sourcecites [3] Jia, K., Chen, D. & Riddle, D. L. The TOR pathway interacts with the insulin signaling pathway to regulate C. elegans larval development, metabolism and life span. Development 131, 3897–3906 (2004) source
- Supportedcites [4] Kapahi, P. et al. Regulation of lifespan in Drosophila by modulation of genes in the TOR signaling pathway. Curr. Biol. 14, 885–890 (2004) source
The Abstract reports that inhibiting TOR signaling extends lifespan in Drosophila, an invertebrate. This paper supports the invertebrate portion of the citing sentence; the yeast portion is attributed to other citations. (LLM, conf=0.93)
- Not checked — no full text of the sourcecites [5] Vellai, T. et al. Genetics: influence of TOR kinase on lifespan in C. elegans. Nature 426, 620 (2003) source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“When each site was evaluated separately, the beneficial effect of rapamycin for females was significant at each site (p < 0.005); for males, the effect was significant (p < 0.025) at UM and UT, but not at TJL.”
§ Rapamycin fed late in life extends lifespan in genetically heterogeneous mice > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Based on age at 90% mortality, rapamycin led to an increase of 14% for females and 9% for males.”
§ Rapamycin fed late in life extends lifespan in genetically heterogeneous mice > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Rapamycin-fed and control mice were then compared separately for each combination of site and gender. Rapamycin had a consistent benefit, compared to controls, with p-values ranging from 0.03 to 0.0001 (Figure 2).”
§ Rapamycin fed late in life extends lifespan in genetically heterogeneous mice > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Mean lifespan increases for females were 15%, 16%, and 7% (TJL, UM, UT), and life expectancy at 600 days increased by 45%, 48%, and 22% for females at the three sites.”
§ Rapamycin fed late in life extends lifespan in genetically heterogeneous mice > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The site-specific calculations documented a significant effect on females at both TJL (p = 0.0006) and UM (p = 0.0001); for males we noted a significant effect at both TJL (p = 0.008) and UT (p = 0.0001), with a marginal effect at UM (p = 0.07).”
§ Rapamycin fed late in life extends lifespan in genetically heterogeneous mice > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Summing across the three sites, 4.8% of the female control mice were alive at these ages, compared to 21.5% of the rapamycin-treated females (p < 0.0001). For males, the corresponding values were 5.9% of controls and 20.2% of rapamycin mice (p < 0.0001).”
§ Rapamycin fed late in life extends lifespan in genetically heterogeneous mice > Abstract
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Mean lifespan increases for males were 5%, 8%, and 15% (TJL, UM, UT), and male life expectancy at 600 days increased by 16%, 23% and 52%.”
§ Rapamycin fed late in life extends lifespan in genetically heterogeneous mice > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Blood levels of rapamycin in the treated mice were equivalent in males and females, between 60 and 70 ng/ml.”
§ Rapamycin fed late in life extends lifespan in genetically heterogeneous mice > Abstract
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“At the time of analysis, 51% of the females and 68% of the males had died, and a stratified log-rank test showed significantly lower mortality risk in the rapamycin-treated mice compared to controls, pooling across the three test sites (p = 0.0002 for males and p < 0.0001 for females).”
§ Rapamycin fed late in life extends lifespan in genetically heterogeneous mice > Abstract
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Mice treated with other agents (enalapril and CAPE) evaluated in parallel did not differ from controls at the doses used (Supplemental Figure 1).”
§ Rapamycin fed late in life extends lifespan in genetically heterogeneous mice > Abstract
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Although rapamycin postpones death, it did not change the distribution of presumptive causes of death.”
§ Rapamycin fed late in life extends lifespan in genetically heterogeneous mice > Abstract
plainn = 40- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“For data pooled across sites, a log-rank test rejected the null hypothesis that treatment and control groups did not differ (p < 0.0001); mice fed rapamycin were longer lived than controls (p < 0.0001) in both males and females.”
§ Rapamycin fed late in life extends lifespan in genetically heterogeneous mice > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These findings have implications for further development of interventions targeting mTOR for the treatment and prevention of age-related diseases.”
§ Rapamycin fed late in life extends lifespan in genetically heterogeneous mice > Abstract
plain- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence.
In the paper
“Because incidences of most diseases rise rapidly with age6, interventions that delay ageing would greatly benefit health7–8.”
§ Rapamycin fed late in life extends lifespan in genetically heterogeneous mice > Abstract
What the sources say
- Not checked yetcites [6] Kohn, R. R. Principles of Mammalian Aging 2nd edn 151 (Prentice-Hall, 1978)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Sufficient mice are used to provide 80% power to detect a 10% increase (or decrease) in mean lifespan with respect to unmanipulated controls of the same sex, even if data from one of the three test sites were to be unavailable.”
§ Rapamycin fed late in life extends lifespan in genetically heterogeneous mice > Abstract
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Beneficial effects of diet restriction (DR)21 and dwarf mutations, both of which extend lifespan in rodents, may to some degree result from repression of the mTOR complex 1 (mTORC1) pathway22,23.”
§ Rapamycin fed late in life extends lifespan in genetically heterogeneous mice > Abstract
What the sources say
- Not checked — no full text of the sourcecites [21] Masoro, E. J. Overview of caloric restriction and ageing. Mech. Ageing Dev. 126, 913–922 (2005) source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
In the paper
“The increase in both median and maximum lifespan seen in rapamycin-fed mice is consistent with the hypothesis that inhibiting the mTORC1 pathway retards mammalian ageing, but is not compelling proof that ageing rates are altered, which would require testing whether the intervention decelerates age-dependent changes in multiple organs, cell types, and intra-cellular and extra-cellular processes14.”
