Aging
Conditions
Keywords
Aging, Reverse Aging, Rapamycin, Biological Age, Chronological Age, Prolon
Brief summary
Aging can be defined as a time-dependent functional decline in physiological function, which may increase the vulnerability to diseases and eventually death. The question is whether aging is a normal process, or exists as an "uber-illness?" Work done by Dr Sinclair at Harvard suggests the latter. Dr. Sinclair feels people should be able to age-in-place, or even reverse age. Aging is arguably the single biggest risk factor for all acquired and chronic diseases. Delaying the aging rate by 7 years would cut the incidence of chronic disease in half! Up until know the effects of anti-aging would need longitudinal studies until death. Now, with the advent of a 3rd generation OMIC Age clock, there is a way to assess if an intervention is changing the rate of aging and other methylation patterns associated with aging.
Interventions
10 mg initial bolus dose of rapamycin followed by a weekly 6 mg rapamycin
DIETARY_SUPPLEMENTProlon diet
Prolon 5-day diet at 0, 1, 2, 3, 4,and 5 months
Sponsors
The Christ Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects will be healthy and of any sex, any ethnicity, and any age from 50 to 80 * "Healthy" subjects will be defined as a real-world cohort of individuals likely to utilize such an intervention * May be on other medications if they do not conflict with rapamycin. * All medical conditions need to be stable and well controlled. * Willing and able to provide informed consent
Exclusion criteria
* Severe illnesses, for which rapamycin may cause harm. This would not be limited to but include active neoplastic or auto-immune disease. If patients have a previous history of cancer or auto-immune disease, the risks and benefits and possible adverse reactions will be discussed at time of consent * History of organ transplant * Any unstable medical condition that would interfere with the study * Hepatic impairment. Note: Patients with elevated liver enzymes and low albumin, will be further screened for hepatic impairment. Elevated liver enzymes \< 2x upper limit of normal will not be considered hepatic impairment. * Renal impairment, indicated by a serum creatinine \> 1.4 mg/dL * Anemia indicated by a hemoglobin \< 12 g/dL * Platelets \< 80,000/cumm, * ANC \< 1,000 / cumm * Total WBC \< 3,000/cumm * Pregnancy or breastfeeding or woman of childbearing potential with inadequate contraception * Unstable mental illness * A condition where rapamycin may interfere deleteriously with a medication that is taken by a potential subject * Currently prescribed with high dose CYP3A4 pathway medications such as verapamil \> 240 mg; simvastatin \>40 mg, lovastatin \> 40 mg or atorvastatin \> 40 mg daily. Poor GI motility as demonstrated by delayed gastric emptying on a radionucleotide isotope scan. * Intercurrent severe infection at initiation of study drug * Any and all other reasons that the investigator may determine that the participant is not suitable for study enrollment. * History of or active eating disorders as deemed by PI. * BMI lower than 18.5 * Any medication that may dangerously lower glucose while on the FMD. This will include insulin, sulfonylureas (glyburide; glipizide); Thiazolidenediones ( eg piogltazone; rosiglitazone); GLP1 drugs (semaglutide; tirzepatide);; DPP-4 inhibitors (eg sitagliptin; saxagliptin); Alpha -glucosidase inhibitors (acarbose; miglitol). Patients on SGLT2 inhibitors (empagliflozin; canagliflozin) and Metformin (glucophage) may be included in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Biological Age from Baseline to End of Study based on Tru Diagnostic Tru Age OMICm Age test results. | 24 weeks | To evaluate the gradated effects of mTOR inhibition on a new OMIC methylation test that evaluates biological (vs chronological) age over a six-month period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To evaluate the effects of AMPK (AMP Kinase inhibition) on aging. Change in OMICm methylation from baseline to Week 24 based on Tru Diagnostic Tru Age OMICm Age test results. | 24 weeks | . This will duplicate studies already done utilizing a 5 day Fasting Mimicking Diet (FMD) (Prolon) on aging. The FMD diet will be administered 6 times - at monthly intervals. Change in OMICm methylation from baseline to Week 24 |
| Effect of weekly low-dose rapamycin on aging based on Tru Diagnostic Tru Age OMICm Age test results. | 24 weeks | Change in OMICm methylation from baseline to Week 24 |
| Lowering of insulin resistance based on Tru Diagnostic Tru Age OMICm Age test results. | 24 weeks | To evaluate the combined effects of AMPK and low-dose weekly rapamycin, at lowering insulin resistance, and thereby PI3K (PI3 kinase). |
| Effects on insulin resistance | 24 weeks | To stratify outcomes of the prior three outcomes based on insulin resistance. This will be monitored using a Quest Lab Insulin Resistance panel to determine if insulin resistance is a confounding variable from any of the above. Variability of results in a, b, or c based on high, low or moderate insulin resistance. |
| Does reversal of age improve cognition based on the Cognitive Flexibility Inventory. | 24 weeks | Changes in the Cognitive Flexibility Inventory from baseline to week 24. Scores range from 20-140, with a higher score representing a better outcome. |
| Patterns based on Age based on Tru Diagnostic Tru Age OMICm Age test results. | 24 weeks | To see if any pattern exists within age group categories. (50-65; older than age 65). Change in OMICm methylation results from baseline to Week 24 by two sub populations: ages 50-65 and ages older than age 65 |
| Sex Difference based on Tru Diagnostic Tru Age OMICm Age test results. | 24 weeks | Change in OMICm methylation from baseline to Week 24 by male vs female |
| Safety and tolerability of rapamycin and Prolon | 28 weeks | Review of adverse reactions from baseline to Week 28 |
Countries
United States
Outcome results
None listed