China is currently in an accelerated stage of population aging, and brain diseases pose a significant threat to the health of the elderly. " Preventing brain aging and maintaining brain health" has become a high-level goal of healthy aging. During the process of aging, the physiological and psychological states of elderly people change, making them prone to nervousness and exhaustion, which can disturb the brain spirit, damage the brain collaterals, and severely endanger brain health. Starting from the holistic view of cultivating both body and spirit in traditional Chinese medicine, based on the physical and mental characteristics of the elderly, this paper applies the concept and method of " relaxation and tranquility" in the protection of elderly brain health, focusing on maintaining relaxation and tranquility in both physical and mental aspects. Specific measures include emphasizing subjective consciousness, relaxing the heart and calming down; utilizing the daoyin method, relaxing the body and calming down, combining relaxation and tranquility, cultivating both body and spirit to prevent diseases and protect the brain, which enables the elderly to have a healthy mind and body, a sense of happiness and fulfillment, and to age gracefully. Simultaneously, advocating for tranquility is also called " respect" for relaxation, following nature to understand constant changes, and improving one′s ability to think positively in old age, in order to expand ideas for the protection of elderly brain health.

AIM:To investigate the regulatory mechanism of silent information regulator 6(Sirt6)on nuclear factor E2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)signaling pathway and ferroptosis in skeletal muscle aging in-duced by D-galactose(D-Gal)in mice.METHODS:A D-Gal-induced mouse aging model was established and randomly divided into control and D-Gal groups.In vitro,D-Gal-treated C2C12 mouse myoblasts were treated with ferroptosis ago-nist erastin(Era)and inhibitor ferrostatin-1(Fer-1),Sirt6 agonist MDL-800 and inhibitor OSS-128167,and Nrf2 siRNA.Mouse body weight and forelimb relative grip strength were monitored.RT-qPCR and Western blot were used to measure the expression of Sirt6,Nrf2,HO-1,P53,P21,P16,muscle ring finger protein 1,muscle atrophy F-box,solute carrier family 7 member 11,and glutathione peroxidase 4 in gastrocnemius muscle and myoblasts.Hematoxylin-eosin staining was performed to examine muscle fiber diameter.Levels of reactive oxygen species(ROS),mitochondrial ROS,mitochon-drial membrane potential,senescence-associated β-galactosidase activity,glutathione,lipid peroxidation,and Fe2? con-centration were measured in myoblasts and myotubes.Immunofluorescence staining was used to detect myosin heavy chain(MyHC)expression in myotubes.RESULTS:Mice in the D-Gal group exhibited significant reductions in body weight and forelimb grip strength(P<0.01),upregulation of aging and muscle atrophy markers,and decreased mRNA and pro-tein levels of ferroptosis markers and Sirt6(P<0.01).Additionally,gastrocnemius muscle fiber diameter significantly de-creased(P<0.01).In D-Gal-treated myoblasts and myotubes,aging and muscle atrophy markers were elevated(P<0.01),MyHC expression was reduced,and protein levels of ferroptosis-related markers,Sirt6,Nrf2,and HO-1 were de-creased(P<0.05 or P<0.01).Fer-1 pre-treatment alleviated these changes(P<0.05 or P<0.01).MDL-800 significantly improved D-Gal-induced aging and muscle atrophy in myoblasts and myotubes,while increasing the expression of ferropto-sis-related proteins(P<0.05 or P<0.01).However,the addition of Erastin abolished the beneficial effects of MDL-800(P<0.05 or P<0.01).Following Nrf2 siRNA transfection,the ability of MDL-800 to improve ferroptosis and the quality of myotube formation was significantly diminished(P<0.05 or P<0.01).CONCLUSION:Sirt6 inhibits ferroptosis in myo-blasts through the Nrf2/HO-1 signaling pathway,thereby alleviating age-related changes in myoblasts and the decline in myotube formation quality,which is beneficial for improving skeletal muscle aging.

AIM:To investigate the regulatory mechanism of silent information regulator 6(Sirt6)on nuclear factor E2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)signaling pathway and ferroptosis in skeletal muscle aging in-duced by D-galactose(D-Gal)in mice.METHODS:A D-Gal-induced mouse aging model was established and randomly divided into control and D-Gal groups.In vitro,D-Gal-treated C2C12 mouse myoblasts were treated with ferroptosis ago-nist erastin(Era)and inhibitor ferrostatin-1(Fer-1),Sirt6 agonist MDL-800 and inhibitor OSS-128167,and Nrf2 siRNA.Mouse body weight and forelimb relative grip strength were monitored.RT-qPCR and Western blot were used to measure the expression of Sirt6,Nrf2,HO-1,P53,P21,P16,muscle ring finger protein 1,muscle atrophy F-box,solute carrier family 7 member 11,and glutathione peroxidase 4 in gastrocnemius muscle and myoblasts.Hematoxylin-eosin staining was performed to examine muscle fiber diameter.Levels of reactive oxygen species(ROS),mitochondrial ROS,mitochon-drial membrane potential,senescence-associated β-galactosidase activity,glutathione,lipid peroxidation,and Fe2? con-centration were measured in myoblasts and myotubes.Immunofluorescence staining was used to detect myosin heavy chain(MyHC)expression in myotubes.RESULTS:Mice in the D-Gal group exhibited significant reductions in body weight and forelimb grip strength(P<0.01),upregulation of aging and muscle atrophy markers,and decreased mRNA and pro-tein levels of ferroptosis markers and Sirt6(P<0.01).Additionally,gastrocnemius muscle fiber diameter significantly de-creased(P<0.01).In D-Gal-treated myoblasts and myotubes,aging and muscle atrophy markers were elevated(P<0.01),MyHC expression was reduced,and protein levels of ferroptosis-related markers,Sirt6,Nrf2,and HO-1 were de-creased(P<0.05 or P<0.01).Fer-1 pre-treatment alleviated these changes(P<0.05 or P<0.01).MDL-800 significantly improved D-Gal-induced aging and muscle atrophy in myoblasts and myotubes,while increasing the expression of ferropto-sis-related proteins(P<0.05 or P<0.01).However,the addition of Erastin abolished the beneficial effects of MDL-800(P<0.05 or P<0.01).Following Nrf2 siRNA transfection,the ability of MDL-800 to improve ferroptosis and the quality of myotube formation was significantly diminished(P<0.05 or P<0.01).CONCLUSION:Sirt6 inhibits ferroptosis in myo-blasts through the Nrf2/HO-1 signaling pathway,thereby alleviating age-related changes in myoblasts and the decline in myotube formation quality,which is beneficial for improving skeletal muscle aging.