§ Rapamycin fed late in life extends lifespan in genetically heterogeneous mice > Abstract
What the sources say
- Not checked — no full text of the sourcecites [14] Flurkey, K., Currer, J. M. & Harrison, D. E. in The Mouse in Biomedical Research 2nd edn, Vol. III (eds Fox, J. G. et al.) 637–672 (Academic, 2007) source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: Rapamycin's effect on lifespan is mediated by inhibition of mTOR.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Our data justify special attention to the role of the TOR pathway in control of ageing in mammals and in the pathogenesis of late-life illnesses.”
§ Rapamycin fed late in life extends lifespan in genetically heterogeneous mice > Abstract
plain- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Importantly, the significant benefits of rapamycin on male (and female) survival at TJL could not have been affected by diet prior to drug administration, because at TJL both control and rapamycin-fed mice received the same chow (Purina 5LG6) throughout this period.”
§ Rapamycin fed late in life extends lifespan in genetically heterogeneous mice > Abstract
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These are the first results to demonstrate a role for mTOR signalling in the regulation of mammalian lifespan, as well as pharmacological extension of lifespan in both genders.”
§ Rapamycin fed late in life extends lifespan in genetically heterogeneous mice > Abstract
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: Rapamycin's effect on lifespan is mediated by inhibition of mTOR.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Rapamycin may extend lifespan by postponing death from cancer, by retarding mechanisms of ageing, or both.”
§ Rapamycin fed late in life extends lifespan in genetically heterogeneous mice > Abstract
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds. It may state two separate claims as one.
- Rests on an assumption: Rapamycin's effect on lifespan is mediated by inhibition of mTOR.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Control mice at UT and UM differed from those fed rapamycin, not only in exposure to rapamycin from 600 days of age, but also in specific formulation of the mouse chows (all based on the NIH-31 standard) used between weaning and 600 days.”
§ Rapamycin fed late in life extends lifespan in genetically heterogeneous mice > Abstract
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Rapamycin appears to reduce mid-life mortality risk when started at 270 days of age, but additional data are needed to provide an accurate estimate of effect size, and to evaluate effects on maximal longevity.”
§ Rapamycin fed late in life extends lifespan in genetically heterogeneous mice > Abstract
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Studies are simultaneously replicated at three test sites: The Jackson Laboratory (TJL), the University of Michigan (UM), and the University of Texas Health Science Center (UT).”
§ Rapamycin fed late in life extends lifespan in genetically heterogeneous mice > Abstract
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Interpretation is somewhat complicated by differences among sites in survival of control males, and because mice assigned to the rapamycin-fed group at UT and perhaps at UM had lower mortality prior to 600 days than controls.”
§ Rapamycin fed late in life extends lifespan in genetically heterogeneous mice > Abstract
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“An effective anti-ageing intervention that could be initiated later than the midpoint of the lifespan could prove to be especially relevant to clinical situations, in which the efficacy of anti-ageing interventions would be particularly difficult to test in younger volunteers.”
§ Rapamycin fed late in life extends lifespan in genetically heterogeneous mice > Abstract
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence.
The paper relies on this without support.
Whether inhibition of mTOR signalling can extend life in a mammalian species was unknown.
“However, whether inhibition of mTOR signalling can extend life in a mammalian species was unknown.”
The paper relies on this without support.
The genetically heterogeneous mouse population is representative enough that effects on lifespan are not genotype-specific.
“The effect was seen at three independent test sites in genetically heterogeneous mice, chosen to avoid genotype-specific effects on disease susceptibility.”
The paper relies on this without support.
Rapamycin's effect on lifespan is mediated by inhibition of mTOR.
“Rapamycin reduces function of the rapamycin target kinase TOR and has anti-neoplastic activities, and genetic inhibition of TOR extends lifespan in short-lived model organisms.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Rapamycin and its analogs (so-called ‘rapalogs’) suppress the SASP by inhibiting mTOR and appear to extend healthspan and lifespan in mice105,108,109.”
From Cellular senescence and senolytics: the path to the clinic (2022) · cites this paper as [108]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Additionally, rapamycin treatment increased lifespan and delayed certain ageing-related dysfunctions in mice234.”
From Cellular senescence in ageing: from mechanisms to therapeutic opportunities (2021) · cites this paper as [234]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“which might explain its beneficial impact on longevity [121,122].”
From The role of cellular senescence and SASP in tumour microenvironment (2023) · cites this paper as [122]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“marked increase in lifespan and enhance health-span in mice treated with rapamycin, a well-characterized inhibitor of mTOR (Harrison et al., 2009)”
From Protein Homeostasis and Aging: the importance of exquisite quality control (2011) · cites this paper as Harrison et al., 2009
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“In mice, treatment with rapamycin also extends longevity in what is considered the most robust chemical intervention to increase lifespan in mammals”
From The Hallmarks of Aging (2013) · cites this paper as Harrison et al., 2009
Experimental — accuracy not yet measured
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Interventions using chemical inducers of macroautophagy (another type of autophagy different from chaperone-mediated autophagy) have spurred extraordinary interest after the discovery that constant or intermittent administration of the mTOR inhibitor rapamycin can increase the lifespan of middle-aged mice (Blagosklonny, 2011; Harrison et al., 2009).”
From The Hallmarks of Aging (2013) · cites this paper as Harrison et al., 2009
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“When rapamycin is administered late in life, it extends lifespan (Harrison et al., 2009; Miller et al., 2011), slows aging in a dose-dependent manner, shows differential effects by sex (Wilkinson et al., 2012), and is synergistic with metformin.”
From Metformin as a tool to target aging (2016) · cites this paper as Harrison et al., 2009
The cited source says what the claim attributes to it.
In the citing paper
“starting with a landmark study by the National Institute on Aging Interventions Testing Program (NIA ITP) published in 2009 which demonstrated that rapamycin extended the lifespan of genetically heterogeneous mice 33.”
From Targeting the biology of aging with mTOR inhibitors (2023) · cites this paper as [33]
The cited source says what the claim attributes to it.
In the citing paper
“Importantly, unlike caloric restriction, another well validated longevity intervention, which is less efficacious when begun later in life 34, rapamycin robustly extends lifespan when dosing was not initiated until late in life when the mice were 20 months of age (equivalent to about a 60 year old human) 33,35.”
From Targeting the biology of aging with mTOR inhibitors (2023) · cites this paper as [33]
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“a well-known inhibitor of mTOR, rapamycin, inhibits the production of SASP factors”
From The role of cellular senescence and SASP in tumour microenvironment (2023) · cites this paper as [122]
Experimental — accuracy not yet measuredIn the citing paper
“mTOR signaling has been demonstrated to be involved in regulating mammalian lifespan (Harrison et al., 2009).”
From Mechanisms of Cellular Senescence: Cell Cycle Arrest and Senescence Associated Secretory Phenotype (2021) · cites this paper as Harrison et al., 2009
In the citing paper
“In 2009, rapamycin, an inhibitor of the mammalian target of rapamycin (mTOR) pathway, was shown to significantly extend the lifespan of mammals.58”
From Antiageing strategy for neurodegenerative diseases: from mechanisms to clinical advances (2025) · cites this paper as [58]
In the citing paper
“AMPK activators and the mTOR signalling pathway inhibitor rapamycin have considerable ramifications for longevity and managing age-related illnesses.58,402–404”
From Antiageing strategy for neurodegenerative diseases: from mechanisms to clinical advances (2025) · cites this paper as [58]
In the citing paper
“Animal models exploring the effect of rapamycin and rapalogs on longevity have determined their ability to extend lifespan167-169.”
From SARS-CoV-2, COVID-19 and the aging immune system (2021) · cites this paper as [169]
In the citing paper
“Moreover, it was recently shown that the TOR inhibitor rapamycin extends lifespan in mice even when treatment is initiated late in life (58).”
From Neural mechanisms of ageing and cognitive decline (2010) · cites this paper as [58]
In the citing paper
“Much of the literature suggests that the genetic regulation of mTOR signal transduction can slow the aging of many organisms [183–185].”
From Immunosenescence: a key player in cancer development (2020) · cites this paper as [184]
In the citing paper
“For instance, inhibition of the mTOR pathway (using the drug rapamycin), which has been shown to extend lifespan in a variety of model organisms (de Magalhaes et al., 2012;Harrison et al., 2009), is an effective SASP suppressor (Correia-Melo et al., 2016;Herranz et al., 2015;Laberge et al., 2015).”
From Stress, cell senescence and organismal ageing (2018) · cites this paper as Harrison et al., 2009
In the citing paper
“Depletion of ribosome subunits or interference with the target of rapamycin/ribosomal protein S6 kinase pathway, which functions to activate protein translation, were found to alter the lifespan of a variety of species including mammals (54–56).”
From Controlled DNA double-strand break induction in mice reveals post-damage transcriptome stability (2016) · cites this paper as [54]
In the citing paper
“Additionally, rapamycin has earned great interest over the years to prolong lifespan (195, 280), even when administered to aged animals (281).”
From Metabolic Flexibility as an Adaptation to Energy Resources and Requirements in Health and Disease (2018) · cites this paper as [281]
In the citing paper
“Middle-aged mice on a diet supplemented with rapamycin survived significantly longer (Harrison et al., 2009); however, reports of the potent immunosuppressive properties of rapamycin suggest that the drug is unsuitable for lifespan extension in humans.”
From The Search for Antiaging Interventions: From Elixirs to Fasting Regimens (2014) · cites this paper as Harrison et al., 2009
In the citing paper
“Rapamycin selectively activates autophagy through inhibiting the mTOR pathway [60] and can extend the lifespan of mice [79].”
From Iron accumulation in senescent cells is coupled with impaired ferritinophagy and inhibition of ferroptosis (2018) · cites this paper as [79]
Citations
Cites
Bradford, M. M. (1976) · Analytical Biochemistry · doi:10.1016/0003-2697(76)90527-3 · Cited by 255,302
TOR signaling in growth and metabolism
Wullschleger, S., Loewith, R., & Hall, M. N. (2006) · Cell · doi:10.1016/j.cell.2006.01.016 · Cited by 5,787
Regulation of lifespan in Drosophila by modulation of genes in the TOR signaling pathway
Kapahi, P., Zid, B. M., Harper, T., Koslover, D., Sapin, V., & Benzer, S. (2004) · Current Biology · doi:10.1016/j.cub.2004.03.059 · Cited by 1,293 · cited 1×
“showed more than one of the following clinical signs: (1) inability to eat or to drink; (2) severe lethargy, as indicated by a lack of response such as a reluctance to move when gently prodded with a forceps; (3) severe balance or gait disturbance; (4) rapid weight loss over a period of 1 week or more; or (5) a severe…”
BackgroundRegulation of Yeast Replicative Life Span by TOR and Sch9 in Response to Nutrients
Kaeberlein, M., Powers, R. W., Steffen, K. K., Westman, E. A., Hu, D., Dang, N., Kerr, E. O., Kirkland, K. T., Fields, S., & Kennedy, B. K. (2005) · Science · doi:10.1126/science.1115535 · Cited by 1,293 · cited 3×
“showed more than one of the following clinical signs: (1) inability to eat or to drink; (2) severe lethargy, as indicated by a lack of response such as a reluctance to move when gently prodded with a forceps; (3) severe balance or gait disturbance; (4) rapid weight loss over a period of 1 week or more; or (5) a severe…”
BackgroundInfluence of TOR kinase on lifespan in C. elegans
Vellai, T., Takacs-Vellai, K., Zhang, Y., Kovacs, A. L., Orosz, L., & Müller, F. (2003) · Nature · doi:10.1038/426620a · Cited by 1,057
The Mouse in Biomedical Research
(1983) · Elsevier eBooks · doi:10.1016/c2013-0-10677-0 · Cited by 1,021
Extension of Chronological Life Span in Yeast by Decreased TOR Pathway Signaling
Powers, R. W., Kaeberlein, M., Caldwell, S. D., Kennedy, B. K., & Fields, S. (2006) · Genes & Development · doi:10.1101/gad.1381406 · Cited by 982 · cited 1×
“showed more than one of the following clinical signs: (1) inability to eat or to drink; (2) severe lethargy, as indicated by a lack of response such as a reluctance to move when gently prodded with a forceps; (3) severe balance or gait disturbance; (4) rapid weight loss over a period of 1 week or more; or (5) a severe…”
BackgroundOverview of caloric restriction and ageing
Masoro, E. J. (2005) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2005.03.012 · Cited by 879
Mouse Models in Aging Research
FLURKEY, K., MCURRER, J., & HARRISON, D. (2007) · The Mouse in Biomedical Research · doi:10.1016/b978-012369454-6/50074-1 · Cited by 723
Self-citationJia, K., Chen, D., & Riddle, D. L. (2004) · Development · doi:10.1242/dev.01255 · Cited by 615
Research works printed but not linked: 1
- Schneider, E. L. & Miller, R. A. in Brockelhurst's Textbook of Geriatric Medicine (eds Tallis, R., Fillit, H. & Brockelhurst, J. C.) 193–199 (Churchill Livingstone, 1998)
Cited by
Sorted by citations
Items 801–900 of 3,881
Deng, H., & Mi, M. (2016) · Neurochemical Research · doi:10.1007/s11064-016-1950-9 · Cited by 96
Latorre, E., Birar, V. C., Sheerin, A. N. P., Jeynes, J. C. C., Hooper, A., Dawe, H. R., Melzer, D. R., Cox, L. S., Faragher, R., Ostler, E. L., et al. (2017) · BMC Cell Biology · doi:10.1186/s12860-017-0147-7 · Cited by 96
Interventions to promote cardiometabolic health and slow cardiovascular ageing
Fontana, L. (2018) · Nature Reviews Cardiology · doi:10.1038/s41569-018-0026-8 · Cited by 96
Current nutritional and pharmacological anti-aging interventions
Ros, M., & Carrascosa, J. M. (2020) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2019.165612 · Cited by 86
Resveratrol and rapamycin: are they anti‐aging drugs?
Kaeberlein, M. R. (2010) · BioEssays · doi:10.1002/bies.200900171 · Cited by 96
Macip, C. C., Hasan, R., Hoznek, V., Kim, J., Metzger, L. E., Sethna, S., & Davidsohn, N. (2023) · doi:10.1101/2023.01.04.522507 · Cited by 95
Mammalian target of rapamycin signaling in diabetic cardiovascular disease
Chong, Z., & Maiese, K. (2012) · Cardiovascular Diabetology · doi:10.1186/1475-2840-11-45 · Cited by 95
Macip, C. C., Hasan, R., Hoznek, V., Kim, J., Lu, Y. R., Metzger, L. E., Sethna, S., & Davidsohn, N. (2024) · Cellular Reprogramming · doi:10.1089/cell.2023.0072 · Cited by 95
Insulin Resistance and Aging: A Cause or a Protective Response?
Barzilai, N., & Ferrucci, L. (2012) · The Journals of Gerontology Series A · doi:10.1093/gerona/gls145 · Cited by 95
Aberrant mTOR activation in senescence and aging: A mitochondrial stress response?
Nacarelli, T., Azar, A., & Sell, C. (2014) · Experimental Gerontology · doi:10.1016/j.exger.2014.11.004 · Cited by 95
Bae, Y., Son, Y., Kim, C., Kim, K. S., Hyun, S. H., Woo, H. G., Jee, B. A., Choi, J., Sung, H., Choi, H.-C., et al. (2018) · The Journals of Gerontology Series A · doi:10.1093/gerona/gly208 · Cited by 95
Lowered Insulin Signalling Ameliorates Age-Related Sleep Fragmentation in Drosophila
Metaxakis, A., Tain, L. S., Grönke, S., Hendrich, O., Hinze, Y., Birras, U., & Partridge, L. (2014) · PLoS Biology · doi:10.1371/journal.pbio.1001824 · Cited by 94
Mihaylova, M. M., Chaix, A., Delibegović, M., Ramsey, J. J., Bass, J. T., Melkani, G. C., Singh, R., Chen, Z., Ja, W. W., Shirasu-Hiza, M., et al. (2023) · Cell Metabolism · doi:10.1016/j.cmet.2023.06.008 · Cited by 97
Smith, E. D., Prieto, G. A., Tong, L., Sears‐Kraxberger, I., Rice, J. D., Steward, O., & Cotman, C. W. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.568659 · Cited by 94
Neuronal Responses to Physiological Stress
Kagias, K., Nehammer, C., & Pocock, R. (2012) · Frontiers in Genetics · doi:10.3389/fgene.2012.00222 · Cited by 94
mTOR signaling networks: mechanistic insights and translational frontiers in disease therapeutics
Zhang, H., Xiao, X., Pan, Z., & Dokudovskaya, S. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02493-4 · Cited by 94
Zhavoronkov, A. A. (2020) · Aging · doi:10.18632/aging.102988 · Cited by 93
Busada, J. T., Niedenberger, B. A., Velte, E. K., Keiper, B. D., & Geyer, C. B. (2015) · Developmental Biology · doi:10.1016/j.ydbio.2015.08.004 · Cited by 93
Epigenetic Mechanisms Impacting Aging: A Focus on Histone Levels and Telomeres
Song, S., & Johnson, F. B. (2018) · Genes · doi:10.3390/genes9040201 · Cited by 95
Histone Modifications as an Intersection Between Diet and Longevity
Molina‐Serrano, D., Kyriakou, D., & Kirmizis, A. (2019) · Frontiers in Genetics · doi:10.3389/fgene.2019.00192 · Cited by 94
Dose-dependent effects of mTOR inhibition on weight and mitochondrial disease in mice
Johnson, S. C., Yanos, M. E., Bitto, A., Castanza, A. S., Gagnidze, A., González, B., Gupta, K., Hui, J., Jarvie, C., Johnson, B. M., et al. (2015) · Frontiers in Genetics · doi:10.3389/fgene.2015.00247 · Cited by 93
Yang, J., Zhou, X., Fan, X., Xiao, M., Yang, D., Liang, B., Dai, M., Shan, L., Lu, J., Lin, Z., et al. (2016) · Blood · doi:10.1182/blood-2015-10-672964 · Cited by 93
Redmann, M., Darley-Usmar, V. M., & Zhang, J. (2016) · Aging and Disease · doi:10.14336/ad.2015.0820 · Cited by 93
Beclin 1 Complex in Autophagy and Alzheimer Disease
Jaeger, P. A., & Wyss‐Coray, T. (2010) · Archives of Neurology · doi:10.1001/archneurol.2010.258 · Cited by 93
Age‐related anabolic resistance after endurance‐type exercise in healthy humans
Durham, W. J., Casperson, S. L., Dillon, E. L., Keske, M. A., Paddon‐Jones, D., Sanford, A. P., Hickner, R. C., Grady, J. J., & Sheffield‐Moore, M. (2010) · The FASEB Journal · doi:10.1096/fj.09-150177 · Cited by 93
The Role of Rapamycin in Healthspan Extension via the Delay of Organ Aging
Zhang, Y., Zhang, J., & Wang, S. (2021) · Ageing Research Reviews · doi:10.1016/j.arr.2021.101376 · Cited by 92
Dehghan, E., Zhang, Y., Saremi, B., Yadavali, S., Hakimi, A., Dehghani, M., Goodarzi, M., Tu, X., Robertson, S., Lin, R., et al. (2017) · Nature Communications · doi:10.1038/s41467-017-02394-3 · Cited by 92
Low-dose rapamycin extends lifespan in a mouse model of mtDNA depletion syndrome
Siegmund, S. E., Yang, H., Sharma, R., Javors, M., Skinner, O., Mootha, V., Hirano, M., & Schon, E. A. (2017) · Human Molecular Genetics · doi:10.1093/hmg/ddx341 · Cited by 92
Self-citationm TORC 2‐ SGK ‐1 acts in two environmentally responsive pathways with opposing effects on longevity
Mizunuma, M., Neumann‐Haefelin, E., Moroz, N., Li, Y., & Blackwell, T. K. (2014) · Aging Cell · doi:10.1111/acel.12248 · Cited by 92
Can blocking inflammation enhance immunity during aging?
Chambers, E. S., & Akbar, A. N. (2020) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2020.03.016 · Cited by 92
Extensive accumulation of misfolded protein aggregates during natural aging and senescence
Cuanalo-Contreras, K., Schulz, J., Mukherjee, A., Park, K.-W., Armijo, E., & Soto, C. (2023) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.1090109 · Cited by 92
Autophagy and the kidney: health and disease
Takabatake, Y., Kimura, T., Takahashi, A., & Isaka, Y. (2014) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gft535 · Cited by 92
Senescent Cells Contribute to the Physiological Remodeling of Aged Lungs
Calhoun, C., Shivshankar, P., Saker, M., Sloane, L. B., Livi, C. B., Sharp, Z. D., Orihuela, C. J., Adnot, S., White, E. S., Richardson, A., et al. (2016) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/glu241 · Cited by 92
Self-citationRapamycin, Autophagy, and Alzheimer's Disease.
Cai, Z., & Yan, L. (2013) · PubMed · Cited by 97
Hyper-mitogenic drive coexists with mitotic incompetence in senescent cells
Leontieva, O. V., Lenzo, F. L., Demidenko, Z. N., & Blagosklonny, M. V. (2012) · Cell Cycle · doi:10.4161/cc.22937 · Cited by 92
Tuberous sclerosis complex–mediated mTORC1 overactivation promotes age-related hearing loss
Fu, X., Sun, X., Zhang, L., Jin, Y., Chai, R., Yang, L., Zhang, A., Liu, X., Bai, X., Li, J., et al. (2018) · Journal of Clinical Investigation · doi:10.1172/jci98058 · Cited by 92
Interventions for age-related diseases: Shifting the paradigm
Figueira, I., Fernandes, A. M. A., Mladenović, A., Lopez-Contreras, A. J., Henriques, C. M., Selman, C., Ferreiro, E. B., Gonos, E. S., Trejo, J. L., Misra, J., et al. (2016) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2016.09.009 · Cited by 92
Hasty, P., Sharp, Z. D., Curiel, T. J., & Campisi, J. (2012) · Cell Cycle · doi:10.4161/cc.22912 · Cited by 92
Self-citationA triple drug combination targeting components of the nutrient-sensing network maximizes longevity
Castillo-Quan, J. I., Tain, L. S., Kinghorn, K. J., Li, L., Grönke, S., Hinze, Y., Blackwell, T. K., Bjedov, I., & Partridge, L. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1913212116 · Cited by 91
Autophagy regulates chlorpyrifos-induced apoptosis in SH-SY5Y cells
Park, J. H., Lee, J. E., Shin, I. C., & Koh, H. C. (2013) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2013.01.013 · Cited by 91
Cholesterol homeostasis: a key to prevent or slow down neurodegeneration
Anchisi, L., Dessì, S., Pani, A., & Mandas, A. (2013) · Frontiers in Physiology · doi:10.3389/fphys.2012.00486 · Cited by 91
Ferrosenescence: The iron age of neurodegeneration?
Sfera, A., Bullock, K., Price, A. I., Inderias, L., & Osorio, C. P. (2017) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2017.11.012 · Cited by 91
Once again on rapamycin-induced insulin resistance and longevity: despite of or owing to
Blagosklonny, M. V. (2012) · Aging · doi:10.18632/aging.100461 · Cited by 91
mTORC1 Overactivation as a Key Aging Factor in the Progression to Type 2 Diabetes Mellitus
Guillén, C., & Benito, M. (2018) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00621 · Cited by 91
Mesenchymal stem cell aging: Mechanisms and influences on skeletal and non-skeletal tissues
Liu, H., Xia, X., & Li, B. (2015) · Experimental Biology and Medicine · doi:10.1177/1535370215591828 · Cited by 91
Aging and gastrointestinal neuromuscular function: insights from within and outside the gut
Bitar, K. N., Meerveld, B. G., Saad, R., & Wiley, J. W. (2011) · Neurogastroenterology & Motility · doi:10.1111/j.1365-2982.2011.01678.x · Cited by 91
Rapamycin activates autophagy in Hutchinson-Gilford progeria syndrome
Graziotto, J. J., Cao, K., Collins, F. S., & Krainc, D. (2012) · Autophagy · doi:10.4161/auto.8.1.18331 · Cited by 91
Benvéniste, O., Hogrel, J., Belin, L., Annoussamy, M., Bachasson, D., Rigolet, A., Laforêt, P., Dzangué-Tchoupou, G., Salem, J., Nguyen, L. S., et al. (2020) · The Lancet Rheumatology · doi:10.1016/s2665-9913(20)30280-0 · Cited by 91
The role of hydrogen sulfide in aging and age-related pathologies
Perridon, B. W., Leuvenink, H. G. D., Hillebrands, J., van Goor, H., & Bos, E. M. (2016) · Aging · doi:10.18632/aging.101026 · Cited by 90
Qin, Y., Liu, Y., Hao, W., Decker, Y., Tomic, I., Menger, M. D., Liu, C., & Fassbender, K. (2016) · The Journal of Immunology · doi:10.4049/jimmunol.1600873 · Cited by 90
Proteomics and metabolomics in ageing research: from biomarkers to systems biology
Hoffman, J. M., Lyu, Y., Pletcher, S. D., & Promislow, D. (2017) · Essays in Biochemistry · doi:10.1042/ebc20160083 · Cited by 90
Towards a unified mechanistic theory of aging
Barja, G. (2019) · Experimental Gerontology · doi:10.1016/j.exger.2019.05.016 · Cited by 90
The NLRP3 Inflammasome as a Critical Actor in the Inflammaging Process
Sebastian-Valverde, M., & Pasinetti, G. M. (2020) · Cells · doi:10.3390/cells9061552 · Cited by 90
mTORC1 signaling and regulation of pancreatic β-cell mass
Blandino-Rosano, M., Chen, A. Y., Scheys, J. O., Alejandro, E. U., Gould, A. P., Taranukha, T., Elghazi, L., CRAS-MÉNEUR, C. M. H., & Bernal‐Mizrachi, E. (2012) · Cell Cycle · doi:10.4161/cc.20036 · Cited by 90
Biosynthesis of rapamycin and its regulation: past achievements and recent progress
Park, S. R., Yoo, Y. J., Ban, Y. H., & Yoon, Y. J. (2010) · The Journal of Antibiotics · doi:10.1038/ja.2010.71 · Cited by 90
Regan, J. C., Lu, Y., Ureña, E., Meilenbrock, R. L., Catterson, J. H., Kißler, D., Fröhlich, J., Funk, E., & Partridge, L. (2022) · Nature Aging · doi:10.1038/s43587-022-00308-7 · Cited by 90
“Treatment of genetically heterogenous mice induced lifespan extension, to a greater extent in females than in males 25,26 .”
Ma, S., Upneja, A., Galecki, A., Tsai, Y.-M., Burant, C. F., Raskind, S., Zhang, Q., Zhang, Z. D., Seluanov, A., Gorbunova, V., et al. (2016) · eLife · doi:10.7554/elife.19130 · Cited by 89
Self-citationAutophagy and Tubular Cell Death in the Kidney
Havasi, A., & Dong, Z. (2016) · Seminars in Nephrology · doi:10.1016/j.semnephrol.2016.03.005 · Cited by 89
Sphingolipids and lifespan regulation
Huang, X., Withers, B. R., & Dickson, R. C. (2013) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2013.08.006 · Cited by 89
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Dominick, G., Berryman, D. E., List, E. O., Kopchick, J. J., Li, X., Miller, R. A., & Garcia, G. G. (2015) · Endocrinology · doi:10.1210/en.2014-1690 · Cited by 79
Self-citationHexosamine pathway and (ER) protein quality control
Denzel, M. S., & Antebi, A. (2014) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2014.10.001 · Cited by 89
Targeting the SASP to combat ageing: Mitochondria as possible intracellular allies?
Birch, J., & Passos, J. F. (2017) · BioEssays · doi:10.1002/bies.201600235 · Cited by 89
Brandhorst, S., Wei, M., Hwang, S., Morgan, T. E., & Longo, V. D. (2013) · Experimental Gerontology · doi:10.1016/j.exger.2013.02.016 · Cited by 89
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Blagosklonny, M. V. (2010) · Aging · doi:10.18632/aging.100149 · Cited by 89
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Welz, P.-S., & Benitah, S. A. (2019) · Journal of Molecular Biology · doi:10.1016/j.jmb.2019.12.036 · Cited by 90
mTOR-dependent translation amplifies microglia priming in aging mice
Keane, L., Antignano, I., Riechers, S., Zollinger, R., Dumas, A. A., Offermann, N., Bernis, M. E., Russ, J., Graelmann, F. J., McCormick, P. N., et al. (2020) · Journal of Clinical Investigation · doi:10.1172/jci132727 · Cited by 93
Cellular Senescence: Mechanisms and Therapeutic Potential
Liao, Z., Yeo, H. L., Wong, S. W., & Zhao, Y. X. (2021) · Biomedicines · doi:10.3390/biomedicines9121769 · Cited by 89
Nalbandian, A., Llewellyn, K. J., Nguyen, C. C., Yazdi, P. G., & Kimonis, V. E. (2015) · PLoS ONE · doi:10.1371/journal.pone.0122888 · Cited by 89
RetractedAging and brain rejuvenation as systemic events
Bouchard, J. J., & Villeda, S. (2014) · Journal of Neurochemistry · doi:10.1111/jnc.12969 · Cited by 90
Garza-Lombó, C., & Gonsebatt, M. E. (2016) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2016.00157 · Cited by 90
Acute mTOR inhibition induces insulin resistance and alters substrate utilization in vivo
Kleinert, M., Sylow, L., Fazakerley, D. J., Krycer, J. R., Thomas, K. C., Oxboll, A., Jordy, A. B., Jensen, T. E., Yang, G., Schjerling, P., et al. (2014) · Molecular Metabolism · doi:10.1016/j.molmet.2014.06.004 · Cited by 89
SH3BP4 Is a Negative Regulator of Amino Acid-Rag GTPase-mTORC1 Signaling
Kim, Y.-M., Stone, M., Hwang, T. H., Kim, Y.-G., Dunlevy, J. R., Griffin, T. J., & Kim, D.-H. (2012) · Molecular Cell · doi:10.1016/j.molcel.2012.04.007 · Cited by 88
Lysosomes: regulators of autophagy in the retinal pigmented epithelium
Sinha, D., Valapala, M., Shang, P., Hose, S., Grebe, R., Lutty, G. A., Zigler, J. S., Kaarniranta, K., & Handa, J. T. (2016) · Experimental Eye Research · doi:10.1016/j.exer.2015.08.018 · Cited by 88
Zanco, B., Mirth, C. K., Sgrò, C. M., & Piper, M. D. W. (2021) · eLife · doi:10.7554/elife.62335 · Cited by 88
The Regulation of Aging and Longevity: A New and Complex Role of p53
Feng, Z., Lin, M., & Wu, R. (2011) · Genes & Cancer · doi:10.1177/1947601911410223 · Cited by 88
Harnessing the mTOR Pathway for Tuberculosis Treatment
Singh, P., & Subbian, S. (2018) · Frontiers in Microbiology · doi:10.3389/fmicb.2018.00070 · Cited by 88
Impaired autophagy activity is linked to elevated ER-stress and inflammation in aging adipose tissue
Ghosh, A. K., Mau, T., O’Brien, M., Garg, S., & Yung, R. L. (2016) · Aging · doi:10.18632/aging.101083 · Cited by 88
Molecular damage in cancer: an argument for mTOR-driven aging
Blagosklonny, M. V. (2011) · Aging · doi:10.18632/aging.100422 · Cited by 88
Promoting Autophagic Clearance: Viable Therapeutic Targets in Alzheimer's Disease
Friedman, L. G., Qureshi, Y. H., & Yu, W. H. (2014) · Neurotherapeutics · doi:10.1007/s13311-014-0320-z · Cited by 89
Lublin, A. L., Isoda, F., Patel, H., Yen, K., Nguyen, L., Hajje, D., Schwartz, M., & Mobbs, C. V. (2011) · PLoS ONE · doi:10.1371/journal.pone.0027762 · Cited by 88
Host Resistance and Immune Aging
Bandaranayake, T., & Shaw, A. C. (2016) · Clinics in Geriatric Medicine · doi:10.1016/j.cger.2016.02.007 · Cited by 88
Drake, J. C., Peelor, F. F., Biela, L. M., Watkins, M. K., Miller, R. A., Hamilton, K. L., & Miller, B. F. (2013) · The Journals of Gerontology Series A · doi:10.1093/gerona/glt047 · Cited by 87
Self-citationHou, Y.-S., Guan, J.-J., Xu, H.-D., Wu, F., Sheng, R., & Qin, Z.-H. (2015) · Molecular and Cellular Biology · doi:10.1128/mcb.00285-15 · Cited by 87
Mitochondria and Organismal Longevity
Hwang, A. B., Jeong, D., & Lee, S. (2012) · Current Genomics · doi:10.2174/138920212803251427 · Cited by 87
Pharmacological Strategies to Retard Cardiovascular Aging
Alfaras, I., Germanio, C. D., Bernier, M., Csiszár, A., Ungvari, Z. I., Lakatta, E. G., & de Cabo, R. (2016) · Circulation Research · doi:10.1161/circresaha.116.307475 · Cited by 87
Lucid, C., Savani, B. N., Engelhardt, B. G., Shah, P. D., Clifton, C., Greenhut, S. L., Vaughan, L. A., Kassim, A. A., Schuening, F., & Jagasia, M. (2010) · Bone Marrow Transplantation · doi:10.1038/bmt.2010.152 · Cited by 87
Matsuzaki, T., Matsushita, T., Tabata, Y., Saito, T., Matsumoto, T., Nagai, K., Kuroda, R., & Kurosaka, M. (2014) · Biomaterials · doi:10.1016/j.biomaterials.2014.08.041 · Cited by 87
Modulation of telomere protection by the PI3K/AKT pathway
Méndez‐Pertuz, M., Martínez, P., Blanco‐Aparicio, C., Gómez‐Casero, E., García, A. B., Martinez-Torrecuadrada, J. L., Palafox, M., Cortés, J., Serra, V., Pastor, J., et al. (2017) · Nature Communications · doi:10.1038/s41467-017-01329-2 · Cited by 88
The role of autophagy in cancer: from molecular mechanism to therapeutic window
Jalali, P., Shahmoradi, A., Samii, A., Mazloomnejad, R., Hatamnejad, M. R., Saeed, A., Namdar, A., & Salehi, Z. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1528230 · Cited by 89
Autophagy and mTOR signaling during intervertebral disc aging and degeneration
Yurube, T., Ito, M., Kakiuchi, Y., Kuroda, R., & Kakutani, K. (2020) · JOR Spine · doi:10.1002/jsp2.1082 · Cited by 86
Rapamycin extends life span of Rb1+/− mice by inhibiting neuroendocrine tumors
Livi, C. B., Hardman, R. L., Christy, B. A., Dodds, S. G., Jones, D., Williams, C. E., Strong, R., Bokov, A. F., Javors, M. A., Ikeno, Y., et al. (2013) · Aging · doi:10.18632/aging.100533 · Cited by 86
Self-citationDivergent tissue and sex effects of rapamycin on the proteasome-chaperone network of old mice
Rodriguez, K. A., Dodds, S. G., Strong, R., Galván, V., Sharp, Z. D., & Buffenstein, R. (2014) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2014.00083 · Cited by 86
Self-citationRapamycin Is Neuroprotective in a Rat Chronic Hypertensive Glaucoma Model
Su, W., Li, Z., Jia, Y., & Zhuo, Y. (2014) · PLoS ONE · doi:10.1371/journal.pone.0099719 · Cited by 86
Targeting the Prodromal Stage of Alzheimer's Disease: Bioenergetic and Mitochondrial Opportunities
Caldwell, C. C., Yao, J., & Brinton, R. D. (2014) · Neurotherapeutics · doi:10.1007/s13311-014-0324-8 · Cited by 86
Suppression of replicative senescence by rapamycin in rodent embryonic cells
Pospelova, T. V., Leontieva, O. V., Bykova, T. V., Zubova, S. G., Pospelov, V. A., & Blagosklonny, M. V. (2012) · Cell Cycle · doi:10.4161/cc.20882 · Cited by 86
Edrey, Y. H., Casper, D., Huchon, D., Mele, J., Gelfond, J., Kristan, D. M., Nevo, E., & Buffenstein, R. (2011) · Aging Cell · doi:10.1111/j.1474-9726.2011.00772.x · Cited by 86
Börsch, A., Ham, D. J., Mittal, N., Tintignac, L. A., Migliavacca, E., Feige, J. N., Rüegg, M. A., & Zavolan, M. (2021) · Communications Biology · doi:10.1038/s42003-021-01723-z · Cited by 85
mTORC Inhibitors as Broad-Spectrum Therapeutics for Age-Related Diseases
Walters, H. E., & Cox, L. S. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19082325 · Cited by 85
Hepatic signaling by the mechanistic target of rapamycin complex 2 (mTORC2)
Lamming, D. W., Demirkan, G., Boylan, J. M., Mihaylova, M. M., Peng, T., Ferreira, J., Neretti, N., Salomon, A. R., Sabatini, D. M., & Gruppuso, P. A. (2013) · The FASEB Journal · doi:10.1096/fj.13-237743 · Cited by 85
Regulation of autophagy by mitochondrial phospholipids in health and diseases
Hsu, P., & Shi, Y. (2016) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2016.08.003 · Cited by 86
Metadata
- Authors
- Harrison, D. E., Strong, R., Sharp, Z. D., Nelson, J. F., Astle, C. M., Flurkey, K., Nadon, N. L., Wilkinson, J. E., Frenkel, K., Carter, C. S., Pahor, M., Javors, M. A., Fernandez, E., & Miller, R. A.
- Affiliations
- Jackson Laboratory (US)
- The University of Texas at San Antonio Health Science Center (US)
- National Institutes of Health (US)
- University of Michigan (US)
- NYU Langone Health (US)
- University of Florida (US)
- Corresponding author
- Harrison, David E.
- ORCID
- Venue
- Nature
- Published
- 2009-07
- Volume
- 460
- Issue
- 7253
- Pages
- 392-395
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC2786175
- OpenAlex
- W2048376025
- Cited by
- 3,766
- References
- 32
- Citations by year
- 2026: 185 · 2025: 208 · 2024: 182 · 2023: 199 · 2022: 211 · 2021: 225 · 2020: 194 · 2019: 252 · 2018: 202 · 2017: 219 · 2016: 232 · 2015: 249 · 2014: 254 · 2013: 228 · 2012: 262
- FWCI
- 74.45
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- The Mouseion at the JAXlibrary (Jackson Laboratory) (submittedVersion)
- Funders
- National Institute on Aging (AG 022308, AG13319, P30AG025707, AG022307, AG022303, AG025707, P30AG013319, U01AG022307, P30AG028740, U01AG022308, U01AG022303)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Keywords
- rapamycin, mTOR signaling, TOR signaling, lifespan extension, aging, genetically heterogeneous mice, sex differences in longevity, age-related diseases, PI3K/AKT/mTOR pathway, cancer mortality, dietary restriction, autophagy, translational regulation, survival analysis
- MeSH terms
- Administration, Oral, Aging, Animals, Carrier Proteins, Diet, Disease Susceptibility, Female, Longevity, Male, Specific Pathogen-Free Organisms, Time Factors, Survival Analysis, Phosphotransferases (Alcohol Group Acceptor), Sirolimus, Mice, TOR Serine-Threonine Kinases
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